SPECIAL LECTURE AND PLENARY ABSTRACTS – No. 1 – 6
TOPICAL SEMINAR ABSTRACTS – No. 7 – 41
POSTER ABSTRACTS – No. 42 – 1133
(Poster abstracts are listed in orderof the scientific programme so do not run in numerical
sequence)
1
Ulf Lindblom Special Lecture:
BASIC SCIENCE AND MECHANISMS OF VISCERAL PAIN
F. Cervero
The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada
Visceral pain is an important component of the normal sensory repertoire of all human beings and a
prominent symptom of many clinical conditions. Visceral pain is also one of the most frequent reasons
for patients to seek medical attention. However, many practitioners regard visceral pain as only a
symptom of the underlying disease that will go away once the disease is cured. Also, much of what
we know about the basic mechanisms of pain derives from experimental studies of somatic
nociception. Even chronic pain models are generally based on inflammatory lesions of the skin,
muscles or joints or on peripheral nerve injuries and therefore pain of internal origin, or visceral pain,
is a subject of lesser interest.
Yet, it is now quite clear that different forms of pain are mediated by different neurological
mechanisms so that it is no longer possible to maintain a view of the pain system as a simple alarm
device with a single, unique organization. The study of visceral pain can offer insights into the
workings of the brain that may be complementary to what we know from studies of somatic or
neuropathic pain. Also, the treatment of some forms of visceral pain is now oriented more towards the
neurological system that mediates the pain than towards the underlying disease of the visceral organ.
This is particularly relevant in conditions such as the irritable bowel syndrome where treatment is
often directed to the nervous system rather than to the gastrointestinal tract.
Visceral nociception generates increases in pain sensitivity in locations remote from a diseased
organ. Referred hyperalgesia is also present in functional pain states without apparent damage of an
internal organ. These changes may be due to sensitization of peripheral nociceptors, to excitability
changes of spinal cord neurons or to variations in descending control of spinal transmission.
Sensitization of visceral nociceptors is influenced by the microenvironment where the nociceptors are
located and the function of non-neural epithelial cells of the organ in question. The importance of the
GABAergic system in spinal nociceptive processing has also been appreciated but we have only
recently begun to understand how this system is modulated by the regulation of anion gradients. Also,
hormonal dysfunction can contribute to generate visceral hyperalgesic states as shown in models of
functional abdominal pain disorders that are estrogen-dependent.
2
THINKING PAIN: EXPOSING THE BRAIN ARCHITECTURE OF PAIN MOTIVATION
1,2
B. Seymour
1
2
University of Cambridge, Cambridge, UK, Center for Information and Neural Networks, National
Institite for Information and Communications Technology, Osaka, Japan
Computational neuroscience aims to determine how the brain implements information processing
operations that ultimately give rise to behaviour. Such an approach can be applied to pain to give a
mechanistic account of the specific underlying functions that are achieved by the pain system. The
attractiveness of this is that it frees us from an approach bound to phenomenonology, and provides a
quantitative framework for interrogating neurophysiological data based on what the brain actually
does - which is process information.
Here I will consider the motivational function of pain, which concerns how the brain uses nociceptive
information to shape future behaviour away from harm. This is informed by a rich literature from
experimental psychology, in the domain of Palvovian and instrumental conditioning. This literature
describes the distinct processes employed by animals and humans as they learn about their world
through interacting with it, and use this information to optimize future behaviour. In particular, this
invokes both aversive and appetitive learning systems that learn the value of actions and states, in
terms of the prospects of punishments (such as pain) and rewards. From a computational
perspective, these processes can be easily formalized as control theoretic problems, for instance as
pain minimization and reward maximization. Such a formalisation provides powerful insights into
putative algorithmic processes that the brain might actually implement to solve them.
I will show evidence that suggests that a particular class of learning algorithm - called Reinforcement
Learning - is implemented in the brain as it learns about pain. I will present data from a series of
Palvovian and instrumental learning experiments in humans, studied using functional brain imaging,
that reveal an aversive learning system centered on the ventral and dorsal striatum, which computes
the prediction errors that allow the values of states and actions to be efficiently learned. I will also
illustrate how these aversive processes interact with reward learning systems. This is manifest as an
opponent, inhibitory interaction in the case of Pavlovian (state) learning, but as a competitive
interaction in the case of instrumental pain avoidance. These findings provide a basic, working
neurobiological account of pain-related prediction and decision-making - the core components of pain
motivation.
3
TRANSLATING SCIENCE INTO TREATMENT: THE EXAMPLE OF VISCERAL PAIN
Q. Aziz
Wingate Institute of Neurogastroenterology, Barts and The London School of Medicine and Dentistry,
Queen Mary University of London, London, UK
Tissue damage due to inflammation/injury leads to sensitisation of primary afferent nerves (peripheral
sensitisation) due to the release of inflammatory mediators which reduce the transduction threshold of
primary afferents and recruit previously silent nociceptors. A consequence of peripheral sensitisation
is the development of an area of pain hypersensitivity in the surrounding uninjured tissue (secondary
hyperalgesia) due to increased sensitivity of spinal dorsal horn neurons. This central sensitization is
sustained by phosphorylation of N-Methyl-D-Aspartate (NMDA) receptors expressed in dorsal horn
neurones, which increases receptor sensitivity to synaptically released glutamate.
Human model of visceral hypersensitivity: It has been demonstrated that infusion of hydrochloric acid
into the healthy oesophagus reduces the pain threshold not only in the acid exposed region
(peripheral sensitization) but also in the adjacent unexposed region (central sensitisation). This
oesophageal hypersensitivity is long lasting (up to 5 hours after 30 minutes of acid) (1). Furthermore,
patients with unexplained chest pain demonstrate oesophageal hypersensitivity to electrical
stimulation irrespective of the presence or absence of oesophagitis or gastrooesophageal reflux.
However in response to acid infusion, patients without evidence of oesophagitis or gastrooesophageal reflux demonstrate heightened oesophageal hypersensitivity, in contrast those with
oesophagitis or gastro-oesophageal reflux fail to demonstrate any further increase in hypersensitivity.
This suggests that in the former case oesophageal hypersensitivity is either a manifestation of
hypervigilance or partially sensitized afferent pathways. In contrast in the latter case injury may have
led to maximal peripheral/central sensitisation (ceiling effect) and hence further acid infusion was
unable to induce further sensitisation.
Pharmacological profiling of visceral hypersensitivity: Pharmacological profiling of this model of
oesophageal hypersensitivity has been performed to further explore the underlying mechanisms of
peripheral and central sensitization. Using a prostanoid receptor (EP) 1 receptor antagonist which
blocks the prostaglandin receptor E2 (PGE2) (2), Ketamine an NMDA receptor antagonist (3) and
Pregabalin an alpha 2 delta ligand (4) it has been demonstrated that development of visceral
hypersensitivity in the healthy human oesophagus in response to acid infusion can indeed be
prevented by the use of both the EP1 and NMDA receptor antagonists. Because PGE2 receptors are
present on both primary afferents and spinal cord neurons it is possible that receptor antagonism at
both sites influenced visceral hypersensitivity in the model In contrast, because NMDA receptors are
located primarily in the central nervous system, and it is plausible that central sensitisation plays an
important mediating role.
These studies raise the intriguing possibility that if it were possible to identify patients with visceral
hypersensitivity due to peripheral / central sensitisation rather than due to hypervigilance then it may
be possible to treat them effectively with drugs that block specific receptors.
References:
1. Sarkar et al. Lancet 2000;356(9236):1154-1159.
2. Sarkar et al. Gastroenterology 2003;124(1):18-25.
3. Willert et al. Gastroenterology 2004
4. Chua YC, et al . Aliment Pharmacol Ther. 2012 Feb;35(3):319-26.
4
David Niv Special Lecture:
THE BRAIN AND THE OPIOIDERGIC SYSTEM
T. Tölle
Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum, Klinikum rechts der Isar der Technischen
Universität München, München, Germany
Opioids are believed to be mainstay in the treatment of pain, at least in the opinion of doctors and
patients. This derives from the centuries-old observation that they can effectively reduce pain as a
pharmacological tool, and, moreover that an highly effective system of endogenous pain control has
evolved within evolution which is termed the endogenous opioidergig pain control system.
Opioid receptors were first demonstrated in the central nervous system by radioligand binding
techniques in the rodent brain in the 1970s. Until recently, the characterization of the opioid receptor
system was restricted to animal models or human post-mortem tissue investigations. With the advent
of state-of-the-art opioid receptor ligand-PET techniques, the opioid receptor system is increasingly
being studied in vivo. On the level of receptor expression, ligand-PET is capable of delineating
neurochemical pathologies. Recent developments promise that ligand-PET will also allow us to
characterize dynamic short-term changes in neurotransmission.
With respect to pain, ligand-PET studies in the human CNS have already added tremendously to the
understanding of (patho-)physiology on the receptor level. However, up to now the armamentarium of
PET ligands to study the diversity of opioid receptors is rather incomplete and - in advanced PET
techniques - there is a lack in understanding of the basic mechanisms of “ligand activation”. Currently,
it is assumed that short-term changes in PET ligand binding might be related to competition of the
endogenous transmitter with the radiolabelled ligand. However, the origin of endogenous opioidergic
ligands to be released in distinct brain areas is still a matter of debate. Thus, there is a strong need for
further systematic investigations. As one possible approach, questions can be taken back to “goldstandard” tissue-bound pharmacological studies, in which expression and modulation of receptors
and endogenous ligands can be studied to test hypotheses driven by in vivo PET results. This will
allow to optimize PET-ligands in terms of affinity, specificity and intrinsic pharmacological activity and
to modify PET modelling algorithms to depict the functioning of opioid receptors in vivo.
Many PET and fMRI studies give a good example for the advances made in in vivo opioid receptor
imaging and in targeting the neurochemistry of pain.
The advantages of receptor ligand-PET imaging are remarkable, but nevertheless we have just
started using the potentials of this and other modern imaging techniques. Therefore, further
systematic research with this attractive techniques is needed to give more insights into the
pharmacology of pain.
5
THE MONOAMINERGIC SYSTEMS IN PAIN: FROM TREATMENTS TO COMORBIDITIES
M. Barrot, I. Yalcin
Institut des Neurosciences Cellulaires et Intégratives, UPR 3212 CNRS, Strasbourg, France
The noradrenergic and the dopaminergic systems exert major neuromodulatory influence on the
nervous system. This lecture will present recent progresses on their role in the therapeutic action of
antidepressant drugs in neuropathic pain, on their alteration in a chronic pain state and on the
influence it may have on the addictive potential of opioid pain-killers and on the cognitive and/or
anxiodepressive consequences of chronic pain. Antidepressant drugs are first-line treatments for
neuropathic pain. While their clinical efficacy was established more than 30 years ago, the underlying
mechanism still remains elusive. During the past 7 years, we developed researches to decipher it, by
identifying required receptors, neuroanatomical and cellular substrates and molecular actors. A new
mechanism is proposed in which antidepressant-recruited noradrenaline selectively acts through
beta2-adrenoceptors to relieve neuropathic allodynia by a peripheral anti-TNFα action. These findings
raise the question of the respective influence of beta-mimetics and beta-blockers in various chronic
pain states. Opioids are also useful for pain management, but their abuse potential is limiting their
regular use for chronic noncancer pain. Recently, new knowledge was obtained on the mechanism by
which opioids recruit the dopaminergic system which is critical for motivated behaviors, and preclinical
studies of the past decade started to address the complex interaction between opioid pain relief and
abuse potential. A newly defined brain region, the tVTA (tail of the ventral tegmental area), was
evidenced as primary neuroanatomical target for opioid recruitment of dopamine systems, thus
leading to an update of the classical disinhibition model. Different research groups also obtained
preclinical evidences that are supportive of altered rewarding properties of opioids in chronic pain
states. These promising works should foster interactions between clinicians and basic researchers to
promote progress regarding the question of opioid abuse in a pain context. Patients suffering from
chronic pain frequently have cognitive complaints and/or present mood disorders such as depression
and anxiety. However, the mechanisms underlying these comorbidities remain unclear. In the past
few years, major progress was done to preclinically model the cognitive and the anxiodepressive
consequences of chronic pain. As a result, researchers are now gaining insights into the
anatomomolecular mechanisms that are implicated. These recent findings are revealing a cortical
dissociation between various aspects of chronic pain, and modifications of the ascending
noradrenergic pathways arising from the locus coeruleus. Overall, these recent research
developments are shedding new light on the participation of monoaminergic systems in chronic pain
and its treatment.
6
MANAGEMENT CHALLENGE: THE COMORBIDITIES OF PAIN
1
1
M.A. Giamberardino , G. Affaitati , R. Costantini
1
2
2
Ce.S.I. 'G. D'Annunzio' University Foundation, Institute of Surgical Pathology, 'G. D'Annunzio'
University, Chieti, Italy
Multiple concomitant pain and nonpain conditions in the same patient are increasingly observed in the
clinical setting also in relation to the progressive aging of the population. Myofascial pain syndromes
from trigger points significantly co-exist with headache, fibromyalgia and a number of visceral pains.
Headache significantly co-occurs with fibromyalgia, dysmenorrhea, endometriosis or irritable bowel
syndrome, with epidemiological findings suggesting that the presence of comorbid pain conditions
may impact on the transition of episodic to chronic headache. Different visceral pain diseases also
frequently co-exist in the same patient, as in the case of ischemic heart disease and biliary calculosis
or endometriosis and urinary pains. These comorbidities may significantly influence each other, with
trigger points exacerbating headache and fibromyalgia or two visceral pains enhancing each other
when originating from organs sharing at least part of their central sensory projection (viscero-visceral
hyperalgesia). In comorbidities involving other medical, not necessarily painful, conditions there may
be important symptom interactions and/or implications for diagnosis and therapy. Hypertension or
diabetes can decrease or cancel pain perception from various algogenic comorbidities, e.g., painless
myocardial infarction, thus delaying their identification and treatment. Cardiac conduction
disturbances or arrhythmias can limit the use of first line drug treatments for neuropathic pain, while a
concurrent cardiovascular disease may affect the therapeutic approach to migraine therapy with
voasoactive compounds. Obesity has been claimed as an important risk factor for the development of
certain pains, especially osteoarthritis and low back pain, and the co-occurrence of pain and
overweight/obesity has been shown to negatively affect the quality of life. Affective disorders - such as
depression or anxiety - also frequently accompany many forms of pain, requiring careful evaluation for
diagnosis of their primary or secondary nature and for integrated treatment. Comorbidity in pain may
thus involve increased or decreased pain perception and/or impact significantly on the diagnosis and
treatment of the patient. In recent years an increasing number of studies have addressed pain
interactions from multiple concurrent diseases, in both experimental and clinical models, with the aim
of better understanding pathophysiological mechanisms underlying the complexity due to
comorbidities. The presentation will focus on different clusters of pain and nonpain co-occurrences
and report on the major outcome of these studies as the basis for approaching the management
challenges of comorbidities.
References:
Giamberardino MA, Jensen TS (Eds.). Pain comorbidities: understanding and treating the complex
patient. IASP Press: Seattle, 2012, pp. 507.
Nobili A, Garattini S, Mannucci PM, Multiple diseases and polypharmacy in the elderly: challenges for
the internist of the third millennium Journal of Comorbidity. 2011;1:1-17.
7
ENDOGENOUS ANALGESIA: AN UPDATE
1,2
3
4
D. Yarnitsky , S. Marchand , A. Dahan , R.R. Nir
1
1,2
2
Neurology, Rambam Health Care Campus, Clinical Neurophysiology, Technion-Israel Institute of
3
Technology, Haifa, Israel, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC, Canada,
4
Anesthesiology, University of Leiden, Leiden, The Netherlands
This workshop will provide a comprehensive overview on current understanding, at human level, of
endogenous analgesia as expressed by the conditioned pain modulation (CPM) test paradigm. (i) We
will discuss is the specificities of the paradigms used to elicit the CPM, including properties of the teststimulus and conditioning-stimulus required to elicit the response. MR and ERP based imaging of this
process of pain modulation will be demonstrated. (ii) In regards to the mechanisms of pain modulation
expressed by the CPM paradigm, we will discuss the interactions with emotional and autonomic
factors, influence of sex hormones, and the interface with the placebo response. Further, the
influence of pharmacological agents such as opioids and ketamine will be reviewed. (iii) The clinical
application part will cover the current knowledge on relevancy of pain modulation, as expressed by
CPM, on the clinical pain phenotype, including prediction of future pain, prediction of response to
specific therapies, and the dynamics of change in CPM efficiency along with painful life events.
8
CANCER PAIN -THE PLACE OF INTERVENTIONS.
C. Wells
Pain Matters, Liverpool, UK
What is the place of interventional techniques for cancer pain in modern practice?
The WHO analgesic ladder algorithm is widely recognised and used in cancer pain treatment, but
does not succeed in relieving all pain. Evidence on the importance of a multidisciplinary and multidimensional approach is starting to accumulate. There is a need for a new algorithm including all
potential treatment modalities for the management of cancer pain.
Interventional procedures were originally developed to tackle intractable pain in cancer patients. They
were often the mainstay of managing pain in patients with advanced disease. The development of
palliative medicine as a speciality with better use of strong opioids (by the clock) and increasing
availability have led to a sharp decline in the use of these useful procedures.
Modern radiological imaging and precise technique in skilled hands have improved the success rates
as well as reducing major complications from these procedures and they should now be offered
appropriately rather than being only used as a last resort.
Dr Vissers will discuss a new algorithm for cancer pain, Dr Vadalouka will cover epidural and spinal
techniques, and Dr Bhaskar will address neuroablative procedures to relieve pain in cancer.
9
STRUCTURAL BRAIN IMAGING IN CHRONIC PAIN: JUST AN EPIPHENOMENON?
1
2
3,4
5
M. Moayedi , Y. Assaf , J.P. Lerch , A. May , K.D. Davis
1
6,7,8
2
Neuroscience, Physiology and Pharmacology, University College London, London, UK, Department
of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel,
3
4
Neurosciences & Mental Health, The Hospital for Sick Children, Medical Biophysics, University of
5
Toronto, Toronto, ON, Canada, Institut fur systemische Neurowissenschaften, Universitatsklinikum
6
Hamburg Eppendorf, Hamburg, Germany, Brain, Imaging and Behaviour, Toronto Western Research
7
8
Institute, University Health Network, Institute of Medical Sciences, Surgery, University of Toronto,
Toronto, ON, Canada
Structural magnetic resonance imaging (sMRI) techniques are becoming increasingly popular in pain
research. Two modalities are used to evaluate brain structure: gray matter imaging and white matter
imaging. The main methods used to evaluate brain structure include voxel-based morphometry
(VBM), cortical thickness analysis (CTA), deformation-based morphometry (DBM) and diffusionweighted imaging (DWI). These methods have demonstrated that there are indeed structural brain
abnormalities in chronic pain, and that in some cases some of these abnormalities can be reversed
upon successful resolution of pain. However, the time-scale as well as the cellular and molecular
bases of changes in structural indices remain elusive.
The purpose of the workshop is to discuss findings of structural abnormalities in various chronic pain
conditions, and how these findings have informed our thinking about mechanisms of chronic pain.
Specifically, the talks will focus on (1) providing an overview of the various methods available for
analysis, (2) providing a summary of findings of structural abnormalities in various conditions, (3)
highlighting recent advances in characterizing the cellular and molecular underpinnings of structural
changes and/or abnormalities in chronic pain conditions, and (4) discussing issues that need to be
considered when performing structural brain analysis in chronic pain. The workshop will also discuss
the putative functional significance of structural brain abnormalities in chronic pain. Finally, we will
assess the advantages and disadvantages of structural brain imaging in chronic pain.
10
BRAIN MECHANISM UNDERLYING THE PAIN-REWARD INTERACTION
1,2
3
S. Becker , D. Talmi , B. Seymour
1
4
2
Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada, Department
of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Mannheim, Germany,
3
4
School of Psychological Sciences, University of Manchester, Manchester, UK, Center for
Information and Neural Networks, National Institite for Information and Communications Technology,
Osaka, Japan
Pain and reward are opponent processes but recent evidence suggests that their processing is
closely related. For example, reward and pain influence each other and interact, affecting e.g. goaldirected behavior and learning. Moreover, central processing of pain and reward overlap
neuroanatomically and neurochemically. However, surprisingly little is known about mediating brain
mechanisms. This workshop will address such brain mechanisms underlying the effects of pain and
reward on each other, decision-making and goal-directed behavior as well as reward-dependent
learning. The speakers will present and discuss evidence on dopamine's and serotonin's role in
mediating pain-reward interactions as well as implicated brain regions and electrocortical responses.
Dopamine is key in reward processing and has also been found to be relevant in pain. In the painreward interaction, dopamine seems to bias an organism towards a decision in situations with
conflicting motivations, prioritizing these conflicting motivations. Although implicated in reward,
motivation, and pain, the role of serotonin is less clear. Novel evidence indicates a selective
modulation of reward value by serotonin. Neuroanatomically, evidence cumulates that suggests
particular important roles of ventral striatum, anterior cingulate cortex (ACC) and prefrontal cortex in
mediating pain-reward interactions in different contexts. In particular, Feedback-Related Negativity as
an electrocortical response indicating prediction error has been shown to be similar between reward
and pain conditions in the ACC, suggesting common underlying mechanisms. Understanding the
brain mechanisms mediating pain-reward interactions is of crucial importance and clinically relevant
as, for example, reward-dependent decision-making and learning are impaired in chronic pain
patients.
11
RECENT ADVANCES IN ASSESSMENT, MANAGEMENT AND CLARIFICATION OF
UNDERLYING MECHANISMS OF CHRONIC OROFACIAL PAIN CONDITIONS
1
1
2
P. Svensson , I. Skyt , K. Iwata , B.J. Sessle
1
2
3
3
Aarhus University, Aarhus, Denmark, Nihon University School of Dentistry, Tokyo, Japan, Faculty
of Dentistry, University of Toronto, Toronto, ON, Canada
Some of the most common chronic pain conditions occur in the orofacial region and can present
diagnostic and management challenges to the clinician, especially because the aetiology and
pathogenesis of most of them are unclear. This Topical Seminar covers recent advances in our
understanding of mechanisms underlying the development and maintenance of chronic pain in the
orofacial region as well as recent advances in the assessment and management of these conditions.
Peter Svensson will review recent research from studies in humans that have applied assessment
techniques involving QST, brain imaging and other biomarkers for these conditions, as well as provide
details on recent studies of pharmacologic and non-pharmacologic approaches to manage them. Ina
Skyt will discuss the concept of perceptual distortion of the face in relation to orofacial pain and
present new data with experimental manipulation of the trigeminal nerves. Koichi Iwata will present
recent findings pointing to the involvement of non-neural (e.g. glia) as well as neural peripheral
processes in animal models of orofacial pain, and also point out emerging insights into some of the
molecular mechanisms involved. Barry Sessle will chair the Seminar as well as review recent findings
of processes that modulate trigeminal central sensitization following orofacial inflammation or nerve
injury in animals and that may explain some of the clinical findings in orofacial chronic pain states; he
will also present new findings of the effects on trigeminal central sensitization of recently introduced
drugs that may account for their clinical efficacy in the management of these conditions.
12
TRKA INHIBITORS FOR ITCH AND PAIN: DISEASE MECHANISMS AND CLINICAL EFFICACY IN
CHRONIC PRURITUS
1
2
P. Anand , C. Pincelli , D. Roblin
1
3
2
Imperial College London, London, UK, University of Modena and Reggio Emilia, Modena, Italy,
Creabilis SA, Luxembourg, Luxembourg
3
This workshop will describe the key role of TrkA in clinical itch and pain, and the successful translation
of TrkA inhibitor CT327 studies in animal models and cultured human sensory neurons to
demonstration of clinical efficacy in chronic pruritus. Pruritus is a bothersome, debilitating symptom of
many diseases, with significant impact on quality of life.
The first speaker (CP) will review the role of NGF and its receptors, the high-affinity receptor TrkA,
and low-affinity p75, in cutaneous disease mechanisms. NGF produced by keratinocytes sensitizes
and stimulates the sprouting of nerve fibres via TrkA, and regulates expression of sensory
neuropeptides and receptors e.g. the capsaicin receptor TRPV1. Increased NGF mediated
neurogenic inflammation is involved in the pathogenesis of several inflammatory dermatoses with
associated itch symptoms, including psoriasis.
The second speaker (PA) will report that human DRG and skin showed intense TrkA-immunoreactivity
in small neuronal cell bodies and sub-epidermal nerve fibres. TrkA inhibitor CT327 produced doserelated inhibition of capsaicin responses in cultured human sensory neurons, but had no effect on
neurite lengths at these concentrations.
The third speaker (DR) will present a placebo-controlled study of topical CT327 administered to 160
patients with psoriasis for up to 8 weeks. There was a statistically significant and clinically meaningful
reduction of VAS for pruritus (60% reduction for lowest dose CT327, versus 20.4% for placebo, p<
0.05).
These findings indicate the prospect of effective and safe TrkA inhibitor topical treatment for
cutaneous hypersensitivity in clinical disorders.
13
OPIOID USE FOR PERSISTENT PAIN: A 21
1
2
3
ST
CENTURY PERSPECTIVE
C. Stannard , E. Kalso , R. Knaggs , D. Weisberg
1
4
2
Pain Clinic, Frenchay Hospital, Bristol, UK, Institute of Clinical Medicine, Helsinki University Central
3
Hospital, University of Helsinki, Helsinki, Finland, Department of Clinical Pharmacy, University of
4
Nottingham, Nottingham, UK, School of Medicine, Yale University, New Haven, CT, USA
The interpretation of opioid prescribing trends over the past decade is the subject of current
international debate. In the United States and Australia the increased prescribing of opioids has been
paralleled by problems of misuse and opioid related harms. Although similar trends in prescribing are
seen in Europe, the extent to which these drugs are misused is unknown but the prescription data
suggest that many patients may be taking opioids without clinical benefit.
Critical evaluation of the role of opioids in pain management underpins any discussion about
appropriate use and findings from the literature should be interpreted comparatively with data on longterm effectiveness of other classes of medicine used for persistent pain. This session will explore a
contemporary analysis of published data on the effectiveness of opioids, will describe what is currently
known about opioid related harms in the UK and elsewhere in Europe and will present detailed
prescribing data from the UK from which we can learn much more about the clinical picture of opioid
use. The final presentation will explore some potential societal influences on opioid prescribing and
opioid related harms.
The session will conclude with a facilitated discussion to develop future strategies to ensure that
opioid therapy remains available for those patients in whom opioids support long term management of
pain, and how to minimise opioid exposure and associated harms in patients who achieve no lasting
benefit from the drugs.
14
PHANTOM LIMB PAIN: PREVENTION, TREATMENT AND NEUROPLASTICITY
1
2
3
L. Nikolajsen , T. Weiss , M. Diers
1
Danish Pain Research Center and Department of Anaesthesiology, Aarhus University Hospital,
2
Aarhus, Denmark, Biological and Clinical Psychology, Friedrich Schiller University Jena, Jena,
3
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical
Faculty Mannheim, Heidelberg University, Mannheim, Germany
Phantom limb pain (PLP) is common experience after an amputation and the treatment still represents
a major challenge.
In the first part of the symposium we will report about preamputation pain as a very consistent risk
factor for PLP, and a possible prevention of PLP by reducing pain before the amputation. An overview
of pharmacological randomized trials will be given and similarities to- and adaptations from other
neuropathic pain disorders will be discussed.
In the second part of the symposium we report on how stimulation of the stump (discrimination
training) and use of functional prostheses can reduce PLP. We investigated whether a coupling of the
two types of PLP treatment in form of prostheses with somatosensory feedback can further reduce
PLP. We demonstrate a significant increase of functionality of the prosthesis in everyday tasks
especially when handling soft and fragile objects and a reduction of PLP.
In the last part we will talk about how an amputation changes the body image and its representation in
the brain. We will show functional imaging data of several body illusions like the mirror box illusion or
the rubber hand illusion in amputees with and without PLP. The results will be discussed with regard
to the plasticity of the body image and its influence on PLP and treatment approaches.
Taken together this symposium will give a brief overview of prevention and treatment of PLP and it's
accompanying cortical changes.
15
NOVEL INSIGHTS INTO THE ROLE OF SYNAPTIC LONG-TERM POTENTIATION AND LONGTERM DEPRESSION IN NOCICEPTION AND PAIN
1
2
J. Sandkühler , H.U. Zeilhofer , W. Magerl
3
1
Dept. of Neurophysiology, Center for Brain Research, Medical University of Vienna, Vienna, Austria,
Institute of Pharmacology and Toxicology, University of Zurich, Institute of Pharmaceutical Sciences,
3
Swiss Federal Institute of Technology (ETH), Zürich, Switzerland, Dept. of Neurophysiology, Center
of Biomedicine and Medical Technology Univ Heidelberg, Mannheim, Germany
2
Long-term potentiation (LTP) and long-term depression (LTD) of nociceptive synaptic transmission
are central mechanisms controlling the gain of nociceptive processing up to the level of conscious
pain perception. The interaction of both elementary mechanisms allows for the bidirectional
modulation of nociceptive sensitivity. This symposium will highlight the latest findings in this fast
developing field of research in animals and humans. In particular we want to elucidate the impact of
endogenous pain control systems on nociceptive LTP and LTD mechanisms.
Jürgen Sandkühler will demonstrate the general utility of LTP-like nociceptive plasticity in controlling
the gain of spinal nociceptive transmission. He will highlight the role of the opioidergic system for
modification of nociceptive LTP. Hanns Ulrich Zeilhofer will present new findings on the impact of the
endogenous cannabinoid system on the balance between spinal nociceptive LTP and LTD. Walter
Magerl will extend the concepts of nociceptive LTP and LTD to the field of human pain plasticity. It will
be shown how temporal and spatial summation influences the balance between LTP and LTD of
human pain sensation. Pain-LTP can be acutely reversed by LTD-inducing stimulation. Moreover, it
will be demonstrated how the activation of endogenous pain control limits the expression of human
pain-LTP.
16
TOWARDS AN OBJECTIVE BRAIN MEASURE OF PAIN - ASSESSING THE MULTIVARIATE
REPRESENTATION OF PAIN
1
2
3
G. Iannetti , K. Wiech , M. Ploner
1
Department of Neuroscience, Physiology and Pharmacology, University College London, London,
3
FMRIB, University of Oxford, Oxford, UK, Department of Neurology, Technische Universität
München, Munich, Germany
2
Pain is a highly subjective experience that results from the interplay of somatosensory input and a
broad variety of contextual factors. Functional neuroimaging and electrophysiological studies have
shown that the complexity of the pain experience is associated with an extended network of brain
areas, which yields neuronal responses at different frequencies. It is, however, increasingly
recognised that most pain-related neuronal responses are not specific to pain. Instead there is
cumulating evidence suggesting that pain is subserved by complex spatial-temporal-spectral patterns
of brain activity, which can more adequately be assessed using multivariate approaches. The
proposed workshop will present the concept of a multivariate representation of pain in the human
brain and current approaches to investigate it. In three presentations, we will discuss the (i) limitations
of traditional approaches to identify the cerebral representation of pain, (ii) the principles of
multivariate analyses of pain processing in the brain, and (iii) first applications of multivariate analyses
to functional neuroimaging and electrophysiological data. We will discuss how multivariate analyses
extend current concepts of the representation of pain in the human brain, and highlight possible
applications of multivariate 'brain reading' approaches as neuronal markers of pain perception. The
workshop will, thus, highlight a cutting-edge concept of the cerebral representation of pain and
address a novel, timely and relevant topic that should be of interest to a broad audience of basic and
clinical scientists.
17
AGE-RELATED CHANGES IN PAIN PROCESSING: PSYCHOPHYSICAL FINDINGS AND
CLINICAL IMPLICATIONS
1
1
R.B. Fillingim , J.L. Riley , C.S. Nielsen
1
2
2
University of Florida, Gainesville, FL, USA, Norwegian University of Science and Technology,
Institute of Public Health, Oslo, Norway
The prevalence and severity of chronic pain increase with age, which represents a growing societal
concern due to the “graying” of Western populations. Thus, improved understanding of age-related
changes in pain processing is paramount. Previous experimental research provides conflicting
findings regarding age-related changes in pain perception, however, recent studies using more
sophisticated psychophysical approaches and larger sample sizes more consistently demonstrate
changes in pain modulatory function among older adults. This session will present data from three
different studies regarding age-related changes in pain modulation, and the clinical relevance thereof.
Dr. Joseph Riley will present results from a series of studies using dynamic psychophysical
approaches to assess pain facilitation and pain inhibition among healthy older versus younger adults.
These findings demonstrate an age-related shift in the pain modulatory balance toward relatively
greater pain facilitation. Dr. Christopher Nielsen will present findings from a large epidemiological
study in Norway that assessed experimental pain responses in more than 10,000 adults, including a
large cohort of older individuals, revealing complex associations of age and sex with pain sensitivity.
Dr. Roger Fillingim will moderate the session and will present findings from a study of older adults with
knee osteoarthritis (OA). These findings demonstrated that increased pain sensitivity and pain
facilitation were associated with increased severity of knee OA symptoms. Taken together, the
findings suggest that aging is associated with changes in pain modulatory function characterized by
increased pain facilitation and diminished pain inhibition, and that these changes may contribute to
age-related increases in clinical pain symptoms.
18
EVIDENCE AND FUTURE ROLE OF SPINAL INTERVENTIONAL PAIN MANAGEMENT
1
2
S. Erdine , B. Morlion , M. van Kleef
1
3,4
2
Algology, Istanbul Pain Center, Istanbul, Turkey, Leuven Centre for Algology & Pain Management,
3
University Hospitals Leuven, Leuven, Belgium, Dpt of Anaesthesiology and Pain Management,
4
Maastricht, Free University of Amsterdam, Amsterdam, The Netherlands
What is the Relevance of Diagnostic Blocks for Spinal Interventions?
Interventional Procedures for Spinal Pain: Latest Evidence
Misuse and Abuse of Inerventional Pain Management
Most interventional pain management (IPM) procedures are not supported by solid evidence. Indeed,
a continued lack of well-designed, prospective, randomized, placebo-controlled trials evaluating IPM
for chronic spinal pain persists, mostly because of methodological issues of patient selection by
diagnostic blocks. The use of diagnostic test blocks to predict outcome of interventional procedures is
debated because of the high rate of false positive tests. Therefore, patient selection for specific
treatments for spinal pain based on diagnostic test blocks remains a critical and methodological issue
in the treatment of spinal and further studies are needed.
In this topical seminar evidence based studies for interventional pain procedure on cervical, thoracic
and lumbar areas will be presented.
Recommendations formulated are based on “Grading strength of recommendations and quality of
evidence in clinical guidelines” described by Guyatt et al. and adapted by van Kleef et al. Since the
introduction of interventional pain procedures by the 80's, Interventional techniques are performed by
physicians in multiple specialties, in various settings, with are numerous variabilities across the world.
There is an enormous amount of increase using the IPM procedures which we have to seriously
consider the misuse and abuse of these procedures.
The future of IPM requires a proper understanding of the practice of IPM, the appropriate use of
interventional techniques, the research aimed at elucidating the pathophysiologic basis of pain, the
studies validating evidence-based approaches for IPM, and the good faith effort to eliminate fraud and
abuse with contained and appropriate utilization.
19
TRANSLATIONAL STUDIES ON NERVE GROWTH FACTOR, SENSITISATION AND PAIN
1
2
T. Graven-Nielsen , M. Schmelz , S. Mense
1
3
2
Center for Sensory-Motor Interaction (SMI), Aalborg University, Aalborg, Denmark, Dept.
3
Anesthesiology, University Heidelberg, Heidelberg University, Medical Faculty Mannheim CBTM,
Mannheim, Germany
Musculoskeletal structures are significant sources of chronic pain. New models and systematic
approaches to study mechanisms and manifestations of sensitisation in musculoskeletal pain are
needed to improve diagnosis and therapy. Nerve growth factor (NGF) has been identified as clinically
relevant mediator for peripheral and central sensitisation. Intracutaneous injection of NGF in humans
causes long lasting mechanical and heat hyperalgesia without any visible signs of inflammation. While
heat hyperalgesia occurs by hours after the injection mechanical hyperalgesia is detected with a delay
of some days and reaches a maximum 2-3 weeks after the injection. The duration of mechanical
hyperalgesia reaches about 8 weeks. Interestingly, the sensitisation is restricted to the injection site
and therefore appears to be primarily of peripheral origin. In contrast, injection of the same amount of
NGF into the muscle fascia causes mechanical hyperalgesia for only about 2 weeks. Intramuscular
injections of NGF in humans induce widespread mechanical hyperalgesia and even facilitated central
mechanisms such as temporal summation of pain and referred pain. Basic animal data have shown
immediate peripheral sensitisation and hyperexcitability of dorsal horn neurons after minutes to hours.
Repeated intramuscular NGF injections within days caused an even more pronounced central
sensitisation in animals and progressively increased soreness in humans. Translation of experimental
NGF sensitisation from animal to human and back-translation from successful clinical anti-NGF trials
into experimental models launch new ways to identify pathophysiology in musculoskeletal
hyperalgesia and confirm the implication of NGF in musculoskeletal pain.
20
UNRAVELLING PAIN IN CHRONIC PANCREATITIS
1
2
3
A. Drewes , J.B. Frøkjær , O.H.G. Wilder-Smith , S. Olesen
1
1
2
Mech-Sense, Department of Gastroenterology and Hepatology, Mech-Sense, Department of
3
Radiology, Aalborg University Hospital, Aalborg, Denmark, Radboud University Medical Centre,
Nijmegen, The Netherlands
Intense visceral pain is a dominant feature of chronic pancreatitis and its treatment remains a major
clinical challenge. Basic studies of pancreatic nerves and experimental human pain research have
provided evidence that pain processing is abnormal in the patients and in many cases resembles that
seen in neuropathic pain disorders. Consequently, the management of pain by traditional methods
based on nociceptive deafferentation (e.g. surgery and visceral nerve blockade) becomes difficult and
often ineffective. This novel and improved understanding of pain aetiology requires a paradigm shift in
pain management of chronic pancreatitis. Modern mechanism based pain treatments taking into
account altered pain processing are likely to increasingly replace invasive therapies targeting the
nociceptive source, which should be reserved for special and carefully selected cases. The outline of
this topical seminar is to unravel pain mechanisms in chronic pancreatitis and based on this
knowledge propose novel options for pain treatment. An overview of the pain mechanisms underlying
pain in chronic pancreatitis with special emphasis on human experimental pain, including quantitative
sensory testing, advanced neurophysiological methods and modern imaging is provided. This is
followed by a discussion of pain treatment in chronic pancreatitis using the classical approach as well
as an update on new mechanisms based treatment strategies with special emphasis on pregabalin.
Finally a model to predict the effects of analgesics will be discussed.
21
PAIN AND PLACEBO IN DEMENTIA AND NORMAL AGING
1
2
M. Amanzio , M. Kunz , L. Vase
1
3
2
Department of Psychology, University of Turin, Turin, Italy, Department of Psychology, University of
3
Bamberg, Bamberg, Germany, Department of Psychology and Behavioural Sciences, University of
Aarhus, Aarhus, Denmark
Acute and chronic pain conditions are often present in elderly individuals, but only a small minority of
patients with dementia are prescribed analgesics and thus, these patients may be severely
undertreated for their pain. To further exacerbate the situation, even when patients with dementia
receive analgesic treatment, they have shown a reduced placebo analgesia effect and thereby a
reduced response to pain medication. Moreover, patients with Alzheimer's disease have been shown
to experience a significantly higher number of adverse events in relation to placebo treatment, which
further complicates the effective pain treatment.
Within this seminar, we want to give an overview on the challenges occurring when trying to assess
and treat pain in dementia.
In the first talk, Miriam Kunz will focus on why pain often remains undetected in patients with dementia
and present promising new pain assessment strategies, with a special focus on the facial expression
of pain.
Martina Amanzio will focus on placebo analgesia by giving an overview of how psychological and
neurophysiological elements of expectations may influence placebo analgesic responses in patients
with dementia and how to optimize the therapeutic context to achieve better outcomes.
In the last talk, Lene Vase will give an overview of how the level of cognitive impairment may influence
the frequency, type and potential mechanisms underlying the positive and negative outcome of
pharmacological treatment, with a special focus on whether patients' characteristics can be
meaningfully applied in therapies involving older populations.
22
PURINERGIC SIGNALING: A KEY MODULATOR OF NOCICEPTION AND A PROMISING
TARGET FOR ACUTE AND CHRONIC PAIN STATES
1
2
B. Sperlagh , E. Fabbretti , S. Ceruti
1
3
2
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary, Center for
3
Biomedical Sciences and Engineering, University of Nova Gorica, Vipava, Slovenia, Department of
Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
The discovery of new molecular players in pain transmission represents the turning point towards
success in the search for new and effective analgesics to fulfill the needs of patients still suffering
from currently incurable acute and, mostly, chronic pain states. A considerable amount of data has
accumulated over the last 20 years suggesting that the purinergic system indeed represents one of
these new and interesting actors. Extracellular adenine and uracil nucleotides are key signaling
molecules in the central and peripheral nervous system, and control a wide variety of physiological
processes through the activation of specific membrane receptors. Interestingly, their extracellular
concentrations rise significantly following tissue damage or inflammation, due to their massive release
from damaged or inflammatory cells or as co-transmitters from overactive neurons. Thus, nucleotides
might represent potential targets for the modulation of disease-associated symptoms, like pain, where
a strong integration between different cell types is expected. In this Topical Workshop, we will provide
an overview of the state-of-the-art on purinergic system in pain transmission, and on its future
exploitation towards new painkillers. In particular, we will focus: on the role of the G protein-coupled
P2Y12 receptor (the only nucleotide receptor currently targeted by the blockbuster anti-platelet drug
clopidogrel) in inflammatory and neuropathic pain; on the role of the most promising purinergic target,
the neuronal P2X3 channel, in chronic and visceral pain, and on the role of P2 receptors expressed
by glial cells in peripheral ganglia, as new targets for migraine and neuropathic pain.
23
VIRTUAL REALITY THERAPIES FOR PHANTOM LIMB PAIN
1
2
3
4,5
B.N. Perry , C. Mercier , S.R. Pettifer , J. Cole , J.W. Tsao
1
6,7
2
Rehabilitation, Walter Reed National Military Medical Center, Bethesda, MD, USA, CIRRIS, Laval
3
University, Quebec City, QC, Canada, School of Computer Science, University of Manchester,
4
5
Manchester, Clinical Neurophysiology, Poole Hospital, Poole, Clinical Neurophysiology, University of
6
Bournemouth, Bournemouth, UK, Neurology, Uniformed Services University of the Health Sciences,
7
Walter Reed National Military Medical Center, Bethesda, MD, USA
We will present an overview of novel, 'virtual' therapies targeting phantom limb pain (PLP). There is a
sizeable and rapidly growing population of amputees worldwide, with an estimated 700,000 amputees
in Europe and 2,000,000 in the USA. After limb amputation, 80% of patients experience PLP, which
can persist indefinitely. Additionally, numerous patients with diabetes and vascular disease report
crippling PLP.
PLP is extremely difficult to treat; multiple medication trials have failed to show efficacy.
Ramachandran developed virtual, mirror therapy, which reduced PLP in several patients, confirmed
through a randomized, clinical study by Tsao and colleagues.
After providing an overview of PLP, we will discuss our original treatments. Dr. Mercier (Canada)
assesses the relationship between phantom limb motor control and pain, and also uses pre-recorded
videos and mental visualization to treat PLP. In an immersive, virtual-reality environment, Dr. Pettifer
(UK) transposes the motions of an amputee's intact limb to a virtual, phantom limb to control a ball.
Dr. Cole (UK) uses motion capture from the residual limb to drive an avatar arm, allowing subjects to
pick up an apple or play drums. Similarly, Dr. Tsao and Ms. Perry (USA) work with a virtualenvironment platform where amputees drive an avatar limb using surface EMG signals derived from
their residual limb. This platform further serves to screen and train amputees for work with an
advanced prosthetic arm.
Collectively, our research represents a variety of techniques for treating PLP across a diverse
rehabilitation population worldwide. These treatments have substantial clinical and neuroscientific
implications.
24
BASIC AND CLINICAL EVIDENCE THAT PAINFUL LESIONS ARE INDUCED AFTER WHIPLASH
INJURY
1
2
B. Winkelstein , G. Siegmund , M. Curatolo
1
3
2
Bioengineering, University of Pennsylvania, Philadelphia, PA, USA, MEA Forensic Engineers &
3
Scientists, Vancouver, BC, Canada, University of Bern, Bern, Switzerland
Chronic pain after whiplash injury is still poorly understood and its effective treatment remains
challenging. It is widely recognized that this condition has a complex etiology, involving possible
tissue damage, central sensitization and psychosocial factors. Clinical studies suggest the facet joints
as the source of pain in 50% of patients after a whiplash. However, the almost consistent lack of
radiological signs of tissue damage often leads to the conclusion that peripheral nociception plays a
minor role in symptom development. Other tissues in the neck, like nerves and muscle, also can
undergo transient injury that may not present clinically with signs consistent with symptoms. In the
context of the biopsychosocial model, there is a need to improve our knowledge of the contributing
factors to nociception in whiplash-associated disorders. Recently, research in the fields of
biomechanics and basic science has provided data that converge towards the importance of tissue
lesions as sources of pain after whiplash injury. This session will present recent data on the
mechanisms and prevention of painful injury after whiplash. The relevant cellular and biochemical
pathways of nociception and pain will be reviewed in the context of tissue injury. The mechanisms of
injury will also be integrated within the multifactorial context of the determinants of pain and disability
after trauma. Areas of agreement and controversy on diagnosis and treatment of painful lesions will
be highlighted. The target audience is clinicians dealing with chronic pain after whiplash injury, and
basic researchers interested in the mechanisms of musculoskeletal pain.
25
ADVANCES IN THE EARLY RECOGNITION, PATHOPHYSIOLOGICAL UNDERSTANDING AND
TREATMENT OF CENTRAL POST-STROKE PAIN WITH EMPHASIS ON THALAMIC LESIONS
1
2
T. Sprenger , T.R. Toelle , H. Klit
1
3
2
Department of Neurology, University Hospital Basel, Basel, Switzerland, Department of Neurology,
3
Technische Universitaet Muenchen, Munich, Germany, Danish Pain Research Center, Aarhus
University Hospital, Aarhus, Denmark
Central post-stroke pain (CPSP) of thalamic origin is a central neuropathic pain condition typically
characterized by hemibody pain following thalamic strokes. Patients suffer from severe, often burning
chronic pain, leading to a major impairment of their quality of life. Allodynia, aftersensations and
spreading sensations are also common findings in patients with CPSP. Early findings of dysesthesia
or allodynia in stroke patients increase the risk of developing CPSP, suggesting that neuronal
hyperexcitability, which may in turn reflect central sensitization, in some cases preceeds central pain.
Unfortunately, the disorder is notoriously difficult to treat. Interestingly, the pain does often not
develop until days to weeks after the stroke, suggesting some mechanisms relating to downstream
degeneration or brain plasticity. This time window may allow for preemptive treatment approaches
after thalamic stroke if patients at high risk could be identified. This would necessitate an improved
understanding of implicated symptoms, thalamic nuclei and of the pathophysiology of the disorder.
In this workshop, we will discuss the state of the art in the management of patients with CPSP of
thalamic origin as well as pathophysiological mechanisms and advances in the identification of
patients at risk of developing thalamic pain after thalamic strokes.
26
SOCIAL JUSTICE, FAIRNESS AND PAIN
1
2
1
M. Sullivan , J. McParland , W. Scott
1
2
Psychology, McGill University, Montreal, QC, Canada, Psychology, Glasgow Caledonian University,
Glasgow, UK
Social justice appraisals refer to evaluations about fairness. These judgments are likely to be brought
to bear following the experience of an undeserved loss, such as sustaining a debilitating injury or
developing a chronic health condition. This session will provide an overview of research and theory on
the relation between justice-related appraisals and pain outcomes. Two justice-related constructs that
have received increased attention in recent years include just world beliefs, and perceived injustice.
Just world beliefs refer to the need to believe that one lives in a world where people generally get
what they deserve. Just world beliefs have been shown to influence adaptational outcomes of
individuals suffering from chronic pain. Perceived injustice has been construed as an appraisal
comprising an exaggerated sense of the magnitude and permanence of loss, coupled with external
blame attributions. Perceived injustice has been shown to be a powerful predictor of recovery
trajectories following injury. Michael Sullivan, PhD will summarize research highlighting the
prognostic value of measures of perceived injustice for adverse pain outcomes. The presentation will
address issues related to the origins of perceptions of injustice, and propose avenues for prevention
and intervention. Johanna McParland, PhD will present the results of qualitative and quantitative
studies addressing the role of just world beliefs in adaptation to chronic pain. Finally, Whitney Scott,
BA, will report findings from recent studies addressing the emotional vehicles through which
perceptions of injustice might impact on pain experience, depression and disability. Potential avenues
for intervention will be addressed.
27
CRPS: NOVEL SIGNS, NOVEL TREATMENTS
1
2
3
4
R. Baron , T.S. Jensen , L. Knudsen , J. Lewis , D.J. Jeroen R
1
5
2
3
Neurology, Universitätsklinikum Schleswig-Holstein Kiel, Kiel, Germany, Neurology, Danish Pain
4
Research Center, Aarhus University Hospital, Aarhus, Denmark, Bath Centre for Pain Services, The
5
Royal National Hospital for Rheumatic Diseases NHS Trust, Bath, UK, Department of Rehabilitation,
University Hospital Maastricht, Maastricht, The Netherlands
The Complex Regional Pain Syndrome (CRPS) occurs after limb trauma and is characterized by a
plethora of clinical symptoms: autonomic, motor, sensory, sympathetic, and inflammatory symptoms
and central reorganization. CRPS associated chronic pain and the debilitating symptoms lead to loss
of function and high socioeconomic costs since the patients need long-term treatment and are unable
to return to work.
Currently, the underlying mechanisms of CRPS and its separation from neuropathic pain is not clear,
which is reflected in the existing guidelines and classifications. Troels S. Jensen and Ralf Baron will
review similarities and differences of the two pain conditions. This will also be illustrated by the
somatosensory profiles seen in CRPS and neuropathic pain.
Lone Knudsen will based on studies of near-infrared spectroscopy during orthostatic stress discuss
the involvement of deeper structures in CRPS. CRPS patients show an abnormal reduction in cardiac
output to upright tilt that is not compensated by an increase in heart rate. The studies indicate that
there are complex somatosensory and autonomic changes in CRPS involving both superficial and
deep somatic structures.
J. Lewis will describe how visually altering the appearance of the painful limb can modulate pain and
explore the potential use of visual illusions in the treatment of CRPS.
J. de Jong will demonstrate that “use it or lose it“ is most important - despite pain and autonomic
signs. The reduction of pain-related fear through a graded exposure in vivo treatment is associated
with restoration of functional abilities.
28
USE OF ANALGESICS FOR HEADACHE: A CURSE OR A BLESSING?
1
2
3
T.J. Steiner , P. Calabresi , R.H. Jensen , Z. Katsarava
1
4,5
2
Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway, Neurology,
3
University of Perugia, Perugia, Italy, Neurology, University of Copenhagen, Copenhagen, Denmark,
4
5
Neurology, Evangelisches Krankenhaus, Unna, Neurology, University of Duisburg-Essen, Essen,
Germany
Although medication-overuse headache (MOH) is certainly common in the general populations of
developed countries, epidemiological data are limited. The worldwide prevalence may be 1-2% in
adults. The Global Burden of Disease Study 2010 provides data for estimating the disability burden
attributable to MOH, although considerable uncertainty surrounds the estimate. A major global publichealth knowledge gap needs urgently to be filled.
There are various hypotheses concerning the pathophysiology of MOH. It has been postulated a
central sensitisation from repetitive activation of nociceptive pathways mimicking a pathological brain
plasticity. Some authors have postulated alterations of the serotoninergic, dopaminergic and
cannabinoid systems. We propose an integrated view by comparing these mechanisms with those
reported for other forms of drug addiction.
A precise diagnosis maybe difficult to obtain as more than 50% of chronic headaches are complicated
by medication overuse, where an overuse of analgesics and/or triptans becomes the causative factor
for chronification. It is essential to identify a medication overuse headache as a detoxification is the
first important step in the treatment plan and successful reversion to episodic headache is achieved in
up to 72% of socalled refractory headache patients. In recent years multidisciplinary treatment is also
successfully applied in many countries and evidence is accumulating.
Medication overuse headache develops following overuse of headache drugs. Other factors such as
low socio economic status, psychological co-morbidities are important as well. Treatment includes
withdrawal, prevention of primary headache and psychological/behavioural support.
29
CHRONIC HEADACHE - A CLINICAL CHALLENGE
R. Jensen
Danish Headache Center, Department of Neurology, University of Copenhagen, Glostrup Hospital,
Glostrup, Denmark
Chronic headache affects 4-8 % of the general population in Europe and due to very high indirect
costs rank among top 5 of most costly disorders based on recent a WHO-report. Most patients with
chronic headache are severely disabled hereof and have suffered from headache for many years
before they are referred to headache specialists. Pharmacological treatments of primary headache
disorders have only been partially effective and may have had cumbersome side effects, so other
aspects of pain management are often required. A precise diagnosis maybe difficult to obtain as more
than 50% of chronic headaches are complicated by medication overuse, where an overuse of
analgesics and/or triptans becomes the causative factor for chronification. It is essential to identify a
medication overuse headache as a detoxification is the first important step in the treatment plan and
successful reversion to episodic headache is achieved in up to 72% of socalled refractory headache
patients. In recent years multidisciplinary treatment is also successfully applied in many countries and
evidence is accumulating. There is however still room for therapies with better efficacy and tolerance
and neurostimulation techniques may have this potential for carefully selected patients. The latest
research results published in the field will be summarized and discussed.
30
PREDICTING PERSISTENT POSTSURGICAL PAIN (PPSP) WITH QST
1
2
E. Pogatzki-Zahn , S. Haroutiunian , D. Fletcher
3
1
Anesthesiology, Intensive Care Medicine and Pain Therapy, University Clinic of Muenster, Muenster,
2
3
Germany, Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark, Service
d'Anesthesie Reanimation, Hospital Raymond Poincare´ AP-HP; Universite´ Versailles St Quentin,
Paris, France
Persistent Postsurgical Pain (PPSP) is a common problem that affects approximately 20% of all
operated patients. However, the etiology of PPSP is almost unknown (maybe "poorly understood"?).
During the past years, a number of factors contributing to PPSP have been indicated. The role of
nerve injury during the surgical procedure is one of these factors; patients undergoing surgical
procedures with major nerve damage are at greater risk for developing PPSP. However, some
patients do not present PPSP although a nerve injury occurred and other patients develop PPSP
although nerve injury is minimal. Thus central sensitization caused by other surgical factors (e.g.
inflammation) or by an overall susceptibility of patients may also contribute to PPSP. In the present
symposium we will discuss the role of nerve injury and the interaction of neuropathic and
inflammatory-like mechanisms for PPSP. Furthermore, we will indicate how quantitative sensory
testing (QST) can help to identify patients with risk factors early after surgery. Finally, we will address
the question, if more susceptible patients with a greater risk for developing PPSP can be detected by
preoperative QST or conditioned pain modulation (CPM). In conclusion, the symposium will help to
understand the role of neuropathic mechanisms, central sensitization and pre-existing hypersensitivity
for the development of persistent pain after surgery.
31
A HARD LOOK AT REHABILITATION FOR LOW BACK PAIN
1
2
2
3
H.G. Kress , X. Michail , E. Kouloulas , R. Casale , S. Erdine
4
1
Dept. of Special Anaesthesia and Pain Therapy, Medical University of Vienna/AKH, Vienna, Austria,
3
European Academy of Rehabilitation Medicine, Athens, Greece, Dept. of Clinical Neurophysiology,
4
Foundation 'Salvatore Maugeri' - IRCCS, Montescano, Italy, Dept. of Pain Management, Istanbul
Pain Center, Istanbul, Turkey
2
“Should I stay or should I go” is the refrain of a pop song and it reflects one of the hard-to-answer
questions often posed by patients with LBP. In other terms, should we prescribe rest or prescribe a
rehabilitation program. Then again, when and what kind of rehabilitation can/should be prescribed
(and for what kind of LBP) as a wide range of conservative treatments have been proposed without
clear differences in pain control and improvement of the quality of life. Indeed for many of these non
pharmacological treatments , there is a great and substantial overlapping between the two specialties:
pain medicine and rehabilitation. Among the most controversial issues are the entangled relationships
between movement-induced pain and movement as pain treatment, as well as the use of
neuromodulation in terms of site of application (trans- or per-cutaneous; peripheral or central) and
stimulation parameters. In this field the past decade has been an era of tremendous innovation in
SCS where high-frequency paresthetic-free stimulation as a potential treatment for chronic low back
pain has been also introduced. The aim of this workshop is to tackle the following topics:
1 - Rehabilitation for LBP - When and what? Efthimios Kouloulas
2 - Pain and motility: an entangled relationship in LBP. Roberto Casale
3 - Neuromodulation: the more central, the better? Ten years after the consensus statement by the
task force of EFIC. Serdar Erdine
Question Time: What messages pain medicine and physiatry have to take home (HG Kress & X.
Michail)
32
THALAMIC MECHANISMS INVOLVED IN MIGRAINE PATHOPHYSIOLOGY - BEYOND
CONVENTIONAL CONCEPTS
1
2
3
A.P. Andreou , R. Burstein , A. May , G. Coppola
4
1
Headache Research-Section of Anaesthetics, Pain Medicine and Intensive Care, Faculty of
2
Medicine, Imperial College London, London, UK, Department of Anesthesia and Critical Care,
3
Harvard Medical School, Boston, MA, USA, Department of Systems Neuroscience, University
4
Medical Centre Hamburg-Eppendorf, Hamburg, Germany, Department of Medico-Surgical Sciences
and Biotechnologies, Sapienza University of Rome Polo Pontino, Rome, Italy
Migraine is a painful and disabling chronic neurological condition affecting about 15% of the worlds
population, both children and adults, with a significant socioeconomic cost. The disorder is
characterised by episodic attacks of intense headache accompanied by sensory disturbances. The
lack of effective, migraine-specific treatments for all patients reflects our limited understanding of the
underlying pathomechanism of the condition. Clinical and preclinical data indicate that the thalamus is
a key brain area involved in migraine pathophysiology; however its role in the generation of many
migraine symptoms has been ignored. In brain imaging studies, thalamic activation and sensitization
are consistently seen during spontaneous and induced migraine attacks. The pharmacology of
thalamic areas that process trigeminovascular information provides interesting insights into migraine
pathophysiology, as they are a prominent site of action of triptans and of clinically active preventives.
The modulation of sensory transmission in the thalamus, assumes further significance as it has been
shown to be a pivotal area for the development of sensory hypersensitivity to visual stimuli.
Furthermore, sensitization of third order thalamic neurons has been implicated in the development of
whole-body allodynia that is frequently seen in migraine patients. The role of thalamic mechanisms in
migraine pathophysiology should be re-evaluated beyond conventional concepts.
33
HUMOR - A NEW STRATEGY FOR PAIN TREATMENT IN MULTIDISCIPLINARY PROGRAMS?
1
2
1
T. Benz , W. Ruch , C. Pello , R. Brioschi
1
1
2
Pain Center, RehaClinic, Bad Zurzach, Department of Psychology, University of Zurich, Zurich,
Switzerland
Humor can be used as a strategy for increasing pain tolerance and health-related quality of life in
persons with chronic disabling pain and for increasing work satisfaction in members of the
interdisciplinary pain management team.
Although there is no absolute consensus among scientists and clinicians on exactly what humor is,
humor may lead to a change in physical and psychological aspects of human suffering (e.g. release of
endorphins and reduction of muscle tension) and hence humor can reduce pain.
Humor may help to reflect on pain, and help both persons with chronic disabling pain and members of
the interdisciplinary pain management team to cope with the burden of pain. Humor can be used as a
cognitive technique (e.g. distraction) for pain control and increasing pain tolerance. We can state with
some confidence that the phenomenon of humor-induced pain tolerance is real. For a pain tolerance
effect to occur, individuals should enjoy themselves in an unrestrained manner, not blending
enjoyment with any other emotions, and they should not be forced to laugh. An intermediate degree of
exhilaration or enjoyment seems to be most effective.
The main objective of this topical session seminar is to discuss the scientific evidence of the thesis
“laughter as a painkiller”, to demonstrate how humor strategies can be implemented in
interdisciplinary pain programs and to present a practical demonstration of humor interventions and
so called “humor instruments” which we use in our interdisciplinary pain programme for persons with
chronic disabling pain.
34
THE C TACTILE SYSTEM: PAIN INHIBITION, PAIN SIGNALING, OR BOTH?
1
2
3
H. Krämer , J. Liljencrantz , S. Leknes , H. Olausson
1
4
2
Neurology, Justus Liebig University Giessen, Giessen, Germany, Institute of Neuroscience and
Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,
3
4
Department of Psychology, University of Oslo, Oslo, Norway, Department of Clinical
Neurophysiology, University of Gothenburg, Gothenburg, Sweden
Human hairy skin contains unmyelinated low-threshold mechanoreceptors called C tactile (CT)
afferents. Despite being C fibers, these afferents do not mediate pain under normal conditions but
seem to play a decisive role in the perception of affective and emotional aspects of touch. Single unit
microneurography recordings show that CTs are most reliably activated by slow skin stroking
(stimulation velocity: 1-10 cm/sec). Brain imaging studies suggest that CT information is processed in
a network that includes the insular, orbitofrontal and anterior cingulate cortices. CT fibres are closely
linked with reward as they preferentially fire during pleasant touch. We present recent evidence of CTmediated pain modulation in humans, as previously demonstrated in rodents. CT-induced pain relief
is centrally mediated and may draw on reward circuitry. Thus, a picture has emerged where CTs form
part of a limbic related brain network contributing to the maintenance of emotional and physical wellbeing through their capacity to signal pleasure. In pain conditions, CT afferents appear to change their
functional properties. In experimental allodynia, a contribution of the CT system is suggested in both
humans and animals. In chronic pain patients, CT afferent stimulation is not perceived as pleasant
anymore, even in the absence of allodynia. In sum: when there is pain - or allodynia - CT fibers lose
the ability to mediate pleasantness of touch.
35
CENTRAL SENSITIZATION WITH MUSCULOSKELETAL PAIN: MECHANISM-BASED
CLASSIFICATION CRITERIA AND TREATMENTS?
1
2
3
O.K. Andersen , M. Curatolo , M. Sterling , J. Nijs
4
1
Center for Sensory-Motor Interaction, Department of Health Science & Technology, Aalborg
2
3
University, Aalborg, Denmark, University of Washington, Seattle, WA, USA, University of
4
Queensland, Brisbane, QLD, Australia, Human Physiology & Physiotherapy, Vrije Universiteit
Brussel, Brussels, Belgium
Many patients with chronic musculoskeletal pain, including those with spinal pain, whiplash,
fibromyalgia, subacromial impingement syndrome, headache, osteoarthritis, and tennis elbow show
features of central sensitization, a process characterized by generalized hypersensitivity of the
somatosensory system. Several models in animals exist for spinal sensitization in the dorsal horns.
The evidence is based on persistent increased neuronal activity at the spinal level and/or facilitation of
the nociceptive withdrawal reflexes following strong conditioning input. In humans, evidence for
central sensitization is coming from several studies showing allodynia and hyperalgesia in the skin
following application of algogenic substances, electrical stimulation or mild injuries to the skin. For
deep tissue, referred pain is used as an indicator of central sensitization in human studies. However,
for most of these human experimental studies the evidence is based on psychophysical methods,
while only few studies have shown facilitation of nociceptive withdrawal reflexes, the most direct
evidence for spinal nociception in humans. On the other hand, clinical studies showing increased
reflex excitability in chronic pain patients are emerging and the nociceptive withdrawal reflex is
suggested as biomarker for pain diagnostics, treatment efficiency and for testing analgesics.
Why is it so difficult to reproduce findings of animal experiments in human models? Are nociceptive
withdrawal reflexes sufficiently sensitive and reproducible to detect subtle changes in spinal
nociceptive excitability?
Besides spinal sensitization in the dorsal horns, central sensitization encompasses altered sensory
processing in the brain, malfunctioning of descending anti-nociceptive mechanisms, increased activity
of top-down pain facilitatory pathways, long-term potentiation, and an extended and hyperactive pain
neuromatrix. However, not all chronic pain patients have central sensitization, and clinicians struggle
identifying those having central sensitization pain. Clinical classification criteria, together with a
classification algorithm, for the differential classification of CS pain, nociceptive and neuropathic pain
will be presented. Although based on a body of research findings, the classification criteria and
algorithm require experimental testing in future studies.
This workshop will review the evidence for central sensitization in chronic musculoskeletal pain
patients, highlight its prognostic value and the potential for a better characterization of the individual
pathophysiology based on the assessment of sensitization processes.
36
WHICH INTERVENTIONS CAN PREVENT TRANSITION FROM ACUTE TO CHRONIC PAIN?
1
2
1,3
A. Stubhaug , E. Aasvang , S. Reme
1
Department of Pain Management and Research, Oslo University Hospital, Rikshospitalet, Oslo,
2
3
Norway, Department of Anaesthesiology, Rikshospitalet, Copenhagen, Denmark, University of
Aalborg Bergen, Bergen, Norway
Acute pain is a warning signal of ongoing tissue injury. As the tissue heals, pain usually subsides.
In some subjects the pain persists long after normal tissue healing and may develop into a chronic
pain condition.
We know of quite a few risk factors for chronicity. These risk factors include psychosocial factors,
gender, age, BMI, nociceptive function and comorbid pain conditions. Altogether, knowledge about
these factors enable us to create an individual risk profile. When should we do such a risk profile
examination, and what are the possible interventions for prevention of chronic pain?
Psychological interventions have a proven ability to reduce the risk for chronicity. When, and how
should such interventions be introduced? This will be reviewed in light of recent research.
A special chance for prevention of chronic pain isbefore surgery. May be as many as 2-10% of
patients develop disabling pain after surgery. Possible interventions during and after surgery that can
reduce the risk for persistent pain will be reviewed.
References:
Johansen A, Romundstad L, Nielsen CS, Schirmer H, Stubhaug A. Persistent postsurgical pain in a
general population: prevalence and predictors in the Tromsø study. Pain. 2012 Jul;153(7):1390-6.
Theunissen M, Peters ML, Bruce J, Gramke HF, Marcus MA. Preoperative anxiety and
catastrophizing: a systematic review and meta-analysis of the association with chronic postsurgical
pain.Clin J Pain. 2012;28(9):819-41.
Reme SE, Hagen EM, Eriksen HR. Expectations, perceptions, and physiotherapy predict prolonged
sick leave in subacute low back pain. BMC Musculoskelet Disord. 2009 ;10:139. 1471-1474.
37
PERCEPTION OF PAIN, BODY, AND MIND: FROM FUNDAMENTAL RESEARCH TO NOVEL
TARGETS FOR TREATMENT
1
2
3
A. Meulders , T.R. Stanton , J. Trojan , C.F. Berryman
1
2
2
Psychology, KU Leuven, Leuven, Belgium, Body in Mind Research Group, The Sansom Institute for
3
Health Research, University of South Australia, Adelaide, SA, Australia, Department of Psychology,
University of Koblenz-Landau, Landau, Germany
What we perceive is often not an accurate depiction of reality. This appears particularly true in people
suffering from chronic pain. Experimental and clinical evidence indeed suggests that various factors
influence the perception of pain and how we experience it, such as emotions (i.e. pain-related fear),
cognitions and increased attention towards pain, but also multisensory integration and body schema.
Given that these factors modulate the maintenance of chronic pain, focused fundamental research
might contribute to the optimization of existing treatments, point to novel treatment targets and
promote cost-effective health care.
This symposium will provide the latest academic efforts in this area. Dr. Ann Meulders will present
experimental evidence showing that mere intention to perform a painful movement can come to elicit
conditioned fear of movement. These results demonstrate that associative learning processes in fear
of movement reach beyond actual movement. Dr. Tasha Stanton will focus on changes in body
perception and body schema in chronic pain and multisensory illusions as a way to target these
dysfunctions in a therapeutic framework. Dr. Jörg Trojan will examine the differences in perceptual
maps of the hand in Complex Regional Pain Syndrome relative to healthy controls. Carolyn Berryman
will provide a detailed review on working memory deficits in chronic pain, and discuss the possibility to
improve/train working memory as a treatment approach. Finally, the chair and co-chair will discuss
potential implications for clinical practice and suggest avenues for further scientific enquiry.
38
ACUTE PAIN IN EUROPE
1
1
2
W. Meissner , R. Zaslansky , M. Puig , E. Pogatzki-Zahn
3
1
Dep. of Anesthesiology and Intensive Care, Friedrich Schiller University Jena, Jena, Germany,
Department of Anaesthesiology, Hospital del Mar-Universitat Autonoma Barcelona, Barcelona,
3
Spain, Dep. of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster,
Muenster, Germany
2
Inadequate management of pain after surgery leads to poor recovery, reduced quality of life, fosters
development of disabling chronic pain, and increases health care costs. Surveys, worldwide, show
that despite availability of high-quality guidelines and advanced pain management techniques, the
quality of postoperative pain management is far from satisfactory, and variation of care is tremendous.
One reason for this discrepancy is that healthcare providers lack suitable measures for evaluating the
quality of care they provide. When quality is assessed, the focus is generally on structures and
processes. These are surrogate measures. Patient reported outcomes (PROs) are not often
employed. PROs capture the effect of the services provided on the patient´s health and well being.
PAIN OUT is the world´s largest registry project on acute pain, it was founded and developed with
funds from the European Commission's FP7. It comprises feed-back and benchmarking of PROs, a
knowledge information system and case-based clinical decision support. PAIN OUT is now open for
participation of hospitals worldwide.
This seminar will describe the project and present first results. It will demonstrate the role PAIN OUT
had in assisting hospitals to improve the quality of pain management. Additionally, it will show how to
identify patients at risk of experiencing severe postoperative pain.
At the end of the seminar, attendees will have become acquainted with PAIN OUT, the options it
offers for assessing quality of perioperative pain management and requirements for joining the
project.
39
MECHANISMS AND MODELS OF HYPERALGESIC PRIMING: FROM HINDPAW TO HEADACHE
TO HUMANS
1
1
2
T. Price , G. Dussor , W. Magerl
1
2
University of Arizona, Tucson, AZ, USA, University of Heidelberg, Heidelberg, Germany
Hyperalgesic priming has emerged as an important model system to study mechanisms of chronic
pain. This session will address recent advances in this area ranging from preclinical work in rodents to
potential applications in humans. Ted Price will discuss novel mechanisms involved in CNS-mediated
maintenance of hyperalgesic priming. These mechanisms include activation and translation of atypical
PKCs, BDNF/trkB signaling and synaptic adhesion molecules. Greg Dussor will discuss how
hyperalgesic priming models can be adapted to study headache chronification. He will show how
priming gives insight into CNS-mediated mechanisms of headache related plasticity. Finally, Walter
Magerl will describe studies of pain plasticity in humans using a variety of surrogate models and
discuss how these might be relevant to understanding how mechanisms involved in priming can help
us understand chronic pain in humans. Hence, the symposium will offer unique insight into how
mechanisms of pain plasticity contribute to the development of chronic pain.
40
SCRATCHING THE SURFACE - WHAT ABOUT DEEP TISSUE NOCICEPTION?
1
2
S. Sikandar , R. Baron , A.H. Dickenson
1
1
2
Neuroscience, Physiology & Pharmacology, University College London, London, UK, Department of
Neurology, Universitatsklinikum Schleswig-Holstein, University of Kiel, Kiel, Germany
The paucity in knowledge of deep tissue nociceptive signaling compared to cutaneous pain leads to
challenges in treating debilitating chronic pain syndromes such as fibromyalgia, back pain,
postherniotomy and other postsurgical pains. Indeed, neuropathies can also affect deep tissue
innervation. Nevertheless, in most instances, both preclinical and clinical studies focus on superficial
somatic sensory processing by using cutaneous stimulation to measure evoked behavioural/neuronal
responses or sensory measures. Despite phenotypic similarities between muscular and cutaneous
pain syndromes, such as patients with fibromyalgia or neuropathy, nociceptive processing from deep
tissues is poorly explored.
Here we outline sensory processing of deep somatic tissue compared to superficial cutaneous
signaling in terms of spinal and supraspinal pathways. We discuss what we know through preclinical
models about changes in the activity and excitability of central neurones in chronic muscle pain
syndromes, including the descending influences from the brainstem that mediate muscle nociception.
We then discuss how the overlap of sensory profiling of patients with superficial somatic pain with
patients with deep tissue pain can be used to explore common disease mechanisms and treatment.
Finally we relate the pathways involved in deep tissue nociception back to drug mechanisms of
analgesic treatments given to patients with muscular disorders like fibromyalgia and back pain.
41
GENETIC SUSCEPTIBILITY TO CHRONIC PAIN AND CO-MORBID DEPRESSION: ELUCIDATING
PLEIOTROPIC EFFECTS?
1
2
3
4
M.I. Hasenbring , J. McBeth , N. Pedersen , K. Holliday , M. Lebe
1
5
2
Dept. of Medical Psychology and Sociology, Ruhr-University Bochum, Bochum, Germany, Arthritis
Research UK Epidemiology Unit, School of Translational Medicine, University of Manchester,
3
Manchester, UK, Dept. of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm,
4
5
Sweden, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK, Dept. of
Medical Psychology and Sociology, Ruhr-University of Bochum, Faculty of Medicine, Bochum,
Germany
There is increasing evidence that suffering from pain at multiple sites and co-morbid depression
characterize chronic stages of a pain disorder, which may develop from regional pain (e.g. low back
pain) over months and years. Both, pain and depression are known to be influenced by psychological
distress on the one hand, twin studies have shown a heritable effect on the other. However, recent
research suggests potential pleiotropic effects, although the interrelation between genetic effects on
pain, distress and depression are largely unknown. Candidate gene association studies revealed
preliminary evidence on the role of genes that modulate neuroendocrine pathways, such as the
serotonergic (5HT) system that may be involved in the relationship between pain, distress and
depression. Research has mainly focused on the HTR2A gene, which encodes for the serotonin
receptor 2A gene and the promoter variant (5HTTLPR). Only a few studies focused on the role of the
5HTR1A receptor gene. The present workshop presents and discusses recent findings on twin
studies in chronic functional pain disorders (Nancy Pedersen), results of candidate gene association
research in chronic widespread pain disorders (Kate L. Holliday) and a potential pain x gene x gender
interaction in the presence of depression in patients suffering from local pain after disc surgery (Moritz
Lebe).
42
THE SPATIAL RESOLUTION OF THE NOCICEPTIVE SYSTEM
1,2
1,3
2
2
3
A. Bauleo , F. Mancini , F. Lui , C.A. Porro , P. Haggard , G.D. Iannetti
1
1
Department of Neuroscience, Physiology and Pharmacology, University College London, London,
2
UK, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio
3
Emilia, Modena, Italy, Institute of Cognitive Neuroscience, University College London, London, UK
Background and aims: A systematic study of the spatial resolution of the nociceptive system across
different body districts is surprisingly lacking, especially considering the recent description of a fovea
for pain at the fingertips (Mancini et al Curr Biol 2013). In this psychophysical study we assessed the
spatial acuity of ten body regions, using the two-point discrimination (2PD) of Nd:YAP laser pulses
that selectively activate Aδ cutaneous afferents.
Methods: Using two Nd:YAP lasers we delivered either one or two simultaneous pulses (diameter:
1.3 mm) of identical energy on each of the following body sites: forehead, volar forearm, hand
dorsum, hand palm, fingertip, shoulder, lower back, upper thigh, calf, and foot dorsum. The 2PD task
consisted in judging whether one or two stimuli were delivered, using ascending and descending
staircases of varying spatial distance between the two pulses. Single stimuli were included as catch
trials. All stimuli elicited a clear pinprick sensation related to the activation of Aδ afferents.
Results: We found a proximal-distal gradient of spatial acuity for nociceptive stimuli, with higher
acuity for proximal stimuli, an observation in agreement with innervation density of skin nociceptors
and perceptual threshold of Aδ stimuli. Two distal regions (fingertips and palm) represented an
exception, and showed maximal spatial acuity (see also Mancini et al., 2013).
Conclusions: This study provides the first systematic description of spatial acuity of the nociceptive
system across the entire body in healthy participants.
43
STIMULATING AΔ AND C-FIBERS IN THE LOWER LIMB WITH A 980 NM DIODE LASER
1
1
2
3
I. Krabbenbos , E. van Dongen , S. Tromp , C. van Swol , E. Boezeman
1
2
2
3
Anesthesiology, Clinical Neurophysiology, Medical Physics, St Antonius Hospital, Nieuwegein, The
Netherlands
Background and aims: This study attempts to stimulate Aδ and C fibers separately with a 'grid' to
generate respectively late and ultra-late LEPs.
Methods: A 'grid' is a thin aluminum plate used as a spatial filter to stimulate C-fibers. Furthermore,
study subjects pressed a button upon detecting a laser stimulus which was used to measure reaction
times (RT) following diode laser stimulation. Cutaneous heat stimuli were applied at the Th 12 and L5
dermatoma in seventeen volunteers. Conduction velocities (CV) were calculated by measuring
latencies of P2 and reaction times (RT).
no-grid
no-grid
Results: Stimulation condition Th12
showed a P2late response at 330 ± 47 ms and L5
at 413 ±
no-grid
no-grid
grid
53 ms. Mean reaction time during Th12
was 537 ± 146 ms, L5
784 ± 334 ms, Th12 710 ±
grid
grid
grid
195 ms and L5 1391 ± 336 ms. During stimulation block Th12 and L5 ultra-late LEPS could not
reliably be generated. Median conduction velocities (CV) and their corresponding range were
calculated. The median CVRT no grid was 5.8 m/s (range 1.2-43.3). The median CVLEP no grid was
13.8 m/s (range 4.7-45.4). The median CVRT grid was 1.9 m/s (range 0.8-3.7). Ultra-late LEPs could
grid
grid
not be generated, although subjects mentioned a long lasting burning pain during Th 12 and L5 .
Conclusions: This study questions the feasibility of the 'grid' to reliably generate C-fiber responses.
Pressing a button upon laser stimulus detection seems preferable for identifying C-fiber stimulation in
the lower limb, whereas for Aδ nociceptive pathways laser evoked potentials might be of use.
44
MULTIPLE IMPAIRMENTS OF CUTANEOUS NOCICEPTOR FUNCTION BY ADRIAMYCIN
1
2
1
1
1
K. Boros , M. Katona , O. Oszlács , M. Dux , P. Sántha , G. Jancsó
1
1
2
Department of Physiology, Department of Pediatrics, University of Szeged, Szeged, Hungary
Background and aims: Anthracycline-type cytostatic agents exert significant neurotoxic actions on
primary sensory neurons. This study examined the effects of cardiotoxic doses of adriamycin on the
function and morphology of cutaneous nociceptive nerves which express the transient receptor
potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin type 1 (TRPA1) receptors.
Methods: Adult male Wistar rats were given adriamycin (cumulative dose: 15 mg/kg) or its vehicle.
Capsaicin- and allyl-isothiocyanate-evoked cutaneous neurogenic sensory vascular reactions, thermal
and mechanical sensory thresholds were measured with laser Doppler flowmetry, Evans blue leakage
technique, Hargreaves' method and plantar aesthesiometry, respectively. Inflammatory hyperalgesia
was evaluated in the carrageenan model. Cutaneous innervation was assessed with
immunohistochemistry. Capsaicin-evoked release of CGRP from peripheral nerves was measured
with ELISA.
Results: Adriamycin treatment resulted in dramatic reductions in cutaneous neurogenic sensory
vasodilatation, plasma extravasation and neural CGRP release. Nociceptive heat withdrawal latencies
were significantly increased whereas carrageenan-induced inflammatory hyperalgesia was abolished
following adriamycin treatment. Immunohistochemistry revealed a substantial loss of epidermal
TRPV1-immunoreactive nerves.
Conclusions: Adriamycin induced reductions in capsaicin- and allyl-isothiocyanate-evoked
cutaneous vascular reactions, inflammatory hyperalgesia and peptide release indicate impairments in
the function of chemosensitive afferents which express the TRPV1 and TRPA1 receptors.
Histochemical and biochemical findings suggest that loss of sensory nerves significantly contributes to
the mechanisms of these changes. Since cardiac chemosensitive afferent nerves exert
cardioprotective effects, monitoring of chemosensitive cutaneous afferent nerve function may well
have predictive value to detect early deterioration of cardiac function in the course of adriamycin
therapy.
Supported: OTKA-K-101873, TAMOP-4.2.2.A-11/1/KONV-2012-0052.
45
ENDOGENOUS VANILLOIDS ARE POTENTIAL ACTIVATORS OF THE TRIGEMINAL
NOCISENSOR COMPLEX: RELEVANCE TO HEADACHE MECHANISMS
M. Dux, N. Tassi, É. Deák, G. Jancsó
Department of Physiology, University of Szeged, Szeged, Hungary
Background and aims: Our recent observations indicate that a significant population of dural
trigeminovascular afferent nerves coexpress the archetypical nociceptive channel transient receptor
potential vanilloid type 1 (TRPV1) receptor and calcitonin gene-related peptide (CGRP). The
activation of TRPV1 receptors by exogenous vanilloids, such as capsaicin, results in vasodilatation
and release of CGRP, hallmarks of neurogenic inflammation involved in the pathomechanism of
migraine. To reveal the possible activation of meningeal TRPV1 receptors by endogenous vanilloids,
the effects of anandamide and N-arachidonoyl-dopamine (NADA) were studied on dural vascular
reactions and CGRP release.
Methods: Changes in meningeal blood flow were measured with laser Doppler flowmetry in a rat
open cranial window preparation following local dural applications of anandamide and NADA, in
control and capsaicin-desensitized rats. The release of CGRP evoked by endogenous vanilloids was
measured by ELISA in an ex vivo dura mater preparation.
Results: Topical applications of anandamide and NADA induced modest and significant increases in
meningeal blood flow, respectively. NADA-induced increases in blood flow were markedly inhibited by
pretreatments with the TRPV1 antagonist capsazepine, the CGRP antagonist CGRP8-37, or by prior
systemic capsaicin desensitization. In the ex vivo dura mater preparation NADA evoked a significant
increase in CGRP release. Administration of AM251, a CB1 receptor antagonist significantly
increased the vasodilatatory effect of anandamide.
Conclusions: The present findings demonstrate that endogenous vanilloids are potential activators of
meningeal TRPV1 receptors and, consequently the trigeminal nocisensor complex. The results also
suggest that prejunctional CB1 receptors may modulate meningeal vascular responses.
Supported: OTKA-K-101873, TAMOP-4.2.2.A-11/1/KONV-2012-0052.
46
SPATIO-TEMPORAL GRADIENT OF PAIN EVOKED RESPONSES IN THE HUMAN INSULA
1,2
M. Frot , I. Faillenot
1
1,3,4
, F. Mauguière
1,2,5
2
Central Integration of Pain Unit, INSERM U-1028, Bron, Claude Bernard University Lyon 1, Lyon,
4
5
Jean Monnet University, Neurology Department, University Hospital, Saint-Étienne, Functional
Neurology and Epilepsy Department, Neurological Hospital, Bron, France
3
The insular cortex is considered as a major actor of the so-called “Pain-Matrix”. Imaging studies have
shown that pain is the stimulus that activates the largest area in this cortex, extended to all of the
insular gyri. However, little is known about the timing of activations across these insular sub-regions.
In this study, we report on the distribution of nociceptive Laser evoked potentials (LEPs) in the insula
recorded by means of depth intra-cerebral electrodes implanted in 44 epileptic patients and exploring
the whole extent of the insular cortex (82 contacts).
Our study shows that the amplitude and latency of insular LEPs vary according to the site of
recording. Both posterior and anterior insular regions respond to a peripheral pain stimulus within a
200-400ms latency range but this pain response occurs firstly, and is larger, in the posterior insula. By
recording LEPs phase reversals in both posterior and anterior insulae, our data suggest that this
spatio-temporal gradient of pain responses reflects activation of distinct sources in the caudal and
rostral parts of the insula.
By showing that pain inputs are first coded in the posterior part of the insular cortex, where they are
coded in terms of intensity and anatomical location and then conveyed in the anterior insula, where
the emotional reaction to pain is elaborated, our findings support the concept that the insular cortex is
a “key node” in pain perception and emotional reaction to pain.
47
EFFECTS OF CURRENT DENSITY ON NOCICEPTOR ACTIVATION UPON ELECTRICAL
STIMULATION IN HUMANS
1
1
1
1
1
2
G. Landmann , C. Lustenberger , L. Stockinger , A. Ljutow , M. Béchir , M. Schmelz , R. Rukwied
1
2
2
Centre for Pain Medicine, Swiss Paraplegic Centre, Nottwil, Switzerland, Department of
Anaesthesiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Background: Mechano-insensitive nociceptors have been suggested to contribute to primary
hyperalgesia and central sensitization. Also, their activation causes the development of an axon-reflex
erythema, which has extensively been monitored by Laser-Doppler-Imaging (LDI) as objective
correlate for nociceptor functionality. We compared electrical stimulation at two current densities for
nociceptor activation and thereby explored their sensitivity and applicability.
Methods: Fourteen healthy subjects (8 male, 6 female) were enrolled. Electrical stimuli were
administered to the ventral forearm and the dorsum of the foot by a pair of self-adhesive 3x10 mm
electrodes (distance 3 mm) and a pair of blunted 0.4 mm diameter platinum/iridium pin-electrodes
(distance 3 mm). Perception and pain thresholds were determined at 2 Hz stimulation frequency
(duration 0.5 ms, increase 0.1 mA per sec) and nociceptor activation was performed at 1.5-fold pain
thresholds. 10 current pulses were delivered at frequencies from 5 - 100 Hz and axon-reflex erythema
(LDI) as well as pain perception (numeric rating scale) recorded.
Results: Increasing the stimulation frequency dose dependently increased the pain perception. At the
dorsum of the foot, pain thresholds, electrically induced pain and axon-reflex erythema was
significantly higher upon stimulation with pin-electrodes as compared to adhesive electrodes. At the
ventral forearm, no difference of pain ratings was identified between the stimulation methods, but
enhanced erythema responses recorded at the pin-electrode sites.
Conclusions: Current stimuli administered at high current density with pin-electrodes is a more
sensitive and more readily tolerated method for investigating “silent” nociceptors and therefore may be
applied in neuropathic pain conditions.
48
CONTACT COOL (CEP) - AND HEAT-EVOKED (HEP) POTENTIALS IN HEALTHY SUBJECTS
AND IN PATIENTS WITH COLD ALLODYNIA
1
2
2
1
C.S. Madsen , B. Johnsen , A. Fuglsang-Frederiksen , T.S. Jensen , N.B. Finnerup
1
1
2
Danish Pain Research Center, Department of Clinical Neurophysiology, Aarhus University Hospital,
Aarhus, Denmark
Background and aims: Cold allodynia can be prominent in acute oxaliplatin polyneuropathy and may
be a feature of some neuropathic pain conditions including peripheral and central neuropathic pain.
No objective test for thermoreceptive cooling pathways has been validated. The aim of this study was
to study contact cool (CEP) - and heat-evoked (HEP) potentials in patients displaying cold allodynia
and in healthy subjects.
Methods: In patients with cold allodynia due to oxaliplain-induced painful polyneuropathy and central
pain and healthy subjects, contact-heat -and contact cool-evoked potentials are recorded. The stimuli
are delivered using a contact heat-evoked potential stimulator (CHEPS, Medoc). From a baseline
temperature of 35 °C, a thermal sensation is elicited by lowering the temperature by 3 °C and by
heating to 51 °C.
Results: The preliminary results show that following contact-cool stimuli, a biphasic response can be
identified from the vertex position (N2: 230 ms; P2: 480 ms; N2-P2 amplitude 16.4±4.0 µV) in healthy
subjects with stimuli applied to the volar forearm. In a patient with thermal sensory deficits, CEP and
HEP could be identified from stimulation in the normal area but were absent in the affected area. The
results suggest that latencies are shorter with cooling than heating and that CEP and HEP responses
are in the Aδ-fiber range.
Conclusions: Preliminary results suggest that heat- and cool-evoked potential can be reliable
recorded from the vertex following activation of distinct Aδ-fiber subpopulations in healthy subjects
and pain patients. Further results will be presented at the poster session.
49
DIFFERENT EFFECTS OF EXTRACELLULAR MGSO4 AND CALCIUM ON NERVE EXCITABILITY
S. Hager, D.R. Spahn, K. Maurer
University Hospital Zurich, Institute of Anesthesiology, Zurich, Switzerland
Background and aims: An important limitation of clinical nerve excitability studies is the difficulty of
interpreting pathological changes in excitability properties and attribute changes to defined cellular or
extracellular abnormalities. The current study aimed at investigating the impact of extracellular MgSO 4
and Calcium on nerve excitability parameters.
Methods: We used a computerized threshold-tracking program (QTRAC, ©Institute of Neurology,
London, UK) in a skin-nerve in-vitro preparation of the rat saphenous nerve. QTRAC adjusts the
stimulus intensity of a constant current stimulation to a 40% target response of the maximal Aβ action
potential and tracked the stimulus current required to elicit this target amplitude applying different
concentrations of MgSO4 and Calcium.
Results: Low concentrations of MgSO4 and Calcium led to increased excitability whereas higher
concentration had fewer effects. Both, low and high concentrations resulted in longer strengthduration time constants (τSD). After a train of preconditioning stimuli, threshold increased with low
calcium but decreased with low MgSO4. Relative refractoriness was longer with low concentrations of
calcium whereas the different concentrations of MgSO 4 did not change the relative refractory period.
After a long hyperpolarising conditioning current low concentrated calcium but not MgSO4 significantly
inhibits inwardly rectifying currents (Ih).
Conclusion: The results presented in this study have shown that application of extracellular divalent
ions MgSO4 and calcium have different effects on sensory A compound action potentials; Persistant
sodium channels, slow potassium channels and inwardly rectifying channel (Ih) are all modulated by
MgSO4 and calcium.
50
+
TEMPERATURE-DEPENDENCE OF TETRODOTOXIN-SENSITIVE AND -RESISTANT NA
CURRENTS IN IB4+VE NEURONS FROM MOUSE DORSAL ROOT GANGLIA
1
1,2
M. Mis , A. Randall , E. Stevens
1
3
2
School of Physiology and Pharmacology, University of Bristol, Bristol, University of Exeter Medical
3
School, Exeter, Pfizer Neusentis, Cambridge, UK
Background and aims: Sodium channels play a key role in the function of nociceptive afferent
neurons, whose cell bodies are located in the dorsal root ganglia (DRGs). The aim of this project is to
understand how the tetrodotoxin-sensitive (TTX-S) and the tetrodotoxin-resistant (TTX-R) sodium
current (INa+) contribute to the excitability of IB4+ve neurons at physiological temperature.
Methods: DRGs from male 4-5-week-old C57/Bl6 mice were enzymatically dissociated and cultured
for up to 48 hours. Biophysical properties of neurons labelled with fluorescently tagged IB4 lectin were
studied using whole-cell patch-clamp electrophysiology at room temperature (RT) and 35°C. The
project is funded by the Biotechnology and Biological Sciences Research Council and Pfizer.
Results: In voltage-clamp experiments the TTX-S INa+ constituted only 27% of the total INa+ at RT. The
current-voltage (I-V) relationship of the total INa+ revealed a statistically significant shift of the
activation curve in the hyperpolarised direction at 35°C, and the current decayed 4-fold faster. The
TTX-R I-V relationship was unaffected by the temperature and recovery from inactivation curves
appeared less voltage-dependent at 35°C than at RT. In current-clamp, increasing temperature to
35°C caused a ~7mV hyperpolarising shift in the resting membrane potential and a statistically
significant drop in input resistance (Ri).
Conclusion: At physiological temperatures TTX-S current appears to be the main contributor to
biophysical properties of the INa+ in mouse IB4+ neurons. Current-clamp data show that increasing
temperature causes hyperpolarisation and a decrease in Ri, probably caused by enhancing the
activity of the potassium channels expressed in DRGs.
51
MAXIMUM FOLLOWING FREQUENCY SEPARATES CLASSES OF C-NOCICEPTORS IN THE PIG
1
1
1
2
3
1
1
O. Obreja , F. Werland , M. Hirth , B. Turnquist , M. Ringkamp , R. Rukwied , M. Schmelz
1
2
Anesthesiology, University Heidelberg, Mannheim, Germany, Mathematics and Computer Science,
3
Bethel University, Arden Hills, MN, Neurosurgery, Johns Hopkins University, Baltimore, MD, USA
Background and aims: Electrical high-frequency stimulation of skin nociceptors evokes hyperalgesia
in humans. It is not clear to what extent unmyelinated nociceptors conduct high-frequency stimulation.
Using extracellular single-fiber recordings from the saphenous nerves in pig in-vivo, we investigated
peak following frequencies in different classes of unmyelinated nociceptors excited by trains of
electrical pulses.
Method: C-nociceptors were classified based on modality and activity-dependent slowing (ADS) of
conduction velocity, as polymodal, mechano-insensitive or cold nociceptors. Three trains of 24
electrical pulses (0.5 ms duration; two-times electrical threshold) were delivered at 10 s intervals, at
frequencies of 5, 10, 20, 50,100, 200 Hz in the receptive field of characterized C-nociceptors.
Results: At 5 Hz stimulation, 50% of 10 mechano-insensitive nociceptors failed to conduct all pulses,
whereas no propagation failure was observed in 11 polymodal or in 3 cold nociceptors. None out of 9
mechano-insensitive nociceptors, but 50% of 16 polymodal and 67% of 3 cold nociceptors conducted
all 72 pulses given at 100 Hz. ADS after 24 pulses at 100 Hz differentiated between polymodal and
cold nociceptors (10±0.9% vs.17.6±1%). Peak following frequencies correlated negatively to the ADS
after stimulation at 2 Hz for 3 min. The differentiation of C-nociceptor classes based solely on peak
frequencies identified correctly 68.75% of them.
Conclusion: High following frequencies were found in polymodal and cold nociceptors. Peak
conduction frequencies were intimately linked to the modality of a nociceptor class. Modulation of
peak conduction frequencies might lead to sensitized supra-threshold encoding of nociceptors.
Supported by: BMBF and DFG.
52
CHEMICAL SENSITIVITY OF RAT PRIMARY SENSORY NEURONS IS REGULATED BY
GLUCOSYLCERAMIDE SYNTHASE
P. Sántha, I. Dobos, O. Oszlács, G. Jancsó
Department of Physiology, University of Szeged, Szeged, Hungary
Background and aims: Recently, we have demonstrated that inhibition of glucosylceramide
synthase (GCS), the key enzyme of neuronal ganglioside synthesis, markedly reduced both the
activation and expression of transient receptor potential vanilloid type 1 (TRPV1) receptor of cultured
dorsal root ganglion (DRG) neurons. The present study was aimed to examine the potential role of
GCS in the activation of the TRPV1 and transient receptor potential ankyrin type 1 (TRPA1) receptors
by endogenous vanilloid/cannabinoid compounds.
Methods: Cultures of adult rat DRG were prepared and treated for 4 days with D-threo-1-phenyl-2decanoylamino-3-morpholino-1-propanol (D-PDMP, 30 µM) to block GCS. In control and D-PDMPtreated cultures, activation of TRPV1 and TRPA1 receptors by capsaicin, mustard oil, and
endovanilloids, such as N-oleoyl-dopamine, N-arachidonoyl-dopamine and anandamide was
examined using quantitative cobalt uptake assay.
Results: Administration of D-PDMP resulted in significant reductions of the proportions of cobalt
accumulating neurons following receptor activation with capsaicin (1µM 44.45±1.66% vs.
12.17±0.89%) and mustard oil (100 µM, 37.41±2.47% vs. 22.08±2.43% (p< 0.05). In control cultures
equimolar concentrations (100 µM) of endovanilloids evoked cobalt uptake in 26-32% of neurons.
Pretreatment with D-PDMP significantly reduced the effects of endovanilloids.
Conclusions: The findings disclosed a novel regulatory mechanism of the activation and expression
of nociceptive TRP ion channels in DRG neurons, which involves GCS. The results indicate a
significant modulation of nociceptor function by gangliosides, in particular GM1, through mechanisms
which may involve impairments in neuronal signalling of neurotrophins and/or the organization of
membrane lipid raft microdomains.
Supported by: OTKA-K101873, TAMOP-4.2.2.A-11/1/KONV, TAMOP-4.2.2./B-10/1-2010-001220120052, Bolyai János Scholarship.
53
NEUROCHEMICAL PHENOTYPES OF CHEMOSENSITIVE VAGAL AFFERENT NEURONS
WHICH EXPRESS THE INSULIN RECEPTOR AND INNERVATE THE RAT PANCREAS
P. Sántha, B.A. Lázár, G. Kiss, É. Hegyeshalmi, G. Jancsó
Department of Physiology, University of Szeged, Szeged, Hungary
Background and aims: Chemosensitive vagal afferents may significantly contribute to the
pathogenesis of inflammatory processes affecting both the exocrine and endocrine pancreas. Recent
observations indicated functional interactions between the insulin receptor (InsR) and the transient
receptor potential vanilloid type 1 (TRPV1) receptor co-expressed in a subset of spinal somatic and
visceral primary sensory neurons. The aim of this study was to reveal the neurochemical phenotypes
of InsR-expressing vagal primary afferent neurons which innervate the rat pancreas.
Methods: Adult male Wistar rats were given pancreatic injections of biotin-conjugated wheat germ
agglutinin (bWGA). Three days later representative serial sections were cut from the dissected
nodose ganglia. Immunohistochemistry and quantitative morphometry were used to analyse the
expression of TRPV1, InsR, substance P (SP) and calcitonin gene-related peptide (CGRP) in bWGAlabelled pancreatic afferent neurons.
Results: Quantitative analysis of retrogradely labelled neurons revealed that 18.6% of nodose
ganglion neurons projected to the pancreas. The cross-sectional areas of labelled neurons amounted
2
to 513.2±154.8 µm . Of the labelled neurons 64% showed TRPV1-, 49% InsR-, 31% SP-, and 22%
CGRP-immunoreactivity. Colocalizations of TRPV1 and InsR, SP and InsR, and CGRP and InsR
immunoreactivities were demonstrated in 35%, 17% and 8% of the labelled neurons, respectively.
Conclusions: These findings provide evidence for the colocalizations of InsR, TRPV1 and sensory
neuropeptides in pancreatic vagal afferent neurons. We suggest that insulin may modulate TRPV1
activation and subsequent peptide release from vagal afferents and contribute to inflammatory and
nociceptive mechanisms in the pancreas.
Supported by: OTKA-K101873, TAMOP-4.2.2.A-11/1/KONV, TAMOP-4.2.2./B-10/1-2010-001220120052, Bolyai János Scholarship.
54
CHRONIC GASTRIC ULCER INDUCES VAGAL AFFERENTS HYPERSENSITIVITY AND
INCREASES SOMATIC SENSITIVITY IN RATS
1
2
3
D. Zurowski , J. Wordliczek , J. Dobrogowski , P. Thor
1
2
1
3
Department of Pathophysiology, Department of Pain Treatment and Palliative Care, Department of
Pain Research and Treatment, Jagiellonian University Medical College, Cracow, Poland
Background and aims: In the present study we investigated whether visceral pain may trigger the
changes in somatic nociception and gastric vagal afferent input may contribute to the altered somatic
sensations associated with gastrointestinal disorders. Accordingly somatic pain sensitivity and vagal
afferent activity ware estimated in chronic GU and during GU healing.
Methods: We used the acetic acid-iduced gastric ulcer (GU) as a model of visceral pain. The study
was carried out on rats divided into four group with experimental chronic GU and two groups of sham
operated rats. Mechanical hypersensitivity using von Frey test was investigated on 3rd, 7th and 14th
day after GU induction and compared to sham rats. In three groups, the nodose ganglia were
removed respectively on 3rd, 7th , 14th day after gastric ulcer inducement and neuronal activation
marker (c-Fos) in vagal primary afferent neurons was assesed and compared to control group.
Results: Chronic gastric ulcers increased somatic pain sensitivity. Experimental GU healed
spontaneously within 2 weeks. Natural healing of gastric ulcers was accompanied by decreased
mechanical sensitivity. Immunohistochemical studies showed significantly increased number of Fospositive neurons in vagal nodose ganglia and it confirmed higher activity of vagal primary afferent
neurons in experimental chronic GU and during GU healing.
Conclusions: Obtained results suggest that gastric ulcer increased vagal afferents activity contribute
in visceral nociception and visceral pain triggers somatic hypersensitivity which last longer than ulcer
healing.
55
SPİNAL CORD STIMULATION AT INTRACTABLE ANGINAL PAIN
1
1
1
2
2
M. Akbas , A. Yegin , S. Sanli , R.E. Altekin , H. Yilmaz
1
2
Anesthesiology, Division of Algology, Cardiology, Akdeniz University Faculty of Medicine, Antalya,
Turkey
Introduction: Angina pectoris is severe chest pain that is often accompanied by a heavy oppressive
feeling. SCS is considered a reasonable treatment option for patients with chronic angina not
responsive to more conservative therapies and who are not able to performed coronary
revascularization surgery.
Case report: A 70-year-old female presented with anginal pain at rest despite previous surgical
revascularization, cardiac stenting. Angiography showed no lesions amenable to repeat surgery or
cardiac stenting. The patient was treated with maximum medical therapies, but she was unable to
walk more than 20 meters. She also wokes up with chest pain during sleep.
Technique of the procedure: The intervention takes place under strictly sterile conditions and
antibiotic prophylaxis.The patient is placed in a prone position on an operating table suitable for X-ray
screening. The T12-L1 vertebral level is identified by means of a C-arm. A Tuohy needle is inserted
under X-ray guidance to find the epidural space, and a eight-contact paddle electrode is placed with
its cephalad tip at the T1-T4 level left of midline. Subsequently, test stimulations are performed; the
test stimulations should overlap the areas that are painful during angina attacks. When the correct
level has been found, the lead is fixated, and the pacemaker is inserted in the right buttock.
Conclusion: In the following 3 months, the patient was able to reduce his nitrate consumption by
80%. SCS could be considered as a valid treatment alternative after all medical and invasive
managements have failed.
56
TWO YEARS EXPERIENCES OF EPIDUCER
PSYCHOSOCIAL CONSIDERATIONS
1
2
TM
ITALIAN REGISTRY: TECHNICAL AND
3
4
5
6
G. De Carolis , G. Colini Baldeschi , B. Giovanni , L. Pasquariello , M. Lucia , P. Manchiaro , F.
7
8
Intelligente , G. Ciliberto , Epiducer Italian Registry
1
2
Dept of Oncology, Pain Therapy Unit, Santa Chiara University Hospital, Pisa, Ospedale S. Giovanni
3
4
dell'Addolorata, Roma, Azienda Ospedaliera Cittadella, Padova, Ospedale Umberto Parini, Aosta,
5
6
7
Villa Sofia, Palermo, Casa di Cura Madonna della Salute, Portoviro, Istituto Clinico Humanitas,
8
Rozzano, Casa di Cura Villa Verde, Fermo, Italy
The objective of this study was to demonstrate the safety and efficacy of a percutaneous paddle lead
TM
for SCS. Percutaneous paddle lead (S8 series
leads, St Jude Medical) was implanted using
TM
introduction system for percutaneous implantation (Epiducer
lead delivery system, St. Jude
Medical). Our case studies reports about 75 percutaneous leads in 71 patients implanted in 8 different
Pain Centre in Italy. 12 patients suffered a negative trial and explanted the percutaneous paddle. After
24 months from the implant VAS and all dimensions of IPQ decreased in significant way (p< . 001). At
the last follow-up 65% stopped their pain medications. Regarding the body area coverage, in the
axial-lumbar area it was in a range of 90-100% and in the radicular and lower limbs was in a range of
80-90%. In 1 case during the implant dural surgical injury occurred. The dislocation of the
percutaneous paddle is a rare adverse event (1%). Our Cases reported only 1 dislocation after an
accidental shock. In 3 cases we recorded a dislocation soon after the post-operative period (3%). In
all the cases has been possible to operate with positive outcome without explantation. Four patients
explanted the paddle after 5 weeks with no adverse events. 1 patient explanted after 6 months
without adverse events too. Paddle lead was more invasive than cylindrical but without more
complications. Our data showed that SCS paddle leads was an efficient alternative for patients with
FBSS.
57
PAIN, OBESITY AND DIABETES: A ROLE FOR SPINAL ADIPONECTIN?
1
2
N. Bourwis , T. Iannitti , S. Dolan
1
1
2
Life Sciences, Glasgow Caledonian University, Glasgow, School of Biomedical Sciences, University
of Leeds, Leeds, UK
The adipose tissue derived cytokine, adiponectin, has significant anti-inflammatory properties in a
variety of disease conditions. Adiponectin is reduced with obesity and in type 2 diabetes patients; both
conditions associated with development of co-morbid pain. This study set out to characterise
expression of adiponectin and its receptors AdipoR1 and AdipoR2 in spinal cord in rodent models of
genetic obesity (Zucker rats), and type 2 diabetes, and determine if changes are associated with
alterations in nociceptive pain.
Responses to thermal and mechanical stimulation of the hindpaw were assessed in adult male Zucker
fatty rats and lean littermates (n = 6/group), and in adult male Wistar rats injected intraperitoneally
(i.p) with low dose of streptozotocin (STZ; 30 mg/kg; (n = 6/group), and fed a high fat diet for 12 week
(model of type 2 diabetes); control rats were fed a normal diet and received vehicle citrate buffer (i.p).
Expression of adiponectin and AdipoR1 and 2 mRNA was measured in rat spinal cord using real-time
PCR.
Diabetic but not obese Zucker rats displayed significant hypersensitivity to acute thermal and
mechanical nociceptive stimuli. A significant decrease in adiponectin mRNA was detected in spinal
cord from both diabetic (8 fold decrease; P < 0.05 vs. control rats) and obese Zucker rats (2.4 fold
decrease; P < 0.05 vs. lean rats). AdipoR1 and R2 mRNA remained unchanged in both models.
These data suggest that adiponectin may contribute to altered sensory processing at the spinal level,
through activation of AdipoRs, to modulate pathological pain.
58
NEURONAL ORGANIZATION IN THE DORSAL HORN OF THE SPINAL CORD: LONG TERM
EFFECTS OF PAINFUL STIMULI IN THE NEONATAL PERIOD
1
1
1
2
N.L.B. Machado , E.C. Carmo , L.S. Sanada , A.L.R. Oliveira , V.P.S. Fazan
1
1
Department of Nerosciences and Behavioral Neurosciences, School of Medicine of Ribeirão Preto,
2
Ribeirão Preto, Department of Anatomy, Cell Biology and Physiology and Biophysics, University of
Campinas, Campinas, Brazil
Scientific evidence accumulated over the past 15 years indicates substantial differences between
genders with regard to responses to painful stimuli, as well as to pain treatment. We analyzed the
neuronal distribution in the dorsal horn of the spinal cord of adult rats submitted to painful stimuli
during neonatal period. Fourteen Wistar rats with 180 days of life were separated in 4 groups:
pain male group (n=4),
control male group (n=4),
pain female group (n=3) and
control female group (n=3).
The pain group was stimulated with a needle on the right paw and the control group was stimulated
with a cotton swab on the right paw, being both groups stimulated twice a day for 15 days. We
evaluate the hyperalgesia of both groups with Von Frey Monofilament and a specific calibrated
forceps. The analysis of the neuronal distribution in the dorsal horn of the spinal cord was performed
by counting Nissl stained neurons with a computer software. Statistic tests were applied, significances
were accepted when
p < 0.05. We observed that the pain male group presented a hyperalgesia in the right hindpaw when
compared to the control group, but no differences were found in the neuronal counting in the spinal
cord between the groups. Our results suggest that noxious stimuli during neonatal period are capable
of changing the sensorimotor system in the long term in male rats, with no detectable alteration on
neuronal configuration in the dorsal horn. Increasing the number of animals studied will confirm these
findings.
59
NEURONAL ACTIVITY AND DRUG PROFILES IN NEUROPATHIC PAIN MODELS IS
INFLUENCED BY ANAESTHESIA RATHER THAN NERVE INJURY METHODOLOGY
1
2
1
S. Hirsch , A.H. Dickenson , L. Corradini
1
Dept. CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der
2
Riß, Germany, Departments of Neuroscience, Physiology and Pharmacology, University College
London, London, UK
Preclinical neuropathic pain research relies on animal models like chronic constriction injury (CCI).
We addressed the question whether spinal wide dynamic range (WDR) neuronal activity and drug
effects investigated with the rat chronic constriction Injury (CCI) model resemble those known from
the rat spinal nerve ligation (SNL) pain model (Suzuki et al, 2008). In-vivo electrophysiological
experiments in the study of neuronal activity and drug actions require general anaesthesia.
Anaesthetics however alter the neuronal network and might interfere with the molecular cascades
modulated by the analgesics tested. Thus, we compared results on WDR neuronal activity and drug
effects in rat CCI model under isoflurane anaesthesia or pentobarbital anaesthesia.
When the mu-opioid receptor agonist, morphine, and the sodium channels modulator, gabapentin
were tested, we found that drug profiles and basal neuronal activity partly depend on anaesthesia.
Morphine inhibited WDR neurons activity in CCI rats under both anaesthetic conditions (30-35%
inhibition in multiple endpoints). Gabapentin reduced partially (10% inhibition in spontaneous and
thermally evoked activities) spinal activity when tested under pentobarbital anaesthesia. Interestingly,
a marked inhibitory effect of Gabapentin can be achieved under Isoflurane anaesthesia (30-35%
inhibition in multiple endpoints). Furthermore, results were compared to Chapman et al et al,1998
where inhibitory properties of Gabapentin were tested in a comparable protocol in SNL rats. We could
observe that Gabapentin effect under Isoflurane anaesthesia is consistent between animal models of
neuropathic pain.
Our results suggest that anaesthesia influences electrophysiological results to a greater extent than
the animal model of neuropathic pain.
60
USEFULNESS OF LASER-EVOKED POTENTIALS AND QUANTITATIVE SENSORY TESTING IN
DIAGNOSES OF SPINAL CORD INJURY PAIN: A REPORT OF 2 CASES
G. Landmann, C. Lustenberger, L. Stockinger, A. Ljutow, M. Béchir
Centre for Pain Medicine, Swiss Paraplegic Centre, Nottwil, Switzerland
Objective: We report 2 patients where laser-evoked potentials (LEP) and quantitative sensory testing
(QST) were helpful in the differential diagnosis of spinal cord injury pain.
Methods: Two patients with supposed spinal cord injury pain but no abnormalities on spinal imaging
and normal neurophysiology were investigated with LEP and QST to establish the diagnosis of a
spinal cord lesion.
Results: Patient 1 (P1) had an incomplete quadriplegia sub C2 (AIS D) with burning pain of hands
and feet pronounced on left side while patient 2 (P2) had an incomplete paraplegia sub Th10 (AIS D)
with burning pain perianal and in S2 dermatome of right thigh. In P1 LEP revealed significant
reduction in amplitudes on left hand, consistent with negative and positive sensory signs pronounced
on left in QST. P2 showed impaired sensory and pain thresholds to laser stimuli on right S2
dermatome at the thigh but normal cortical LEP while QST showed bilaterally signs of A-delta-fibre
impairment, central sensitisation on affected side but wind up phenomenon contralateral.
Conclusion: While in P1 LEP result is consistent with a lesion of spinothalamic tract, in P2 a lesion of
spinothalamic tract could not be established as LEP testing revealed only changes in sensory and
pain thresholds. Therefore in presence of pathological LEP result the abnormal QST in P1 can
support the diagnosis of spinal cord injury and related pain but in P2 with normal LEP, QST as a
psychophysical examination may be unspecific and not helpful in diagnosis of spinal cord injury pain.
61
DIFFERENTIAL EFFECTS OF CALCITONIN GENE-RELATED PEPTIDE ON SUPERFICIAL
SPINAL TRIGEMINAL NUCLEUS CAUDALIS NEURONS IN MOUSE BRAINSTEM SLICES
B.E. Nixdorf-Bergweiler, H. van Brederode, F. Zheng, K. Messlinger
Institute of Physiology & Pathophysiology, University of Erlangen-Nuernberg, Erlangen, Germany
Background and aims: The neuromodulator calcitonin gene-related peptide (CGRP) facilitates
nociceptive transmission in the spinal trigeminal nucleus caudalis (Sp5C). The precise mechanism of
this central CGRP action is unknown.
Methods: We made whole-cell recordings from lamina I/II neurons in transverse brainstem slices of
juvenile C57BL/6 mice (7-14 days postnatal). Effects of CGRP application (500 nM) on membrane
potential and firing properties were examined. Suprathreshold current pulses (500 ms) or a series of
step pulses at increasing strength were applied.
Results: We identified four classes of neurons, previously described in superficial laminae of rat and
mice Sp5C, according to their response characteristics to current injection. Neurons showed tonic
(27%) or phasic responses (23%) or had delayed (18%) or single spike response behaviour (18%). In
addition, we identified another class of neurons, which responded to step pulses in a burst-like
manner (14%). A detailed analysis of CGRP effects on membrane potential revealed that tonic cells
(n=6) were depolarized by 3.9±1.4 mV (p=0.04). Phasic neurons (n=5) were hyperpolarized by
1.8±0.5 mV (p=0.03), accompanied by a decrease in spike frequency (60±10%, p=0.02). After
application of CGRP together with the non-selective glutamate receptor blocker kynurenic acid (2
mM), the membrane potential of neurons did not change (n=6).
Conclusions: CGRP exerts differential effects on neurons of different classes in superficial laminae
of Sp5C. Enhanced levels of CGRP may facilitate nociceptive transmission to spinothalamic neurons
but may attenuate the effect of inhibitory interneurons. CGRP effects on membrane potential most
likely depend on glutamate receptors.
62
HYPERALGESIC EFFECT OF PHENTOLAMINE SUBDURAL IN RATS
1
2
1
1
1
1
O.C. Pires , D.C. Callegari , E. Constantino , R.B.C. Braga , A.F.M. Gimbo , A.A. Souza , N.C.
1
1
Cusma-Pelógia , I.P. Posso
1
2
Medicine, Taubate University, Taubate, Medicine, Faculdade de Medicina do ABC, Santo Andre,
Brazil
Background and aims: Phentolamine is a competitive antagonist at alpha1 and alpha2 receptors
+
and also blocks 5-HT receptors and K channels. Objective was to evaluate the analgesic or
hyperalgesic effect of phentolamine subdural in rats.
Methods: After Ethics Committee approval subdural catheter was inserted in 28 Wistar halothaneanesthetized rats. They were divided into four groups. In formalin control (GCF) and in formalin active
(GAF) groups pain was induced by modified formalin test with injection of 50ml of 2% formalin into the
dorsum of hindpaw. In plantar incision control (GCI) and plantar incision active (GAI) groups pain was
induced by the Brenner test of hindpaw plantar incision and evaluation of hyperalgesia using Von
Frey filaments. Before induction of pain was injected 10ml of saline by subdural catheter in the
controls group and 20mg of phentolamine in 10ml of saline by subdural catheter in the actives group.
Results: In the intermediate phase of the formalin test the number of flinching was: GCF 10.94±10.60
and GAF: 25.71±17.90 (P=0.003). Phentolamine presented hyperalgesic effect in the intermediate
phase of the formalin test. Phentolamine also presented hyperalgesic effect by plantar incision test. In
the first day the scores were GCI: 4.62±0.30 and GAI: 3.63±0.39 (P=0.014), on the third day the
scores were GCI: 4.85±0.66 and GAI: 3.62±0.54 (P=0.0006) and on the fifth day the scores were GCI:
5.00±0.28 and GAI: 4.22±0.67 (P=0.0359).
Conclusions: Phentolamine 20 mg subdural showed hyperalgesic effect possibly by inhibiting spinal
pain modulation probably due to alpha1 adrenergic receptor stimulation.
63
THE UP-REGULATION OF MICRORNA 23B IN SPINAL CORD IS ASSOCIATED WITH THE
INDUCTION OF NEUROPATHIC PAIN IN RAT
P.-H. Tan, C.-C. Liu
Anesthesiology, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan R.O.C.
Background and aims: MicroRNAs (mirs) are small noncoding transcripts that can control
expression of protein-coding mRNAs at the posttranscriptional level and play an important role in
regulating synaptic plasticity. Significant up-regulation of mir-23b in spinal cord was noted in our
microarray miRNA profiling in neuropathic pain. We hypothesized the up-regulation of mir-23b play a
role in the induction of neuropathic pain. In this study, we examined the antinociception produced by
inhibition of mir-23b in spinal cord for neuropathic pain.
Methods: Spinal nerve ligation (SNL) was performed to induce neuropathic pain. In treatment groups,
2 nmole locked nucleic acid (LNA) LNA-mir-23b inhibitor or scrambled LNA-mir-23b inhibitor were
administered 3 days after SNL. Behavioral tests were performed before or 5 days and 10 days after
injection of LNA-mir-23b inhibitor or scrambled LNA-mir-23b inhibitor. The spinal cord was dissected
for analysis of mir-23b after behavioral test performed at 5 and 10 days after injection of LNA-mir-23b
inhibitor or scrambled LNA-mir-23b inhibitor. The analysis of mir-23b was preformed by quantitative
real-time polymerase chain reaction and in-situ hybridization.
Results: Significant increase of mir-23b was noted in spinal cord of rats received SNL only.
Intrathecal injection of 2 nmole LNA-mir-23b inhibitor could effectively diminish SNL-induced allodynia
and thermal hyperalgesia on day 5 and day 10 after injection of LNA-mir-23b inhibitor and decrease
the expression of miRNA-23b in spinal cord.
Conclusions: This study provides evidence that SNL induces up-regulation of mir-23b in spinal cord
and inhibition of mir-23b produces antinociceptive effect for neuropathic pain.
64
SPINAL D-AMINO ACID OXIDASE CONTRIBUTES TO MECHANICAL PAIN HYPERSENSITIVITY
INDUCED BY SLEEP DEPRIVATION IN THE RAT
1
2
2
H. Wei , G. Nian , Y.-X. Wang , A. Pertovaara
1
1
2
Physiology, Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland, King's Lab,
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
Background and aims: We studied the hypothesis that spinal D-amino acid oxidase (DAAO) that is
expressed by astrocytes and that has been reported to promote tonic pain in various
pathophysiological conditions play a role in 'physiological' hypersensitivity induced by rapid eye
movement sleep deprivation (REMSD).
Methods: The experiments were performed in healthy rats with a chronic intrathecal (i.t.) catheter.
Pain behavior was assessed by determining limb withdrawal response to repetitive stimulation of the
hind paw with a calibrated series of monofilaments. REMSD of 48 h duration produced a significant
mechanical hypersensitivity. After REMSD, the animals were treated i.t. with a DAAO inhibitor or
vehicle. Three structurally different DAAO inhibitors were tested in this study: 6chlorobenzo[d]isoxazol-3-ol (CBIO), sodium benzoate, and 5-methylpyrazole-3-carboxylic acid (AS057278).
Results: CBIO (1-3 µg), sodium benzoate (30-100 µg) and AS-057278 (3-10 µg) produced doserelated antihypersensitivity effects in sleep-deprived animals. In control animals (with no sleep
deprivation), the currently used doses of DAAO inhibitors failed to produce significant changes in
mechanically evoked pain behavior.
Conclusions: The results indicate that among spinal pain facilitatory mechanisms that contribute to
sleep deprivation-induced pain hypersensitivity is DAAO that is known to be located in the astrocytes,
where it could produce ROS acting on the pronociceptive TRPA1 channel expressed by central
terminals of primary afferent nerve fibers in the spinal dorsal horn.
65
COMBINED USE OF INTRATHECAL THERAPY AND SACRAL NERVE STIMULATION FOR
POST-LAMINECTOMY SYNDROME
A.E. Yakovlev, L.M. Fields, A. Parmentier
Comprehensive Pain Managment of the Fox Valley, Neenah, WI, USA
Introduction: Intrathecal pumps (ITP) have become a valuable tool in managing intractable
noncancer pain. Intrathecal therapy have proven successful at improving pain patients with severity
and decreased oral opioid consumption. Two years after ITP pump placement patients low back and
lower extremity pain was no longer adequately covered with the ITP, despite rotation of opioid, and
addition of bupivacaine.
Methods: This 54 year old man presents with a long history of chronic low back and leg pain due to
post-laminectomy syndrome (PLS) failed conservative therapy , multiple injections and spinal cord
stimulator trial. The decision was made to proceed with implantation of an ITP after efficacious trial.
Unfortunately, pain in both leg and low back started to come back, despite escalating titration of
intrathecal hydromorphone and additional bupivacaine. Decision to proceed with SNS trial. During the
trial two 8 electrode leads were inserted through sacral hiatus into epidural space with final lead
positioned between S1 and S4. Patient reported resolution in the pain in his low back and legs doring
the trial and after implantation of SNS.
Results: The patient reports sustained pain relief in low back and bilateral lower extremities with the
use of intrathecal therapy and SNS. Patient is no longer receiving any oral opioid analgesics.
Conclusions: SNS should be considered in patients with intrathecal delivery systems to cover
intractable pain when all other treatments fail. SNS can be an effective adjunct therapy to an
intrathecal system.
66
SCS FOR BILATERAL FOOT PAIN RELATED TO BANNAYAN-RILEY-RUVALCABA SYNDROME
1
2
A. Yakovlev , L.M. Fields , A. Parmentier
1
2
2
Comprehensive Pain Management of The Fox Valley, Appleton, Comprehensive Pain Managment
of the Fox Valley, Neenah, WI, USA
Introduction: Bannayan-Riley-Ruvalcaba Syndrome (BRRS) is characterized by craniofacial,
somatic, motor and intellectual development conditions, skin, gastrointestinal system, neoplasms,
skeletal system and other abnormalities are experienced in different degrees. This case reports on a
22 year old female with a predominant skeletal abnormality - gigantism of the feet causing intractable
bilateral combined joint and neurologic foot pain.
Methods: We report successful spinal cord stimulator trial and permanent implantation in a 22 year
old female patient with bilateral foot pain diagnosed with BRRS.
Results: A-23-year-old female presenting to our clinic after seeing several orthopedic specialists who
indicated no surgical intervention was indicated. She was facing permanent disability due to the pain,
after conservative therapy failed, neuromodulation was considered. During the trial two 8 electrode
leads placed in the posterior epidural space the tip at the levels of T8-9, and T 10. Both leads were
connected to a temp generator. This resulted in report of greater than 90% relief of pain, and no use
of immediate release morphine. Decision was made to proceed with permanent placement at a later
date. Patients reports the stimulation covers 100% relief of pain and 60% decrease of Morphine use
within the first four months post operative, and 100% pain relief and no use of Morphine six months
after implant.
Conclusions: Spinal cord stimulation for treatment of foot pain related to BRSS is is a treatment that
can decrease and/or eliminate use of opioids in the young adult while improving quality of life is worth
further exploration.
67
OPTIMIZING AN OPIOID FOR PCA DELIVERY: THE CLINICAL IMPORTANCE OF CST ½ AND
T½KE0
1
2
T.-J. Gan , M.A. Royal , P.P. Palmer
3,4
1
2
3
Anesthesiology, Duke University Medical Center, Durham, NC, Clinical Affairs, Clinical, AcelRx
4
Pharmaceuticals, Inc., Redwood City, Anesthesiology, University of California San Francisco, San
Francisco, CA, USA
Background and aims: Traditional PK can be misleading with opioids. The t½ke0 (plasma/CNS
equilibration half-life) better predicts PD effects. The CST ½ (context-sensitive half-time or time from
Cmax to 50% Cmax) better reflects duration than t½. Rapid redistribution following IV administration
®
(CST½ 8.4min) means a short duration of action for IV sufentanil PCA. Sufentanil NanoTab PCA
System (SNPS) optimizes sufentanil delivery.
Methods: Patients self-administer sufentanil 15mcg sublingual (SL) doses (20min lockout) with a
hand-held device. A crossover PK study (Table 1) and randomized repeat dose efficacy and safety
study of SL sufentanil vs. IV PCA morphine (Study IAP309), demonstrate PK/PD parameters of
morphine PCA vs. SL sufentanil.
Results: Compared to IV sufentanil, slower absorption across the SL mucosa results in an 18-fold
longer CST½, avoiding the redistribution limitation with PCA delivery (Table 1). IV morphine has a t ½ke0
of 168min vs. sufentanil 6.2min, suggesting slower onset and possibly delayed AEs. These
differences may explain better pain responses from 1 to 4h (p < 0.01), longer interdosing interval, and
fewer oxygen desaturations (p=0.028) than PCA morphine in Study 309 (n=359) after major surgery.
Conclusions: CST½ and t½ke0 can help choose the best opioid for PCA delivery. SNPS was designed
using these principles.
IV
Sublingual
Buccal
Oral
100
57
78
6
Cmax (pg/mL)
mean
361.1
37.7
53.0
3.3
Tmax (h) median
0.07
0.83
0.85
1.11
Context-sensitive
half-time
0.14
2.50
2.28
2.00
Bioavailability %
[Sufentanil PK Parameters with Routes of Admin]
68
TEMPORAL DYNAMICS AND SPECIFICITY OF THE INTERACTIONS BETWEEN NOCICEPTIVE
AND MOTOR SYSTEMS IN HUMANS
1
1
2
M. Algoet , J. Duque , G. Iannetti , A. Mouraux
1
1
2
Institute of Neuroscience, University of Louvain, Brussels, Belgium, Department of Neuroscience,
Physiology and Pharmacology, University College London, London, UK
Background and aims: The ability to detect, localize and trigger adequate motor responses to
threatening stimuli is a crucial function of nociception. Here, our aim was to characterize the temporal
dynamics and specificity of the interactions between nociceptive and motor systems in humans. We
hypothesized that the occurrence of a nociceptive stimulus should elicit an urge to move the
stimulated limb, which would translate into a specific and time-dependent modulation of motor
excitability within the flexor muscles involved in the withdrawal of the stimulated limb.
Methods: Following the delivery of a brief CO2 laser stimulus to the left or right hand dorsum, motorevoked potentials (MEPs) elicited by concomitant transcranial magnetic stimulation (TMS) of the
left/right primary motor cortices (M1) were recorded from left/right hand flexor and extensor muscles
(first dorsal interosseous, FDI; flexor carpi radialis; FCR, extensor carpi radialis, ECR). The delay
between the nociceptive stimulus and TMS (50, 100, 150, 200, 250, 300, 350, 400, 600, 1000 and
2000 ms), and the hand where the nociceptive stimulus was applied (left, right) was randomized
across trials.
Results and conclusion: At 100 ms, MEPs were enhanced in the flexor muscles of the stimulated
hand, probably reflecting spinal facilitation. From 150-1000 ms, MEPs were reduced in all muscles,
but this reduction was more pronounced and longer lasting in the flexor muscles of the stimulated
hand. This later effect is likely to result from cortical interactions between nociceptive and motor
systems.
69
THALAMIC RESPONSES TO NOCICEPTIVE STIMULI IN HUMANS
1
1
2
1
1
H. Bastuji , M. Frot , S. Mazza , C. Perchet , M. Magnin , L. Garcia-Larrea
1
1
2
CRNL, Neuropain Team, INSERM, U 1028, UMR 5292, LEMC, Université Lumière, Lyon, France
While the main cortical generators of laser-evoked potentials (LEPs) are well characterised now
(operculo-insular cortex and mid-anterior cingulate), those of the thalamus have been scarcely
studied. We report LEPs to nociceptive stimuli recorded in four thalamic nuclei. These results were
obtained in 17 epileptic patients implanted with intracranial electrodes, who received laser stimuli
slightly above nociceptive threshold.
Local early responses (onset 110-150 ms) were consistently recorded in the central lateral nucleus
(CL), the ventro postero lateral nucleus (VPL) and the anterior pulvinar (PuA). They occurred in the
same latency range than that of the posterior insula; their amplitude was twice smaller than that of the
cortical response, except for those of the PuA which could be comparable to that of the insula.
Contrasting with these 3 'early responding' nuclei, the responses in the medial pulvinar (PuM) nucleus
did not develop until 100 ms later, their duration was significantly higher and their morphology
extremely desynchronized. Early responses from VPL, CL and PuA appear to reflect direct postsynaptic responses to spinothalamic projections. Conversely, the delayed response of the PuM -an
associative thalamic nucleus- may reflect cortico-subcortical interactions subserving communication
between cortical associative areas.
70
MODULATION OF NOCICEPTIVE INFORMATION PROCESSING DURING PARADOXICAL
SLEEP: AN INTRACEREBRAL RECORDING STUDY
1
1
1
1
1
1
2
L. Claude , J.-B. Sauzeau , L. Mikula , C. Perchet , M. Magnin , L. Garcia-Larrea , S. Mazza , H.
1
Bastuji
1
2
Central Integration of Pain (Neuropain), Lyon Neuroscience Research Center (CRNL), Laboratoire
d'Étude des Mécanismes Cognitifs (EMC), Lyon, France
Previous studies have shown that laser nociceptive stimulations disrupt sleep in 30% of the cases and
that a late component on scalp EEG may predict arousals. The inconstancy of behavioural reactivity
to nociceptive stimulation may be related to fluctuations in brain activity known to occur during sleep.
The aim of the present study was to analyse the influence of phasic (vs tonic) and slow (vs fast)
thalamic periods on brain and behavioural responses to nociceptive stimuli during paradoxical sleep.
The study was performed with intracranial recordings in two key-structures of the nociceptive matrix:
thalamus and posterior insula.
Nociceptive laser stimulations were delivered on the hand during night-sleep in epileptic patients
implanted with intracranial electrodes. Responses were analysed according to whether stimulations
were delivered
1) during Rapid Eye Movements (REM) (phasic) or without REM (tonic) in 6 patients and
2) during delta or non-delta thalamic activity in 12 patients.
While tonic / phasic REM periods did not influence the insular nociceptive responses, these were
significantly delayed, and lacked late components when the stimulus was specifically delivered during
periods of slow thalamic delta activity. The percentage of arousals was however similar in both
conditions.
Fluctuations of thalamic activity during paradoxical sleep modulated nociceptive information
processing in the insula, but did not influence sleep disruption. Our results suggest that the arousal
threshold is higher than that of changes in posterior insular processing. Insular changes may reflect a
necessary but not sufficient element in a chain of events leading to pain-induced arousal.
71
INHIBITION OF NITRIC OXIDE SYNTHASE IN THE PRELIMBIC CORTEX PREVENTS THE
ANTINOCICEPTION INDUCED BY PANIC-LIKE REACTION ORGANIZED IN THE
HYPOTHALAMUS
1
2
2
R.L. de Freitas , J.E.C. Hallak , J.A.S. Crippa , N.C. Coimbra
1
1
2
Pharmacology, Neuroscience and Behavioural Sciences, Psychiatry Division, Ribeirão Preto
Medical School of the University of São Paulo, Ribeirao Preto, Brazil
The endocannabinoid CB1 and NMDA or AMPA/kainate glutamatergic receptors plays a role into the
prelimbic medial prefrontal (PL) cortex during the elaborations of the innate fear inducedantinociception evoked by intra-medial hypothalamus (MH) microinjection of bicuculline. The aim of
the present work was to investigate if the blockade of neuronal nitric oxide synthase (NOs) in the PL
cortex exerts any effect on the innate fear-induced antinociception induced by GABA-A receptor
blockade into the MH. Male Wistar rats (n=5-8 per group) were used. A guide cannula was
stereotaxically implanted in both PL cortex and MH. Five days after surgery, microinjection of 200 nl of
10% DMSO or Nw-propyl-L-arginine (L-NPA), a NOs inhibitor (at 0.02, 0.04 e 0.08 nmol) into the PL
cortex was performed. After 5 minutes, MH was treated with bicuculline (40ng/200nl), a GABA-A
receptor antagonist, or saline (NaCl, 0.9%; 200nl), following the recording of nociceptive thresholds
(by tail-flick test) after the elicitation of defensive reactions in the open-field test. The inhibition of NOs
in the PL cortex through local microinjections of L-NPA at 0.08nmol was able to decrease the
defensive attention, the defensive immobility, the forward escape behaviour, and defensive backward
movement (P< 0.05, in all cases). PL cortex-pre-treatment with L-NPA (0.08nmol) caused a significant
decrease in the innate fear-induce antinociception elicited by the GABAergic blockade into the MH,
according to one-way ANOVA followed by Duncan's post hoc test. These findings suggest that the
organisation of the instinctive fear-induced antinociception involves the nitric oxide (NO)-mediated
system within the PL cortex.
72
NEUROPATHIC PAIN REDUCES HIPPOCAMPUS-PREFRONTAL CORTEX CONNECTIVITY IN
RATS PERFORMING A SPATIAL WORKING MEMORY TASK
1,2
1,2
H. Cardoso-Cruz , D. Lima , V. Galhardo
1
1,2
2
IBMC - Instituto de Biologia Molecular e Celular, Departamento Biologia Experimental, Universidade
do Porto, Porto, Portugal
Impaired working memory (WM) is observed in chronic pain patients, but the mechanisms and brain
areas underlying this cognitive impairment remain elusive. The medial prefrontal cortex (mPFC) and
dorsal hippocampal CA1 (dCA1) are well known to form an interconnected neural circuit that is crucial
for correct performance in spatial memory-dependent tasks. In this study, we investigated whether the
functional connectivity between these two areas is affected by the onset of an animal model of
peripheral neuropathic pain. We chronically implanted arrays of electrodes in the mPFC and dCA1 of
adult rats and recorded the neuronal activity while performing a spatial WM task consisting in a
reward-based alternation maze. Recordings were performed for 3 weeks, before and after the
establishment of the SNI model of neuropathy. Our results show that the nerve lesion caused a clear
impairment of WM performance that is temporally correlated with changes in the mPFC activity when
the animals navigated between decision points - when memory retention was most needed.
Moreover, the activity of both recorded neuronal populations after the nerve injury increased their
phase-locking in respect to hippocampal theta rhythm. Finally, our data shows that chronic pain
reduces the overall amount of information flowing in the fronto-hippocampal circuit and induces the
emergence of different oscicllation patterns that are well correlated with correct/error performance of
the animal on a trial-by-trial basis. Our results demonstrate that functional disturbances in the mPFCdCA1 connectivity are a relevant cause for pain-related WM deficits.
Supported by: FCT Grant-SFRH/BD/70522/2010, FCT Project-PTDC/SAU-NEU/100773/2008.
73
REDUCED CONNECTIVITY BETWEEN PREFRONTAL CORTEX AND MEDIODORSAL
THALAMUS IS ASSOCIATED WITH SPATIAL WORKING MEMORY IMPAIRMENT IN RATS WITH
INFLAMMATORY PAIN
1,2
H. Cardoso-Cruz , V. Galhardo
1
1,2
2
IBMC - Instituto de Biologia Molecular e Celular, Departamento Biologia Experimental, Universidade
do Porto, Porto, Portugal
The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form interconnected neural
circuits that are important for spatial cognition and memory, but it is unknown if the functional
connectivity between these two areas is affected by the onset of an animal model of inflammatory
pain. To address this issue, we implanted two multichannel arrays of electrodes in the mPFC and MD
of adult rats and recorded local-field potentials activity during a food-reinforced spatial working
memory task. Recordings were performed for three weeks, before and after the establishment of the
pain model. Our results show that inflammatory pain caused an impairment of spatial working memory
performance that is associated with changes in the activity of the mPFC-MD circuit; analysis of partial
directed coherence - PDC - between the two areas revealed a global decrease in the connectivity of
the circuit.
This decrease was observed in a wide frequency range in both frontothalamic and thalamofrontal
directions of the circuit, but is more evident from MD to mPFC. In addition, spectral analysis revealed
significant oscillations of power across frequency bands, namely with a strong theta component which
oscillates after the painful condition onset. Finally, our data revealed that chronic pain induces an
increase of theta/gamma phase-coherence, and a higher level of mPFC-MD coherence, which in
partially conserved across frequency bands. The present results demonstrate that functional
disturbances in the mPFC-MD connectivity are a relevant cause for pain-related working memory
deficits.
Supported by: FCT Grants SFRH/BD/70522/2010, PTDC/SAU-NEU/100773/2008.
74
CONTRIBUTIONS OF THE RVM TO CENTRAL SENSITIZATION ASSOCIATED WITH
OSTEOARTHRITIS
1
1
2
A. Haywood , V. Chapman , G. Hathway
1
2
Arthritis Research UK National Pain Centre, School of Life Sciences, School of Life Sciences,
University of Nottingham, Nottingham, UK
Background and aims: Osteoarthritis joint damage does not always correlate with the severity of
pain, and 15% of patients still experience chronic pain even after joint replacement. We hypothesise
that OA pain involves sites beyond the diseased joint and that supraspinal centres such as the rostral
ventral medulla contribute to the maintenance of OA pain.
Methods: In adult Sprague-Dawley rats, changes in hindlimb weightbearing asymmetry were
quantified up to 28 days post-OA induction. In the carrageenan model of inflammatory pain,
weightbearing asymmetry was assessed for up to 3 hours. Electromyographic (EMG) recordings were
made in MIA and carrageenan treated rats and the effects of DAMGO (30ng/0.5ul, mu-opioid agonist)
inactivation of the rostral ventral medulla (RVM) on EMG responses was determined.
Results: Weightbearing asymmetry was present in the carrageenan model and MIA model of OA
pain, compared to saline controls. EMG studies demonstrated a reduction in threshold to evoked
withdrawal responses and an increase in the stimulus-response curve function (indicating spinal
hyper-excitability) in carrageenan and MIA-treated rats, compared to controls. Intra-RVM
administration of DAMGO significantly (P< 0.01) attenuated EMG responses.
Conclusions: The behavioural pain responses exhibited by both models are accompanied by
increases in the magnitude of EMG responses as well as an enhanced facilitation of the spinal reflex
responses. This finding is consistent with clinical evidence for central sensitization in people with OA.
Inactivation of the RVM by DAMGO significantly reduced EMG responses, which supports previous
literature that facilitation of spinal reflexes involves descending control from the RVM.
75
CORTICAL VANILLOID RECEPTORS TYPE-1 IN NEUROGLIAL NETWORK: A NEW TARGET
FOR STUDYNG NEUROPATHIC PAIN
1,2
1,2
3
1,2
M.C. Marrone , M. Giustizieri , S. Marinelli , S. Marinelli
1
2
European Brain Reseach Institute - Fondazione Rita Lavi Montalcini, IRCCS Fondazione Santa
3
Lucia, CNR - National Research Council, Cell Biology and Neurobiology Institute, Rome, Italy
Neuropathic pain (NP) can induce impairment of cognitive processes that in turn modulates pain
perception. Indeed, strong evidence indicates that NP results in a hyperexcitability and structural
changes of brain areas involved in pain i.e. the anterior cingulate cortex (ACC).
This study focuses on the basic mechanisms of NP at the level of ACC. In particular, we investigate
the functional role of transient receptor potential vanilloid type 1 (TRPV1) in “normal” and NP
conditions (chronic constriction injury murine model, CCI).
We find that cortical spontaneous glutamatergic neurotransmission is higher in CCI than in sham
mice. Conversely, GABAergic transmission is reduced in mice suffering from NP. Moreover, in
physiological conditions TRPV1 is exclusively expressed in the microglia of various brain areas
involved in pain perception, including the ACC. In parallel, patch clamp recordings show that TRPV1mediated presynaptic increase of glutamatergic transmission onto ACC PNs is blocked by
minocycline (an anti-inflammatory agent which prevents microglial activation) and occluded by
lipopolysaccharide (a promoter of microglia hyperactivity). This indicates that activation of microglial
TRPV1 modulates glutamatergic neurotransmission. Curiously, in CCI mice we observed a
phenotypic shift of TRPV1 expression, such that in these mice it is also found in neuronal cytoplasm
of PNs. Accordingly, activation of TRPV1 by capsaicin directly affects PN excitability by inducing an
inward current. This may in part accounts for the increased cortical excitability in NP.
Altogether these data suggest that also in the brain TRPV1 maybe a key target to investigate pain
mechanism.
76
CONNECTIVITY ANOMALIES IN CHRONIC PAIN MODELS
1
2
1
S. Nencini , A.G. Zippo , M. Valente , G. Biella
1
1
2
Bio-Medicine, National Research Council - Institute of Molecular Bioimaging and Physiology,
Segrate, Italy
Background and aims: Chronic pain (CP) is a sensory disorder accompanying many pathological
conditions with different modal, magnitude or temporal features. Our aim is to identify connectivity
anomalies as common feature of diverse CP conditions.
Methods: Three CP animal models (Inflammatory, Seltzer, and Bennett-Xie models) in comparison to
control (CR) have been used. Simultaneous massive electrophysiological extracellular recordings
(light gaseous anesthesia and curarization) were carried out by multielectrode matrices from the
Thalamus Ventrobasal complex and the Primary Somatosensory Cortex. Firing rates and correlation
coefficiencies were estimated. The effective functional connectivity between the recorded neurons
was evaluated by using Directed Information along with the clustering coefficient and the
characteristic path length of graphs obtained from the recordings. We further investigated the
redundancy in spiking activity of each neuronal couple using the Kullback-Leibler divergence.
Results: Firing rates and correlation coefficients both on single neurons and Multi Unit Activity
revealed no significant differences between CR and CP animals, relevant, on the converse, using
segregation and integration parameters.
Conclusions: In these experiments we have shown that different models of CP show shared
neurodynamic features well distinguishable from CR in the reduction of information segregation and
the decrease of information integration. In a clinical perspective, we could thereby envisage CP as
disrupted functional connectivity. This could address to radical revision of CP diagnostic and
therapeutic appraisals CP.
Acknowledgements: Thanks to Dr. Jose' M. Carmena for his kind gift of the program for assessing
functional connectivity.
This work has been funded by the PON project pon01_01297
77
CHANGES OF SPONTANEOUS OSCILLATORY ACTIVITY TO TONIC HEAT PAIN
1
2
1
W. Peng , L. Hu , Z. Zhang , Y. Hu
1
1
2
The University of Hong Kong, Hong Kong, Hong Kong S.A.R., Southwest University, Chongqing,
China
Transient painful stimuli could induce the suppression of alpha oscillatory activities and the
enhancement of gamma oscillatory activities that could also be greatly modulated by attention. Here,
we attempted to characterize the change of cortical activities during tonic heat pain perception and
investigated the influence of directed attention on these response. We collected 5-minute long
continuous EEG data from 38 healthy volunteers under four conditions presented in counterbalanced
order:
(A) resting condition;
(B) innoxious-distracted condition;
(C) noxious-distracted condition;
(D) noxious-attended condition.
The effects of tonic heat pain stimulation and selective attention on oscillatory neuronal activities were
investigated by comparing the EEG power spectra among the four experimental conditions, and the
relationship between spectral power difference and subjective intensity of pain perception was also
tested. The change of oscillatory activities in condition D was characterized by alpha oscillation power
decrease over contralateral-central electrodes and widespread increase of gamma oscillation power
with maximal distribution over frontal-central and ipsilateral-central electrodes. Importantly, the
significant correlation between spectral power difference and subjective intensity of pain perception
was observed at contralateral-central electrodes within alpha band, and at prefrontal-central and
ipsilateral-posterior electrodes within gamma band. Since EEG responses in the alpha and gamma
frequency band were affected by attention in different manners, they are likely related to different
aspects of the multidimensional sensory experience of pain. The observed contrlateral-central alpha
suppression may reflect more about high-cognitive process, while the widespread gamma
enhancement may reflect the summary effects of low-level stimulus-related process and high-level
subject-driven cognitive process.
78
CROSS FREQENCY COUPLING BETWEEN THETA AND GAMMA OSCILLATIONS DURING
NOCICEPTION IN RAT ELECTROENCEPHALOGRAPHY
1
2
1
3
3
3
3
J. Wang , D. Li , X. Li , G. Xing , F. Liu , J. Cai , Y. Wan
1
National Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing,
3
Institute of Electrical Engineering, Yanshan University,, Qinhuangdao, Department of Neurobiology,
Neuroscience Research Institute, Peking University, Beijing, China
2
Background and aims: In electroencephalography (EEG) study, high frequency oscillation, gamma
frequency (40 - 70 Hz) oscillations were reported to participate in pain processing; moreover, slow
frequency oscillation, theta frequency (4 - 8 Hz) oscillations were also involved in pain processing.
Theta oscillation regulates long range interaction while gamma activity is assumed to be the reflection
of local neural networks. Importantly, it were reported that theta activity always modulated gamma
activity by phase-amplitude coupling in event-related oscillations. Pain processing requires integrating
several aspects of nociceptive information. Therefore, our aim is to test whether the cross-frequency
coupling between theta-gamma involve in pain processing.
Methods: We recorded multichannel ECoGs of rats when laser nociceptive stimulation applied to
their feet. Then, gamma activity with wavelet spectrum analysis in the pain-related oscillations was
investigated. Further, the coupling between the phase of oscillations in several frequency's bands and
the amplitude of gamma oscillation were investigated.
Resutls: It was found that induced gamma power increased starting 200 ms after nociceptive
stimulation onset (Figure 1). Significant coupling between theta phase and gamma amplitude was
found over frontal and parietal region after nociceptive stimulation (Figure 2). It indicated there is
theta-gamma phase-amplitude coupling during pain processing.
[Figure 1]
[Figure 2]
Conclusions: Our results suggest that cross frequency coupling between theta and gamma is
involved in nociception processing.
79
PERSISTENT POSTSURGICAL PAIN IS BOTH PREDICTABLE AND PREVENTABLE: A
RANDOMISED CONTROLLED TRIAL
S. Anwar, J. Rahman, C. Sharma, A. Hemming, R. Langford
Pain and Anaesthesia Research Centre, Barts Health NHS Trust, London, UK
Background and aims: The development of Persistent Postsurgical Pain (PPP) is an increasingly
recognized phenomenon. The prediction and prevention of associated nervous system changes has
however been limited by conflicting study design.
Methods: We have carried out the largest QST (Quantitative Sensory Testing) study in surgical
patients as part of a triple-blind randomized controlled trial and have randomized 150 patients
undergoing standardized elective cardiac surgery to either:
1. Pregabalin preoperatively and continued twice daily for 14 days.
2. Pregabalin, as above, as well as low-dose ketamine infusion after surgery.
3. Both drugs as placebo.
Results: Our results show a significant effect of pregabalin alone in preventing pain at three and six
months postoperatively.
We demonstrate a link between anxiety and catastrophizing and subsequent chronic pain. Our QST
assessments reveal the ability of dynamic challenges to the nervous system at the time of surgery,
namely Conditioned Pain Modulation (CPM) as well as temporal and spatial summation, to predict
long-term pain. We also confirm the poor predictive power of static measures of mechanical pain
alone.
Conclusions: This study reveals the potential benefit of preventive analgesia in patients experiencing
moderate to severe surgical pain and links this with both peripheral and central nervous system
changes during this period. This has translational potential in terms of preoperative risk stratification of
patients for PPP, as well as the perioperative use of agents that may modulate these processes,
particularly in high-risk patients.
80
PROTECTIVE EFFECTS OF DF2593A, A SELECTIVE C5AR (C5A RECEPTOR) ALLOSTERIC
MODULATOR, IN MOUSE INFLAMMATORY PAIN MODELS
1
2
1
L. Brandolini , M.M. Teixeira , A. Aramini , G. Bianchini
1
1
2
Research and Development, Dompé S.p.A., L'Aquila, Italy, Departamento de Bioquímica e
Immunologia, Instituto Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte,
Brazil
Background and aims: The role of the C5a/C5aR signaling in the genesis of inflammatory pain is
well characterized. This study aims to evaluate the in vitro selectivity and potency of DF 2593A, a
novel C5aR allosteric modulator, and its in vivo efficacy in acute and chronic inflammatory models of
pain.
Methods: The functional in vitro activity of the molecule was carried out by using C5a-induced PMN
chemotaxis.The in vivo efficacy of DF 2593A in preventing mechanical hypernociception was
investigated in zymosan and Complete Freund's adjuvant (CFA) models in mouse.
Results: DF2593A potently inhibited human and mouse PMN migration induced by C5a (IC 50 = 8.0 ±
0.1 nM and IC50 = 3.0 ± 0.6 nM). Oral administration of DF2593A (1 mg/kg) greatly attenuated
mechanical allodynia at 24 h post-dose in the Zymosan model and completely abolished (90%
inhibition) neutrophil migration in the joints. Similarly, the oral chronic administration of DF2593A
reduced CFA-induced chronic mechanical hyperalgesia.
Conclusions: In the present study, we firstly identified a novel and selective C5a allosteric modulator,
DF2593A, that potently inhibited C5a induced human and mouse PMN migration in vitro. Then we
investigated the compound effects in several acute and chronic inflammatory pain models. DF2593A
was able to provide relief in mechanical allodynia in both the investigated models. These findings
enforces the hypothesis that C5aR blockade may be a novel potential approach in reversing
enhanced mechanical sensitivity in inflammatory pain conditions and suggest C5aR as an innovative
target for the therapy of chronic pain.
81
THE ROLE OF N-PALMITOYETHANOALAMIDE IN INHIBITION OF THE CARRAGEENAN
INDUCED INFLAMMATORY PAIN RESPONSE
1
1,2
1
1,3
S. Assaw , V. Chapman , A.J. Bennett , G.J. Hathway
1
2
3
School of Biomedical Sciences, Arthritis Research UK Pain Centre, Laboratory of Developmental
Nociception, University of Nottingham, Nottingham, UK
Background and aims: The fatty acid amide N-Palmitoyethanoalamide (PEA) is an endogenous
PPAR-α agonist, which has analgesic and anti-inflammatory effects. Activation of toll-like receptors
(TLRs) by substances such as carrageenan, activates intracellular signalling pathways which upregulate the expression pro-inflammatory genes, such as cytokines and chemokines which can
sensitize nociceptive pathways. The aim of this study was to investigate the mechanisms by which the
PEA reduces carrageenan-induced inflammatory pain behaviour.
Methods: Rats received intraplantar injection of 2% carrageenan and hind-limb weight bearing and
paw volume were assessed post-injection. The effects of injection of PEA (50 µg/ml) or vehicle 30
minutes before carrageenan injection on pain behaviour and paw volume was determined. Plantar
skin samples were collected 2 hours post-carrageenan injection, mRNA purified and TaqMan Lowdensity Arrays were used to quantify gene expression. Immunofluorescence was used to determine
number and activation state of immune cells in the paw.
Results: PEA significantly reduced carrageenan-induced pain behaviour 2 hours post-injection,
hindpaw oedema was unaltered. PEA significantly reduced recruitment of monocytic cells whereas
neutrophil numbers were unaltered. Gene expression analysis indicated differential effects of PEA on
expression of pro-inflammatory and other genes involved in innate immune response.
Conclusions: The differential effect of PEA on immune cell recruitment and gene expression
indicates an effect on specific pathways rather than a general anti-inflammatory effect of PEA in the
carrageenan model. This may suggest that the analgesic effects of the nuclear receptor PPAR-α arise
from a targeted regulation of specific components of the inflammatory signalling process.
82
INVOLVEMENT OF Μ-OPIOID RECEPTORS IN ANTINOCICEPTIVE ACTION OF BOTULINUM
TOXIN TYPE A
1
1
2
L. Bach-Rojecky , V. Drinovac , I. Matak , Z. Lacković
1
2
2
University of Zagreb Faculty of Pharmacy and Biochemistry, University of Zagreb School of
Medicine and Croatian Brain Research Institute, Zagreb, Croatia
Background and aims: Recent experimental evidence demonstrated retrograde axonal transport
and suggested the central origin of antinociceptive effect of botulinum toxin type A (BTX-A). However,
the mechanism of BTX-A central antinociceptive action is unknown. In this study we investigated the
potential role of opioid system in BTX-A's antinociceptive activity.
Methods: Male Wistar rats were used in experiments (5-6 per experimental group). The effect of
opioid antagonist naltrexone on antinociceptive activity of BTX-A was assessed in formalin-induced
inflammatory pain. BTX-A was injected into the plantar surface of the hindpaw five days before
formalin injection, while naltrexone was injected subcutaneously (0.02 - 2 mg/kg) 30 min before
nociceptive testing. To investigate the effects of naltrexone and BTX-A on neuronal activation in
spinal cord, c-Fos expression was immunohistochemically examined.
Experiments were approved by the Ethical Committee of the University of Zagreb, School of Medicine
and were conducted according to the European Communities Council Directive (86/609/EEC).
Results: Peripheral BTX-A (5 U/kg) pre-treatment significantly reduced the number of nocifensive
behaviors during second phase of formalin-induced pain (p< 0.001). Naltrexone dose-dependently
reduced the antinociceptive effect of BTX-A. Naltrexone (2 mg/kg) also prevented the reduction of cFos expression in the dorsal horn in BTX-A treated animals (p< 0.05).
Conclusions: These results provide first insights into the mechanism of BTX-A's central
antinociceptive activity suggesting the involvement of endogenous opioid system.
Supported by: Croatian Ministry of Science, Education and Sport.
83
EFFECTS OF THE PRO-RESOLVING LIPID MEDIATOR LIPOXIN A4 ON NEUROPATHIC PAIN
FOLLOWING SPINAL CORD INJURY IN RATS
A. Cadete Martini, S. Forner, G.A. Rae
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil
Background and aims: The majority of traumatic spinal cord injury (SCI) patients develop chronic
central pain syndromes. Inflammatory responses to SCI have been associated to onset of neuropathic
pain via activation of a broad spectrum of factors and signaling pathways. Lipoxin A4 (LXA4), an
eicosanoid endowed with anti-inflammatory and pro-resolution properties, exerts neuroprotective and
antihyperalgesic effects. The present study aims to assess the potential therapeutic effect of LXA4 on
SCI-induced pain.
Methods: Spinal cord hemisection at the left side of T10 was carried out in anesthetized adult male
Wistar rats. At 4 and 24 h after SCI, rats received two intrathecal LXA4 (150 or 300 pmol) or vehicle
injections. Mechanical sensitivity of hind paws and recovery from motor impairment were evaluated
weekly up to 4 weeks after SCI using 4.56 and 5.18 Von Frey hairs and the Basso, Beattie and
Bresnahan locomotor scale, respectively.
Results: Sham-operated animals showed normal mechanical responsiveness and motor activity after
the surgery. SCI significantly increased the frequency of responses to mechanical stimulation with
4.56 Von Frey monofilament only on contralateral hind paw on days 7, 14, 21 and 28. The mechanical
responsiveness to 5.18 Von Frey hair was increased on ipsilateral hind paw on days 7, 14, 21 and 28.
Both concentrations of LXA4 significantly attenuated the mechanical sensitivity changes induced by
SCI. LXA4 also potentiated the locomotor recovery on days 7 and 14.
Conclusion: These results suggest that LXA4 might provide effective pain relief in subjects afflicted
by neuropathies following spinal cord injury.
84
FREQUENCY-TAGGING OF STEADY-STATE EVOKED POTENTIALS TO EXPLORE THE
CORTICAL REPRESENTATION OF NOCICEPTIVE INPUT IN THE HUMAN BRAIN
E. Colon, A. Mouraux
Université Catholique de Louvain, Brussel, Belgium
Whether the cortical processing of nociceptive input relies on the activity of nociceptive-specific
neurons or whether it relies on the activity of non-specific neuronal populations remains a matter of
intense debate. Here, we address this question using EEG “frequency-tagging” of steady-state
evoked potentials (SS-EPs) combined with an intermodal selective attention paradigm to test whether
the cortical processing of nociceptive input relies on nociceptive-specific neuronal populations which
can be selectively modulated by top-down attention. Specifically, we hypothesized that if the cortical
processing of nociceptive and non-nociceptive sensory inputs involves distinct neuronal populations,
selective attention would selectively enhance the SS-EPs elicited by the attended stream of sensory
input. Conversely, if the cortical processing of the two sensory inputs involves the same neuronal
populations, selective attention would indistinctly enhance the responses elicited by the attended and
unattended streams of sensory input. Trains of nociceptive and vibrotactile stimuli (experiment 1) and
trains of nociceptive and visual stimuli (experiment 2) were applied concomitantly to the same hand. A
target detection task ensured that participants focused their attention on one of the two sensory
modalities. We found that selectively attending to nociceptive or vibrotactile somatosensory input
indistinctly enhanced nociceptive and vibrotactile somatosensory SS-EPs, whereas selectively
attending to nociceptive or visual input independently enhanced the SS-EP elicited by the attended
stream of sensory input. These results indicate that the processing of nociceptive input relies on
neuronal populations that are also involved in processing tactile input, but distinct from the neuronal
populations involved in processing visual input.
85
EFFECTS OF THE CARRIER FREQUENCY OF INTERFERENTIAL CURRENT IN PATIENTS WITH
CHRONIC NONSPECIFIC LOW BACK PAIN: A RANDOMISED CONTROLLED TRIAL
1
1
1
2
J.B. Corrêa , L.O.P. Costa , N.T.B.D. Oliveira , K. Sluka , R.E. Liebano
1
1
Master's and Doctoral Programs in Physical Therapy, Universidade Cidade de São Paulo (UNICID),
2
São Paulo, Brazil, Graduate Program in Physical Therapy and Rehabilitation Science, University of
Iowa, College of Medicine, Iowa City, IA, USA
Background and aims: Low back pain is an important public health problem that is associated with
poor quality of life and disability. Among the electrophysical treatments, the evidence on the use of
interferential current (IFC) parameters for decreasing pain remains insufficient. The aim of this study
th
was to evaluate pain after each treatment sessions (30 minute of stimulation and 20 minutes after
stimulation) and the pressure pain threshold (PPT) after 12 sessions treatment.
Methods: A three-arm randomised controlled trial with patient and assessor blinded to the group
allocation. Patients with chronic, nonspecific low back pain from outpatient physical therapy clinics in
Brazil. The patients were randomly allocated into 2 groups: IFC 1 kHz (n=15) or IFC 4 kHz (n=16).
The interferential current was applied three days per week (30 minutes per session) over four weeks.
Results: The IFC 1 kHz presented higher reduction of pain during the treatment compared with IFC 4
th
kHz in the 30 minute of stimulation (p = 0.016). No significant differences were found between
groups 20 minutes after the session has ended (p = 0. 396). There was no difference in mean pain
thresholds between the groups after 12 sessions treatment (IFC 1 kHz p= 0.0547) and (IFC 4 kHz p=
0.1728).
Conclusions: The results suggest that 1 kHz carrier frequency has a more pronounced analgesic
effect immediately after IFC application.The authors thank the financial support obtained from
Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Brazil.
86
5-HT2A AND 5-HT2C SEROTONERGIC RECEPTORS OF THE DORSOMEDIAL AND
VENTROLATERAL COLUMNS OF THE PERIAQUEDUCTAL GREY MATTER MODULATE THE
POST-ICTAL ANTINOCICEPTION
R.L. de Freitas, R.C. de Oliveira, R. de Oliveira, T. Paschoalin-Maurin, N.C. Coimbra
Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Ribeirao Preto, Brazil
It has been described the involvement of opioid, cholinergic, serotonergic and noradrenergic
mechanisms in organisation of the antinociception that follows tonic-clonic seizures. However, the role
played by each serotonergic receptor subtypes found in the periaqueductal grey matter (PAG)
columns, such as the dorsomedial (dmPAG) and the ventrolateral (vlPAG) columns, in the elaboration
of antinociception that follows tonic-clonic seizures has not been elucidated. The present work
investigated the participation of serotonergic receptors of the dmPAG and vlPAG columns in seizureinduced antinociception. Male Wistar albino rats were used. Rats had their nociceptive thresholds
determined using the tail-flick test. Five days after stereotaxic surgery, independent dmPAG or vlPAGtreated groups were submitted to sham procedure or microinjection of saline (0.2µL), 10 % DMSO
(0.2µL), cobalt chloride (1mM/0.2 µL; synapse blocker), R-96544 (10nM/0.2mL; 5-HT2A receptors
selective antagonist), or RS-10221 (0.15mg/0.2mL; 5-HT2C receptors selective antagonist). Five
minutes later, the animals were treated with IP-administration of pentylenetetrazole (PTZ at 64mg/kg,
IP), and the nociceptive responses were recorded immediately after seizures until 180 min post tonicclonic convulsions. Microinjections of cobalt chloride into the dmPAG and vlPAG caused an
intermittent local synaptic inhibition and decreased post-ictal antinociception. Both dmPAG and vlPAG
treatment with either R-96544 or RS-10221 also decreases post-ictal antinociception, according to
repeated measures ANOVA followed by Duncan's post hoc test. These findings suggest that the
serotonergic neurotransmission, recruiting both 5-HT2A and 5-HT2C serotonergic receptors in dmPAG
and vlPAG columns, plays a critical role in the elaboration of post-ictal antinociception.
87
OPPOSITE ROLE PLAYED BY DORSOMEDIAL HYPOTHALAMUS 5-HT1A RECEPTOR ON
DEFENSIVE BEHAVIOURS AND FEAR-INDUCED ANTINOCICEPTION
A.F. Biagioni, R.C. De Oliveira, H. Zangrossi Junior, N.C. Coimbra
Pharmacology, Universidade de São Paulo, Ribeirão Preto, Brazil
Background: The serotonergic system has been suggested to be involved in modulation of panic
attacks and pain. The aim of the present study was to investigate the involvement of 5-HT1A
serotonergic receptor in defensive behaviours and in fear-induced antinociceptive responses
organised by dorsomedial hypothalamus (DMH) neurons.
Methods: Male Wistar rats (n=6 or 8) were pre-treated with microinjections of WAY-100635 (0.74
nmol), 8-OHDPAT (16 nmol) or saline into the DMH. After 10 minutes, bicuculline (40 ng/ 0.2 µL) or
physiological saline was also microinjected into the DMH. Each rat was placed in the open-field test
where the defensive behaviour was recorded during 10 minutes. Posteriorly, tail-flick latencies were
measured for 60 minutes.
Results: One-way ANOVA showed that bicuculline increases the frequency and duration of escape
(F(2,19)=12,84; F(2,19)=11,37; P< 0.001, respectively). DMH Pre-treatment with 8-OHDPAT impaired the
frequency and duration of escape (F(2,19)=12,84; F(2,19)=11,37; P< 0.01, respectively). The DMH
treatment with WAY-100635 did not show any difference in escape behaviour (P>0.05). Furthermore,
WAY-100635 impaired the expression of fear-induced antinociception (F(3,19) ranging from 1.12 to
7.71; P < 0.01). DMH pre-treatment with 8-OHDPAT did not show any significant difference in the
fear-induced antinociception (P>0.05).
Conclusions: Serotonin-mediated system might play an opposite effect modulating panic-like
defensive behaviour and fear-induced antinociception elaborated by DMH neurons.
Acknowledgments: This work was supported by FAPESP (2010/15140-4).
88
THE THERMAL GRILL ILLUSION: THE EFFECT OF SKIN TYPE ON ITS THRESHOLD,
INTENSITY AND QUALITY
R. Defrin, M.D. Shimon
Tel Aviv University, Tel Aviv, Israel
Background and aims: The underlying mechanism of the Thermal Grill Illusion (TGI) is not clear.
One way to study its mediating systems is to compare the characteristics of the TGI between the hairy
and glabrous skin because the two skin types differ in their innervations.
Methods: 20 healthy volunteers participated. For each skin type we measured (with computerized
thermal stimulators) the threshold of innocuous heat (HS), innocuous cold (CS), heat-pain (HP), coldpain (CP) and the TGI (induced with a cooling and a heating probes). The intensity and quality of the
TGI was also measured.
Results: In both skin types, 89% of subjects reported TGI induced burning-pain. In both skin types,
the threshold of the TGI was higher than the thresholds of WS and CS and lower than the thresholds
of HP and CP. The threshold of WS and CS did not differ between the two skin types however the
thresholds of HP, CP and the TGI (p< 0.01 for all) were higher in the glabrous than the hairy skin, with
no differences in intensity and quality of the TGI between the two skin types.
Conclusions: Considering the differential innervations of the two skin types (lack of low threshold
AMH nociceptors in the glabrous skin), the differences in thermal thresholds found, and the values of
the thresholds, it appears that thermal receptors as well as low-threshold thermonociceptors mediate
the TGI. It also appears that spatial summation of thermal information from both channels onto central
multireceptive neurons underlie the TGI.
89
ENDOTHELIN ETA AND ETB RECEPTORS ROLE IN NEUROPATHIC PAIN FOLLOWING SPINAL
CORD INJURY
S. Forner, A. Cadete Martini, G.A. Rae
Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil
Background and aims: Spinal cord injury (SCI) is a devastating neurologic disorder that
compromises motor, sensory, autonomic functions. Endothelins are a family of peptides that exert
their biological effects via distinct receptors, endothelin A (ET AR) and endothelin B (ET BR) involved in
sensory changes in inflammatory and neuropathic pain. However, their role in nociception following
SCI remains to be elucidated.
Methods: Adult male Wistar rats had SCI by inflating an embolectomy catheter at T 10 level. We
evaluated the sensitivity of the animals to mechanical and thermal stimulation of the paws on days 2,
7, 14, 21 and 28 after SCI.
Results: The frequency of responses to mechanical stimulation of forepaws was unchanged at any
time point, but that of hind paws was increased at 14, 21 and 28 days. A reduction in withdrawal
latency to heat stimulation of forepaws was detected 7 and 14 days post-SCI and of hind paws at
days 14 and 21. The upregulation of ET AR expression in spinal cord occurred 21 days post injury
when compared to sham-operated group, but ETBR expression was not altered. ETAR mRNA level
th
was increased in the spinal cord on days 7, 14, 21 and 28 days and on DRG on the 7 day post-SCI.
st
Treatment with BQ-123 (ETAR antagonist, i.t.) on the 21 day after SCI reduced mechanical sensitivity
when compared to its vehicle group.
Conclusion: Our results suggest that the blockage of ET AR might constitute an attractive
pharmacological tool for pain treatment after SCI.
90
TRAZODONE ATTENUATES ACUTE AND NEUROPATHIC PAIN BEHAVIOURS
1
1
1
1
2
B. Garrone , A. Amato , S. De Santi , L. Durando , C. Milanese , S. Tongiani
1
2
3
3
In Vivo Preclinical Development, Preclinical Development, R&D Director, ACRAF S.p.A., Santa
Palomba, Italy
Antidepressant drugs are widely used in the treatment of chronic pain either as adjuvants for or alone.
Trazodone is a multifunctional drug used for the treatment of major depressive disorders, which has
been shown to modulate serotonergic transmission. It has been suggested that its debated
antinociceptive effect could be related to an increased activity of the descending inhibitory fibers or
alternatively to the attenuation of the increase in descending facilitatory inputs, since in both these
conditions 5-HT receptors play a key role. Aim of the present work is to better characterize the
analgesic activity of trazodone using different experimental pain models.
Trazodone was tested in animals on thermal (hot plate), chemical (writhing test), postoperative
(incisional pain test) or neuropathic (chronic constriction injury) pain behaviours in the dose range of
0.1-100 mg/kg po. All animal-use procedures conformed to the guidelines of the European
Community's Council for Animal Experiments.
In acute pain conditions, trazodone produced a dose-dependent antinociceptive effect in both hot
plate (ED50=9.6mg/kg) and writhing tests (ED50=1.2mg/kg). In the incisional pain, vehicle treated
mice displayed profound mechanical allodynia which was significantly reduced in a dose-dependent
manner by trazodone treatment (ED50=13.4mg/kg). Finally, when neuropathic pain was induced in
rats by sciatic nerve ligation, a weak but significant antihyperalgesic effect was observed following
trazodone administration starting from 25mg/kg. These results support a role of trazodone in the
management of pain syndromes. Further investigations on mechanism of action are ongoing in order
to clarify the analgesic potential of trazodone.
91
EXPRESSION OF METABOTROPIC GLUTAMATE RECEPTORS IN RAT TRIGEMINAL
GANGLION NEURONS AND SATELLITE GLIAL CELLS: IMPLICATION IN CRANIOFACIAL PAIN
D.B. Larsen, C. Bleis, G.I. Kristensen, L.I. Akisheva, A. Kandiah, V. Panchalingam, T. Afzali, M.S.
Andersen, J.N. Poulsen, J.C. Laursen, P. Gazerani
Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark
Background and aims: Glutamate, an essential pain mediator, interacts with ionotropic and
metabotropic glutamate receptors (mGluRs). Presence of mGluRs in trigeminal ganglion neurons and
satellite glial cells (SGCs) and their contribution in pain mechanisms have not been well documented.
Here we investigated the expression of mGluRs in trigeminal ganglion neurons and SGCs to provide
better insights into possible roles of these receptors in craniofacial nociceptive transmission.
Methods: Trigeminal ganglia were isolated from adult male Wistar rats (n=6). Initially
immunohistochemistry was performed to determine the expression of mGluR1a, mGluR2/3, and
mGluR8 on neurons and SGCs in vivo. Next, SGCs were isolated from the TG and
immunocytochemistry was conducted to confirm in vivo findings on SGCs.
Results: In vivo, an estimated 35.1 ± 6.0% of TG neurons were identified as mGluR1α positive, 39.9
± 7.7% as mGluR2/3 positive, and 55.6 ± 6.3% of the neurons were mGluR8 positive. Majority of the
neurons expressing either of the mGluRs were estimated to have a mean diameter of 33-36 µm.
Trigeminal SGCs were only immunoreactive for mGluR8. This observation was further confirmed in
vitro, where the majority of isolated SGCs were determined to be mGluR8 positive.
Conclusions: Results of the present study clearly indicated that mGluR1α, 2/3, and 8 are expressed
in both small and medium-sized trigeminal neurons, while SGCs only express mGluR8. This novel
finding shed more light on craniofacial nociceptive transmission and may suggest a cross talk
between neurons and SGCs through these metabotropic receptors.
92
CISPLATIN-EVOKED PGE2 RELEASE FROM TRIGEMINAL SATELLITE GLIAL CELLS, IS
MEDIATED THROUGH P-38 MAPK RESULTING IN ELEVATED EXPRESSION OF COX-1
1
1
1
2
1
F. Larsen , J.N. Poulsen , M. Henriksen , M. Nøhr , M. Duroux , P. Gazerani
1
2
3
3
Laboratory for Cancer Biology, Laboratoriet for Neurobiologi, Center for Sensory-Motor Interaction,
Department of Health Science and Technology, Aalborg University (AAU), Aalborg, Denmark
Background and aims: Glial cells have been recognized as novel contributors in development of
chemotherapy-induced peripheral neuropathy (CIPN), which is a severe debilitating condition
affecting patients with different types of cancer. One of the commonly employed chemotherapeutic
agents is Cisplatin (CIS), which is also associated with development of CIPN. It is not known whether
and how CIS would interact with trigeminal satellite glial cells (SGCs) with a potential link to CIPN in
orofacial cancers. We have previously shown that CIS is a p-38 MAPK activator; and significantly
increases PGE2-release from isolated SGCs; and that SKF86002 (SKF), a p-38 MAPK inhibitor,
significantly reduces CIS-induced PGE2 release. Hence, this study is aimed at elucidating pathways
mediating CIS-evoked PGE2-release, by investigating COX-1 gene-expression in rat trigeminal
SGCs.
Methods: From trigeminal ganglia of adult male Wistar rats (n=5), SGCs were isolated and seeded
2
into culture (100,000 per cm ). COX-1 gene-expression was determined on lysates from control, CISand SKF-treated cultures by PCR technique.
Results: A significant increase in COX-1 gene-expression was observed in CIS-treated SGCs
compared to the control (p< 0.01). SKF significantly attenuated COX-1 gene-expression in the CIStreated SGCs
(p< 0.01).
Conclusion: These findings indicate that increased COX-1 gene-expression following CIS, is partly
mediated through the p-38 MAPK pathway since SKF could efficiently reverse COX-1 geneexpression. Using p-38 MAPK inhibitors (e.g. SKF), to inhibit COX-1 gene-expression following CIS,
may suggest a novel strategy to block PGE2-release from SGCs. This may prove useful in future
management of orofacial related CIPN following CIS-therapy.
93
CISPLATIN-EVOKED PROSTAGLANDIN E2 RELEASE IS NOT INFLUENCED BY CULTURE TIME
OF TRIGEMINAL SGCS UP TO 3 WEEKS
1
1
2
J.N. Poulsen , M. Duroux , J.C. Laursen , P. Gazerani
1
2
2
Laboratory for Cancer Biology, Center for Sensory-Motor Interaction, Department of Health Science
and Technology, Aalborg University, Aalborg, Denmark
Background and aims: Isolated satellite glial cells (SGCs) from sensory ganglia, like the trigeminal
ganglia, may provide a platform to investigate pattern and substance release following activation or
inhibition of these cells in response to various compounds. Such an approach might help identifying
the role of SGCs in sensory transmission (e.g. nociception) and screening drugs with potential
modulatory role on activated SGCs under pathological conditions. We have previously shown that
Cisplatin-evoked release of prostaglandin E2 (PGE2) from cultured SGCs, which might eventually
contribute to chemotherapy-induced neuropathy. Here, we investigated the influence of prolonged
culture time on Cisplatin-evoked PGE2 release from SGCs.
Methods: Trigeminal SGCs were isolated from adult male Wistar rats (n=5). After 7, 14, and 21 days
2
in culture, SGCs were seeded in culture plates (100,000 per cm ) and treated for 8 hours with vehicle
or Cisplatin (66 µM). The PGE2 concentration was determined by ELISA analysis.
Results: Cisplatin significantly increased release of PGE 2 compared with control (p< 0.05). This
phenomenon was not influenced by time, although a tendency of increased PGE 2 release was
observed as a function of time in culture, this tendency was not statistically significant (p>0.05).
Conclusion: We found that Cisplatin-evoked PGE2 release is not influenced by SGCs culture time up
to 21 days. This finding is highly valuable since prolonged culture time gives rise to a larger cell yield,
which alternatively would enhance experimental reproducibility and reduce number of animals needed
to isolate SGCs while there is no commercial source of these cells available.
94
A MAGNETOENCEPHALOGRAPHIC STUDY ON PAIN-RELIEF BY VIBROTACTILE
STIMULATION
1,2
1
1
1
2
M. Hayamizu , K. Hagiwara , N. Hironaga , K. Ogata , S. Hoka , S. Tobimatsu
1
1
2
Clinical Neurophysiology, Neurological Institute, Anesthesiology and Critical Care Medicine, Faculty
of Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Background and aims: Pain-relief by vibrotactile stimulation (VTS) is a well-known gating
phenomenon. Although the inhibition of the spinal and cortical activities has been reported, the exact
location at cortical level is largely unknown. Therefore, we investigated gating effects on secondary
somatosensory area (SII) by using magnetoencephalography.
Methods: The gating effects on pain by VTS were evaluated by somatosensory evoked magnetic
fields in 7 subjects. Aβ fibers were activated by VTS while Aδ fibers were stimulated by intraepidermal electrical stimulation (IES). Stimuli were delivered to the right forearm, and there were four
different conditions: 1) VTS and IES simultaneously, 2) IES 60 ms prior to VTS, 3) IES alone and 4)
VTS alone. Minimum norm estimates were applied to assess the somatotopic activations. SII was
targeted as the region of interest (ROI) and the activation curves on ROI were compared among the
different conditions.
Results: In making comparison between combined stimulation (1, 2) and sum of the separate
stimulation (3, 4), the attenuations of activation in SII area at 0 ms and 60 ms were found. Apparent
magnitudes of gating effects between 0 ms and 60 ms were not significantly different.
Conclusions: These results suggested the existence of the cross-modal interaction in SII area. Albeit
clarification of functional difference between gating effects at spinal and cortical levels needs further
investigation, our study demonstrated the electrophysiological signature of the gating at the cortical
level.
95
MECHANISMS UNDERLYING CLINICAL EFFICACY OF ANGIOTENSINII TYPE2 RECEPTOR
(AT2R) ANTAGONIST EMA401 IN NEUROPATHIC PAIN: CLINICAL TISSUE AND IN VITRO
STUDIES
1,2
1
1,3
1,3
1,3
4
5
U. Anand , Y. Yiangou , M. Sinisi , M. Fox , A. MacQuillan , T. McCarthy , C. Bountra , Y.E.
2
1
Korchev , P. Anand
1
2
Peripheral Neuropathy Unit, Centre for Clinical Translation, Nanoscience Research Laboratory,
3
Division of Medicine, Imperial College London - Hammersmith Hospital, London, Peripheral Nerve
4
Injury Unit, Royal National Orthopaedic Hospital, Stanmore, UK, Spinifex Pharmaceuticals,
5
Melbourne, VIC, Australia, Structural Genomics Consortium, University of Oxford, Oxford, UK
Background and aims: The clinical efficacy of AT 2R antagonist EMA401, a novel peripherallyrestricted analgesic, was reported recently in post-herpetic neuralgia (McCarthy et al., 2012). While
AT2R is known to be expressed by human nociceptors, the levels of its endogenous ligands
Angiotensin II (AngII) and AngIII in clinical neuropathic pain tissues, and their signalling pathways,
require investigation.
Methods: We immunostained AngII, AT2R and TRPV1, and quantified AngII and AngIII by ELISA.
The in vitro effects of AngII, NGF and EMA401 on expression of p38 and p42/44 MAPK were
measured using immunofluorescence.
Results: AngII immunostaining was observed in c. 80% of small/medium diameter neurons in control
(n=6) and avulsion injured (n=10) human DRG, but not large neurons i.e. similar to TRPV1. AngII was
co-localised with TRPV1 and AT2R in human DRG and in vitro. AngII staining by image analysis
showed no significant difference between control (n=12) and injured human nerves (n=13). AngII
levels by ELISA were also similar in control human nerves (4.09 +/- 0.36 pmol/g, n=31), injured nerve
trunks (3.99 +/- 0.79 pmol/g, n=7), and painful neuromas (3.43 +/- 0.73 pmol/g); AngIII levels were
undetectable or below < 0.03 pmol/g. AngII and as expected NGF increased signal intensity of p38
and p42/44 MAPK in cultured DRG neurons; EMA401 partially reversed AngII effects.
Conclusions: The major AT2R ligand in human peripheral nerves is AngII, and its levels are
maintained in injured nerves. EMA401 may act on autocrine/paracrine mechanisms in peripheral
nerve terminals to reduce neuropathic pain signalling in AngII/NGF/TRPV1-convergent pathways.
96
PERCEPTION OF PAIN IN THE VEGETATIVE STATE: A HEART RATE VARIABILITY PILOT
STUDY
F. Riganello, M.D. Cortese, F. Arcuri, M.E. Pugliese
Research in Advanced Neurorehabilitation, S. Anna Institute, Crotone, Italy
Background and aims: The involvement of high-order associative brain structures beyond the
primary somatosensory cortex in response to noxious somatosensory stimuli in the vegetative state
(VS) is questioned. Aim of the study was to measure by heart rate variability the sympathovagal
changes during noxious stimulation.
Method: Heart Rate Variability measures (5-min baseline; 2-min after nociceptive stimulus; 5-min
post-stimulus) were obtained by EKG from 12 controls and 10 vegetative state subjects. The noxious
stimulus was applied on the fingernail bed by algometer at intensity above threshold. The EKG was
processed in the time and frequency domains.
Results: VS and controls differed in baseline by the relative power of the low frequency heart rate
variability peak (RPwLF), by the signal entropy (ApEn) in nociception phase, and by the pkHF, nuLF,
RPwLF and RPwHF values in the post-stimulus phase. Differences between the baseline and
nociception epochs were observed in the ApEn of both groups (z< -3.784, p< 0.0001) and in the
controls' low frequency peak (pkLF) (z=-1.972, p=0.049). Baseline and post-stimulus differed by the
high frequency peak (pkHF) in VS. A good patients vs. controls classification in the nociception vs
post-stimulus phases was detected in the pkHF and ApEn variables (4.419< Wald< 8.193; 0.004< p<
2
0.036) (binary logistic regression: correct classification: 72.7% and 87.5%, R Nagelkerke= 0.418 and
0.569 respectively; Hosmer-Lemeshow: p>0.320).
Conclusion: The study confirm the applicability of heart rate variability methods in the functional
classification of the VS subjects' neurovegetative responsivity and as a method to monitor their
reactivity to noxious stimuli.
97
IS DESCENDING INHIBITORY PAIN MODULATION MEDIATED BY OPIOIDS? A PROSPECTIVE
STUDY IN PATIENTS WITH CHRONIC PAIN TREATED WITH HYDROMORPHONE
1,2
3
3
2,3
E. Suzan , D. Pud , R. Treister , M. Haddad , E. Eisenberg
1
1,2
2
The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel, Institute
3
of Pain Medicine, Rambam Health Care Campus, Faculty of Social Welfare and Health Sciences,
University of Haifa, Haifa, Israel
Background and aims: The effect of opioids on the descending inhibitory pain pathways remains
controversial. Conditioned pain modulation (CPM) and offset analgesia (OA) are considered as
representing paradigms of descending inhibitory pain modulation in humans. The aim of the current
prospective open-labeled study was to test the effects of hydromorphone therapy on descending
inhibitory pain modulation, measured by changes from baseline in the magnitudes of CPM and OA.
Methods: Thirty patients with chronic neuropathic (radicular) pain (21 men, 9 women, mean±SD age
of 47.5 ± 13.1 years) received four weeks of oral hydromorphone treatment at an individually titrated
doses (mean±SD dose of 11.6±4.8 mg; range 4-24 mg/per day). CPM and OA were assessed before
and after a four-week hydromorphone treatment. CPM was assessed by subtracting the response to a
painful phasic heat stimulus administered simultaneously with a conditioning cold pain stimulus from
the response to the same heat stimulus administered alone . The OA paradigm consisted of a train of
three-temperature stimuli (T1=49°C [5s], T2= 50°C [5s], T3=49°C [20s]). The magnitude of OA was
quantified by subtracting minimal pain scores obtained during T3 from the maximal pain scores
obtained during T2.
Results: CPM scores changed from baseline of 17.7± 20.6 to 21± 20.4 following treatment and OA
scores changed from 7.8±20.5 to 9.7±14.6. Wilcoxon signed rank test indicated that these changes
were not significant (CPM: p=0.416; OA: p=0.436).
Conclusions: These results suggest that the descending inhibitory pain modulation, manifested in
humans by CPM and OA, is likely mediated by non-opioid mechanisms.
98
A NOVEL ANIMAL MODEL OF CHEMOTHERAPY-INDUCED COLD ALLODYNIA REVEALS A
CRUCIAL ROLE FOR NAV1.6 IN PERIPHERAL COLD PAIN PATHWAYS
1
2
3
4
1
5
1,5
J. Deuis , K. Zimmermann , A. Romanovsky , L. Possani , P. Cabot , R. Lewis , I. Vetter
1
2
School of Pharmacy, University of Queensland, Woolloongabba, QLD, Australia, Department of
3
Physiology and Pathophysiology, University of Erlangen-Nuernberg, Erlangen, Germany, St.
4
Joseph's Hospital and Medical Center, Phoenix, AZ, USA, Instituto de Biotecnologia, Avenida
5
Universidad, Cuernvaca, Mexico, Institute for Molecular Bioscience, University of Queensland, St
Lucia, QLD, Australia
Background and aims: Oxaliplatin, a third-generation platinum chemotherapeutic agent, is
associated with acute cold-induced peripheral dysaesthesias and paraesthesias including cold
allodynia. The pathophysiological mechanisms underlying acute oxaliplatin-induced cold allodynia
remain unclear, and the symptom is poorly managed in the clinic.
Methods: We estalbished a novel animal model of chemotherapy-induced cold allodynia based on
the intraplantar injection of oxaliplatin and assess cold allodynia by quantifying the number of paw
flinches at 10 degrees Celsius.
Results: We found that intraplantar oxaliplatin rapidly induced a long-lasting cold allodynia that was
unaffected in Nav1.8, TRPA1 or TRPM8 knockout animals but was completely abolished by
tetrodotoxin. Pharmacological characterisation with subtype-selective ion channel modulators
revealed a role for Nav1.6 in oxaliplatin-induced cold allodynia. Consistent with a crucial role for
delayed-rectifier potassium channels in excitability in response to cold, intraplantar administration of
+
the K -channel blocker 4-aminopyridine mimicked oxaliplatin-induced cold allodynia and was also
inhibited by Nav1.6 blockers. Intraplantar injection of the Na v1.6-activator Cn2 elicited spontaneous
pain, mechanical allodynia and enhanced 4-aminopyridine-induced cold allodynia.
Conclusions: These findings provide behavioural evidence for a crucial role of Nav1.6 in multiple
peripheral pain pathways including cold allodynia.
99
CHRONIC INTRACEREBROVENTRICULAR LIPOPOLYSACCHARIDE INJECTION INCREASES
GENE EXPRESSION OF CONNEXIN30 AND 32 IN RAT HIPPOCAMPUS
M. Abbasian
Islamic Azad University, Urmia, Iran
Introduction: Gap junctions are intercellular membrane channels that provide direct cytoplasmic
continuity between adjacent cells. This communication can be affected by changes in expression of
gap junctional subunits called Connexins (Cx). Changes in the expression and function of connexins
are associated with number of neurodegenerative diseases. Hippocampus has particular vulnerability
to damage and consequent inflammation. Cx30 is mainly expressed in Astrocytes and Cx32 is
expressed in Olygodandrocytes and GABAergic interneurons in hippocampus. In this study, the effect
of Bacterial Lipopolysaccharide (LPS) induction on Cx30 and 32 expressions in rat hippocampus was
evaluated.
Material and method: LPS (2.5µg/rat) was infused into the rat cerebral ventricles for 14 days. The
mRNA and protein levels of Cx30 and 32 were measured by Real Time PCR and Western Blot at the
st
th
th
1 , 7 and 14 injection.
th
Results and conclusion: Cx30 and 32 mRNA were significantly increased respectively after 14 and
th
7 injection of LPS, however no changes in Cx30 and 32 protein levels were found. Increased Cx30
and 32 mRNA expressions might contribute to the survival of the GABAergic neurons and increase
their synchronized inhibitory synaptic transmission and reduce vulnerability of neurons to
inflammatory insults. This finding suggests expression of Cx30 and 32 were occurring in
transcriptional level. However, post-translational processes are thought to be major factor in
regulating Cxs functional coupling. LPS might affect the stability and half-life of Cx proteins.
Nevertheless, effect of LPS on Cx30 and 32 channel gating should be determined to further elucidate
effect of LPS on GJC.
100
P610T MUTATION IN NAV 1.7 SODIUM CHANNEL IN A FAMILY WITH PRIMARY
ERYTHERMALGIA
1,2,3
J. Avez-Couturier
1
1,4
1
, S. Dalmas , A. Deprez , L. Vallée
2
2
3
Child Pain Consultation, Paediatric Neurology, CHRU de Lille, CIC-IT 807 CHRU Lille,
Anaesthesia and Intensive Care, CHRU de Lille, Lille, France
4
Backgrounds and aims: Primary erythermalgia (PE) is a painful genetic disorder of autosomal
dominant transmission, characterized by attacks of symmetrical pain, elevated skin temperature and
redness in the extremities. PE is associated with mutations in SCN9A gene coding for voltage-gated
sodium-channel Nav1.7, expressed in dorsal root ganglion (DRG) and sympathetic ganglion neurons
(Drenth, 2007). Several SCN9A mutations have been described. P610T mutation was not considered
as a pathogenic mutation or not at a highly penetrant way (Samuels, 2008). We report a family (father
and daughter) sharing the same clinical characteristics with P610T mutation in SCN9A.
Methods: The proband is a 3-year-old girl. She had, since her first year, typical attacks of
erythermalgia. She had received several drugs (carbamazepine, gabapentine, nicardipine,
propanolol) with no efficacy. Her father also had typical symptoms of PE but does not use any drugs.
Patients were screened for SCN9A gene mutations (fluorescent sequencing analysis).
Results: Heterozygous sequence variation at nucleotide C1828A in exon 12 (P610T) was detected in
the proband and her father. Her mother was not carrying the mutation. We proposed to treat her with
mexiletin. With 12 mg/kg/day mexiletin total improvement was obtained at 6 months and maintained at
1 year. Her father refused to take any drug.
Conclusion: P610T mutation in SCN9A gene should be considered as a pathogenic mutation for
primary erythermalgia. Based on our experience this mutation could be perfectly mexiletin sensitive.
101
FIBROMYALGIA AND DNA METHYLATION- A PILOT STUDY
1,2
1
3
3
1
1
D.C. de Andrade , R. Galhardoni , H.C. Vieira , T.C. Ferraz , C.S. Dale , R.D.L. Pagano , G.R.
3
1
1
1
3
Gouveia , D.T.R.M. Fernandes , H.H.S. Kaziyama , M.J. Teixeira , H.P. Brentani
1
2
Pain Center, Department of Neurology, Medicine School of University of São Paulo, Instituto do
3
Câncer do Estado de São Paulo Octavio Frias de Oliveira, Psychiatry Institute, Clinics Hospital,
Medicine School of University of São Paulo, São Paulo, Brazil
FM is a complex disorder. Different lines of evidence point to genes, epigenetic mechanisms and
gene-environmental interactions contributing to the risk of FM. One of the mechanisms of epigenetic
control of the genome is DNA methylation. DNA Methylation is one of the most important mechanisms
to modulate gene expression. We performed a whole-genome methylation analysis in FM patients
and healthy controls to investigate differentially methylated genes in these two groups.
Method: Blood from 25 FM patients and 25 paired healthy subjects (HS) was collected. FM patients
underwent cortical excitability evaluation with rTMS and filled out the McGill and Fibromyalgia Impact
Questionnaire and the Brief Pain Inventory. Extraction of DNA was performed by the salting-out
method. Methylation pattern of the genome was made by the Illumina Infinium HD assay (480K). Data
was analyzed by Genome Studio Data Analysis Software and the IMA-package, with t-Student test
and Benjamini-Hochberg (BH) for false discovery ratio (FDR < =0.05).We used two different software
DAVID and WebGestalt (hipergeometric test and FDR < =0.05) searching for hyper represented
pathways. We found 24 genes differently methylated in FM patients. The hyper represented pathways
included cytokine-cytokine receptor interaction-(CXCL5, MPL, TNF-RSF19), Adherence junction(NLK,CTNNA2), MAPK signaling-(NLK, PRKCG, MECOM), Arrhythmogenic right ventricular
cardiomyopathy-(ARVC), Leukocyte Transendothelial Migration-(PRKCG, CTNNA2), Cancer
pathways-(PRKCG, CTNNA2), vascular smooth muscle contraction-(PRKCG, CALD2), tight-junction(PRKCG, CTNNA2), Calcium-Signaling pathways-(RYR2, PRKCG). These data suggest that different
methylation patterns exist in genes related to immunity and inflammatory response in FM. It remains
to determined whether these findings would have a classification use or provide insight into its
mechanisms of disease.
102
EFFECT OF PERSIAN SHALLOT EXTRACT ON GLUCOKINASE (GCK), GLYCOGEN
PHOSPHORYLASE AND PHOSPHOENOLPYRUVATE CARBOXYKINASE (PEPCK) GENES
EXPRESSION IN DIABETIC RATS
1
2
H. Ghasemi , I. Salehi , Y. Moradi
1
3
2
3
Hamadan University of Medical Sciences, Physiology, H. U. Puerto Real, Hamadan, Molecular
Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
There has been a growing interest in hypoglycaemic agents from natural products, especially those
derived from plants. In the current survey, hypoglycaemic properties of Persian shallot (Allium
hirtifolium Boiss) was evaluated by studying mRNA expression levels of the key enzymes involved in
carbohydrate metabolism in liver, Glucokinase (GCK), phosphoenolpyruvate carboxykinase (PEPCK),
and glycogen phosphorylase. Thirty two male rats were divided into 4 groups of 8, diabetic groups
received 100 and 200 mg/kg Persian shallot extract, diabetic control and normal control received
0.9% saline for 30 days. At the end of the experimental period blood and liver samples were collected.
FBS and insulin levels were measured and followed by analysis of the gene expression by Real-Time
PCR based methods. Findings indicated that the Persian shallot significantly reduces the FBS level in
parallel with slight enhancement of insulin in diabetic rats' serum. Investigations of gene expression
showed that Persian shallot gently increased GCK and glycogen phosphorylase but decreased
PEPCK gene activity, in diabetic rats. In conclusion, the data suggest that Persian shallot is an
effective hypoglycaemic agent, the observed effect may be via its ability to enhance insulin secretion
and GCK gene expression and to decrease hepatic glucose output by reducing PEPCK.
103
IL-1Α AND IL-1RN GENE POLYMORPHISMS ARE ASSOCIATED WITH INCREASED PAIN AND
SLOWER RECOVERY FOLLOWING LUMBAR DISC HERNIATION
1,2
2,3
4
2,3
1,5
A. Moen , E.I. Schistad , L.J. Rygh , C. Røe , J. Gjerstad
1
2
National Institute of Occupational Health, Department of Physical Medicine and Rehabilitation, Oslo
3
4
University Hospital, Ullevaal, Faculty of Medicine, University of Oslo, Oslo, Department of
5
Anesthesiology and Intensive Care, Haukeland University Hospital, Bergen, Department of Molecular
Biosciences, University of Oslo, Oslo, Norway
Background and aims: Radicular pain following lumbar disc herniation may be associated with
release of inflammatory cytokines from the nucleus pulposus (NP). Here, we examine the role of
interleukin-1α (IL-1α) and IL-1 receptor antagonist (IL1-Ra) in this process.
Methods: First, in an animal model mimicking the clinical situation, the effect of NP applied onto the
dorsal nerve roots was studied by spinal electrophysiological recordings and the mRNA expression of
IL-1α and IL-1Ra in the NP tissue was quantified by qPCR. Second, in a total of 252 patients with disc
herniation and radicular pain, we investigated how genetic variability in IL-1α and IL-1RN influence the
one-year clinical outcome measured by visual analogue scale (VAS), McGill Pain questionnaire
(MPQ) and Oswestry Disability Index (ODI).
Result: The animal data demonstrated a significant increase in the nociceptive activity at the spinal
level, and a clear up-regulation of mRNA for IL-1α in the NP tissue already 3 hours after application of
NP onto the nerve-roots. A positive correlation between IL-1α expression and IL1-Ra expression was
also observed. Moreover, the data of the patients revealed that the IL-1α rs1800587 T allele in
combination with the IL-1RN rs2234677 A allele may be associated with higher pain and disability
scores 6 weeks, 6 months and 12 months after disc herniation.
Conclusions: Our findings suggest that genetic variability in IL-1α and IL-1RN may promote
inflammation and increase the risk of a chronic outcome following disc herniation.
104
DORSAL ROOT GANGLIA EXPRESSION OF 5-HT RECEPTOR TYPE 3A IS MODULATED BY
THE TRANSCRIPTION FACTOR PRRXL1 (DRG11)
1,2
1,2
1,2
1,2
C. Monteiro , M. Matos , M. Dourado , D. Lima , V. Galhardo
1
1,2
2
IBMC - Instituto de Biologia Molecular e Celular, Departamento Biologia Experimental, Universidade
do Porto, Porto, Portugal
The paired-type homeodomain transcription factor Prrxl1 (also known as Drg11) is a key regulator of
the differentiation and survival of dorsal root ganglia (DRG) and spinal nociceptive neurons in preand perinatal stages. Prrxl1 knockout mice exhibit abnormalities in DRG-spinal projections, in
superficial dorsal horn structure and reduced nociceptive behaviour in pain tests. We have recently
found that DRG expression of Prrxl1 in adult animals is increased in an inflammatory pain model
raising the possibility that this transcription factor may play a role in pain processing in adulthood.
Microarray analysis (unpublished data) show that expression of the serotonin receptor 3A (Htr3a) is
altered in Prrxl1 knockout mice. Thus, we tested the simultaneous expression of both Htr3a and Prrxl1
in an inflammatory pain model, and if the silencing of Prrxl1 in ND7/23 neuronal cell line would affect
the expression of Htr3a. Our results show that after inflammatory pain (zymosan paw injection) there
is an ipsilateral increase of both genes in DRGs (Prrxl1: 3.05+/-0.38 fold; Htr3a: 2.07+/-0.17 fold). To
silence Prrxl1, ND7/23 cells were electroporated with 10microM of either siPrrxl1 or a non-targeting
siRNA oligonucleotide. After 48h the electroporated cultured cells were collected and immediately
used for RNA extraction. Knockdown levels of Prrxl1 and 5HT3 were assessed by real time PCR. The
silencing using Prrxl1-siRNA resulted in a downregulation of both Prrxl1 (-3.22+/-0.06 fold) and Htr3a
(-2.86+/-0.12 fold). Our results suggest that Prrxl1 has a modulatory role over Htr3a expression in
DRGs.
Study supported by FCT grants PTDC/SAU-NEU/100773/2008, PTDC/SAU-NEU/101995/2008, and
SFRH/BD/28752/2006.
105
CYP2D6 GENOTYPING IN A CHRONIC PAIN POPULATION: IS A FIFTH PHENOTYPE
CLASSIFICATION OF 'MODERATE METABOLISER' REQUIRED FOR CONCORDANCE?
H.E. Radford
1,2,3
3,4
3,4
2,3
2
, K.H. Simpson , S. Rogerson , M.I. Johnson , P. Fitzgerald , S.W. Martin
1
2
2
Pain Management Services, University of Leeds / The Leeds Teaching Hospitals NHS Trust, Faculty
3
4
of Health and Social Sciences, Leeds Metropolitan University, Leeds Pallium Research Group, Pain
Management Services, The Leeds Teaching Hospitals NHS Trust, Leeds, UK
1
Background/aim: The CYP2D6 Activity Score (AS) model is utilised for interpretation of phenotype
2,3,4
from genotype. AS 1.0 can be allocated to Intermediate (IM) or Extensive (EM) metabolisers
; this
contributes to potential misinterpretation in literature and clinically. As part of a larger study chronic
pain patients were genotyped to determine the frequency of phenotypic groups to compare with
reported prevalence in literature and to determine if AS 1.0 should be allocated to Moderate
Metaboliser (MM).
Methods: Caucasians aged 18-80 years were recruited after informed consent (n=64). Salivary DNA
(Oragene•DNA Self-Collection Kit) was processed by KASP™ (Kompetitive Alellen Specific PCR) for
alleles *1,*2,*3,*4,*5,*6, *9, *10, *17, *41 and duplication. Genotypes were identified and allocated AS.
2,3,4
Phenotypic status allocated based on three separate models . Frequencies were compared for
discordance.
Results: Phenotype allocation to Poor Metabolisers (6.25%) and Ultra Metabolisers (1.5%) correlated
2
4
through all models. IMs and EMs varied considerably depending on model from 4.7% IMs to 7.8%
3
3
4
2
and 31.3% ; 61% EMs compared to 84.4% and 87.5% .
[Comparison of AS models]
Conclusion: Discordance in allocation of phenotypic groups according to the model used could lead
to clinical error if therapy depended on knowing CYP2D6 activity. AS 1.0 can be classed as IM or EM,
but has 50% more function than AS 0.5 (IM), and 50% less function than AS 2 (EM). Allocating
phenotypic status MM to AS 1, representing a 50% reduction in activity compared to normal levels
would provide clarity and unify this classification.
106
THE INTERLEUKIN-1Α GENE C>T POLYMORPHISM RS1800587 IS ASSOCIATED WITH
INCREASED PAIN AND REDUCED PRESSURE PAIN THRESHOLD FOLLOWING LUMBAR DISC
HERNIATION
1,2
3
1,2
E.I. Schistad , L.M. Jacobsen , C. Røe , J. Gjerstad
1
3,4
2
Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Ullevaal, Faculty of
3
4
Medicine, University of Oslo, National Institute of Occupational Health, Department of Molecular
Biosciences, University of Oslo, Oslo, Norway
Background: Previous studies have suggested that many inflammatory cytokines, including
interleukin (IL)-1α, may be associated with lumbar radicular pain after disc herniation. In the present
study, we examined how variability of the IL-1α gene affects pain intensity and pressure pain
threshold in patients the first year after disc herniation.
Methods: A total of 122 patients with lumbar radicular pain due to disc herniation were recruited from
Oslo University Hospital, Norway, and followed up at 6 weeks and 12 months. The primary outcome
measures were pain intensity scores for the lower back and legs using a visual analog pain scale
(VAS) and pressure pain threshold (PPT) for the bilateral gluteal muscles. Genotyping was carried out
using a predesigned TaqMan assay for IL-1α rs1800587. The effect of the IL-1α genotype on the VAS
and PPT was analyzed by repeated measure analyses of variance.
Results: The IL-1α gene C>T polymorphism rs1800587 affected both the VAS and PPT scores after
disc herniation. Patients with the CT/TT genotype reported a higher VAS leg pain intensity (p = 0.002)
and also a lower PPT in the gluteal muscles (p = 0.016 bilaterally) compared to patients with the CC
genotype during 1 year of follow-up.
Conclusions: The present data show that the IL-1α CT/TT genotype rs1800587 may be associated
with a high pain intensity and a corresponding low pain threshold in the first year after disc herniation.
107
INCREASED EXCITATORY EFFECTS OF CALCITONIN GENE-RELATED PEPTIDE AND
INCREASED CALCITONIN-RECEPTOR-LIKE RECEPTOR EXPRESSION ON KNEE AFFERENTS
IN AN OSTEOARTHRITIS PAIN MODEL
1
2
3
1
C. Bullock , A. Mobasheri , P. Wookey , S. Kelly
1
2
Arthritis Research UK Pain Centre, University of Nottingham, Loughborough, Veterinary Medicine
3
and Science, University of Nottingham, Nottingham, UK, Welcome Receptor Antibodies, Victoria,
VIC, Australia
Background and aims: Human data indicate a role for calcitonin gene-related peptide (CGRP) in the
peripheral mechanisms of osteoarthritis (OA) pain. Mechanical sensitization of knee afferents in the
monosodium-iodoacetate (MIA) model of OA pain is coincident with increased CGRP expression. We
investigated CGRP effects on mechanical sensitivity of knee joint nociceptors and expression of the
CGRP receptor component calcitonin receptor-like receptor (CLR) on joint afferents in the MIA model.
Methods: Male Sprague-Dawley rats were injected with MIA (1mg/50µl; n=10) or saline (50µl; n=10)
into the left knee. 14 days post-injection rats were anaesthetised and extracellular recordings were
made from knee joint-associated afferents in response to mechanical stimulation (0.16-15g, 5s
each/5mins) and effects of CGRP (0.5, 1µg/100µl, close i.a) were studied. In separate day 14
MIA/saline-injected rats (n=8 each) CLR protein expression was studied by immunohistochemistry in
fluorogold (FG) labelled knee afferent cell bodies.
Results: CGRP (0.5, 1µg) significantly enhanced the magnitude of mechanically evoked responses of
joint afferents in MIA and saline-injected rats and reduced mechanical thresholds in saline-injected
rats. However a significantly greater proportion of joint afferents were sensitized in MIA-injected rats
(90% MIA, 50% saline) and the number of medium and large knee afferents expressing CLR was
significantly increased following MIA treatment.
Conclusion: Joint afferents from osteoarthritic rats exhibit increased sensitivity to the excitatory
effects of CGRP. This increased sensitivity of the osteoarthritic joint to CGRP may at least be in part
mediated by the increase in the number of knee afferents expressing the CGRP receptor component
CLR.
108
INCREASED EPIDERMAL INNERVATION IN CHRONICALLY INFLAMMED SKIN: A CASE
REPORT
1
1
2
M. Buonocore , A.M. Gatti , L. Demartini , C. Bonezzi
1
2
2
Unit of Clinical Neurophysiology, Unit of Pain Medicine, Fondazione Salvatore Maugeri, Pavia, Italy
In normal skin the topical application of capsaicin induces an acute inflammatory response and a wellknown epidermal denervation, but changes in tissue innervation during chronic inflammation is still
matter of debate.
We present here the case of a patient (64 years-old man) who complained of persistent burning pain
in his right thorax after a burn occurred in operating room, during electrosurgery, three years before.
Physical examination showed a large rectangular area of lesioned, erythematous skin in the right
thorax with a central part completely adhered to deep tissues. In this area mechanical sensations
were quite absent, but in all the other parts of the lesioned skin a dynamic mechanical allodynia was
present. In order to better understand the pain mechanism and possibly target the therapy, the patient
underwent thermal quantitative sensory testing and neurodiagnostic skin biopsy both in the allodynic
and in the contralateral, normal skin.
In the allodynic skin, the quantitative sensory testing showed an heat allodynia/hyperalgesia (reduced
heat pain threshold) and the skin biopsy revealed a significant higher epidermal innervation
(epidermal nerve fiber density of 13.2 fibers/mm) compared to the contralateral, normal skin area (6.0
fibers/mm).
In conclusion, this case report seems to suggest that painful chronic inflammation is accompanied by
an increase in tissue innervation. Further studies on larger populations are warranted.
109
NGF SENSITIZES SILENT NOCICEPTORS IN HUMAN SKIN-RESULTS FROM A
MICRONEUROGRAPHY STUDY
1
2
2
B. Namer , R. Rukwied , M. Schmelz , O. Obreja
1
2
2
Dept for Physiology and Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Dept of
Anesthesiology and Operative Intensive Care, University of Heidelberg, Mannheim, Germany
Background and aims: Nerve growth factor (NGF) promotes neuronal survival and outgrowth.
Injected into human skin it provokes long lasting mechanical hyperalgesia.
Methods: Human microneurography was used to investigate single C-fiber properties 3 weeks after
NGF (1 µg/50 µl) administered intradermally at five spots inside the innervation territory of the
peroneal nerve at the foot dorsum. The contralateral foot was injected with saline as control. In
human, two C-nociceptor classes can be separated by microneurography: mechano-responsive (CM)
fibers with less activity dependent conduction velocity slowing (ADS) and mechano-insensitive (CMi)
nociceptors with large ADS.
Results: Mechanical and electrical hyperalgesia restricted to the injection spots was present 3 weeks
after NGF injection.
Microneurography recordings showed:
1. NGF increased the proportion of atypical C-fibers exhibiting axonal properties characteristic of CMi
fibers (i.e., large ADS, slower recovery), but responding to mechanical stimulation.
2. The sensitivity of atypical C-fibers for both electrical and mechanical stimuli was increased after
NGF.
3. These differences were more prominent upon stimulation of the hyperalgesic versus the nonhyperalgesic receptive field of the same parent axon.
Conclusions: These findings corroborate results from NGF-treated pigs, suggesting that long-term
changes of CMi excitation patterns may contribute to NGF-evoked mechanical hyperalgesia. Thereby,
NGF may alter not only signal transduction, but also spike initiation and conduction. The sensitivity
differences between branches of the same parent axon innervating hyperalgesic, respectively nonhyperalgesic areas might suggest that axonal protein synthesis probably contributes to the localized
NGF-evoked hyperalgesia.
Supported by: EGG (EFIC/Grünenthal) grant
110
ULTRAVIOLET-B (UV-B) IRRADIATION ALTERS MECHANICAL SENSITIVITY OF
UNMYELINATED NOCICEPTORS IN THE PIG SKIN, IN VIVO
1
1
1
1
1
1
2
1
F. Werland , M. Hirth , E. Forsch , A. Bistron , R. de Col , R. Rukwied , M. Ringkamp , M. Schmelz ,
1
O. Obreja
1
2
Anesthesiology, University Heidelberg, Mannheim, Germany, Neurosurgery, Johns Hopkins
University, Baltimore, MD, USA
Background and aims: It was recently suggested that altered sensory properties of peripheral
nociceptors underlie the UV-B-induced mechanical hypersensitivity. Using in vivo electrophysiology,
we investigated UV-B-evoked changes of mechanical and axonal properties of unmyelinated porcine
nociceptors.
Method: In 35 anesthetized male pigs, single-fiber extracellular recordings of saphenous nerve were
performed 10-24 hours after UV-B irradiation of its innervation territory (0.24 J/sqcm, ~25 squares
distributed in a chessboard pattern). Contralateral non-irradiated limbs served as control. Cnociceptors were classified based on sensory modality and activity-dependent slowing (ADS) of
conduction velocity. Receptive fields were mapped mechanically or electrically (for the mechanoinsensitive units). Axonal characterization comprised electrical thresholds, peak following frequency
and ADS. Mechanical sensitivity at both threshold and supra-threshold levels was tested by an
actuator-driven stimulator delivering half-sine-shaped mechanical forces of controlled duration and
amplitude. Ipsilaterally, irradiated and non-irradiated fields of single units were identified by collision
and the testing was done for each branch separately.
Results: The distribution of C-fiber classes was similar between irradiated (n=88) and control skin
(n=43). In UV-B hindlimbs, 29 units had receptive fields covering irradiated and non-irradiated areas.
Mechanical thresholds of C-nociceptors were dramatically lower in irradiated fields (medians: 6 vs.
0.5; n= 14) and paralleled by increased discharge upon supra-threshold mechanical stimulation.
Among mechano-insensitive C-afferents, lower ADS and increased peak following frequency were
recorded.
Conclusion: Reduced mechanical thresholds, increased supra-threshold encoding and axonal
sensitization of C-nociceptors can contribute to UV-B induced hyperalgesia.
Supported by: BMBF and DFG.
111
TAPENTADOL USE IN FIBROMYALGIA (FM): A PROSPECTIVE COHORT STUDY
F. Atzeni, R. Talotta, F. Rigamonti, A. Batticciotto, P. Sarzi-Puttini
Rheumatology Unit, L.Sacco University Hospital, Milan, Italy
Background and aim: To prospectively evaluate the efficacy and safety of tapentadol (TAP)
prolonged release in FM patients.
Methods: This study included 100 FM . Information regarding symptom and functional status was
recorded at baseline and at 1, 3,6 and 12 months after the baseline visit. FM patients who had VAS
pain scores ≥ 40 were treated with initial dose of TAP of 100 mg/day for a 3-month period. After week
2, the TAP dosage could be escalated to 200 mg/day as, by the end of the study up to 300 mg/day as
needed to treat symptoms effectively, and the dosage could also be decreased for tolerability. The
efficacy parameter was the percentage of patients rating themselves as "much or "very much
improved" on the PGIC at the 6-month. Other parameters included changes VAS pain, FIQ, and FAS
and the survival rate on TAP after 6 and 12 months of treatment.
Results: Of patients treated with TAP, 22 % were classified as PGIC responders at 6 month of
treatment, and they also demonstrated improvement in VAS pain, FIQ total, and FAS total scores
(mean changes from baseline were -16.5, -13.1, and -1,8). 52 % of patients interrupted the treatment
due to inefficacy or side-effects durng the 12-month study. 15% of the patients were treated
intermittently (at least 6-month of therapy). The most common treatment-emergent adverse events
(incidence ≥10%) were nausea, dizziness and headache.
Conclusions: Results from this exploratory study suggest that TAP may be beneficial in some
patients with FM.
112
CENTRAL SENSITIZATION IN FIBROMYALGIA AND CHRONIC LOW BACK PAIN: A
SYSTEMATIC REVIEW ON USING FUNCTIONAL AND STRUCTURAL BRAIN IMAGING
1
1
1
1
B. Cagnie , S. Denecker , J. Six , L. Danneels , M. Meeus
1
1,2
2
Department of Rehabilitation Sciences and Physiotherapy, Ghent University, Ghent, University of
Antwerp, Antwerp, Belgium
Background and aims: The aim of the present study was to systematically review the literature
addressing pain induced changes in the brain related to central sensitization in patients with
fibromyalgia (FM) or chronic low back pain (CLBP) using functional (functional magnetic resonance
imaging - fMRI) and structural (Voxel-Based Morphometry - VBM) medical imaging.
Methods: Pubmed en Web of Science were searched for relevant literature using different key word
combinations related to FM, CLBP, imaging en central sensitization. Full text reports fulfilling the
inclusion criteria were reviewed on methodological quality by two independent reviewers.
Results: From the 70 articles that were identified, 17 met the inclusion criteria and achieved sufficient
methodological quality. Five articles examined structural brain (VBM) changes in chronic pain
patients, showing moderate evidence that central sensitization is correlated with gray matter volume
decrease in specific brain regions (mainly anterior cingulate cortex and prefrontal cortex). Global gray
matter volume however remains unchanged. Twelve articles evaluated brain activity (fMRI) in
response to a nociceptive stimulus. Findings suggest a higher but similar pattern of activation of the
pain matrix in chronic pain patients compared to controls. There is also evidence of decreased
functional connectivity in the descending pain modulating system in FM patients.
Conclusions: The included studies showed a moderate evidence for region-specific changes in gray
matter volume, a decreased functional connectivity in the descending pain modulating system and an
increased activity in the pain matrix related to central sensitisation. More research is needed to
evaluate the cause-effect relationship.
113
PRESYNAPTIC GABAERGIC INHIBITION REGULATED BY BDNF CONTRIBUTES TO
NEUROPATHIC PAIN INDUCTION
1
1
1,2
3
2
J.T.-C. Chen , D. Guo , D. Campanelli , R. Kuner , M. Knipper , J. Hu
1
1
Werner Reichardt Centrum für Integrative Neurowissenschaften (CIN), University of Tübingen,
3
Hearing Research Centre, University of Tübingen, Tübingen, Pharmacology Institute, University of
Heidelberg, Heidelberg, Germany
2
Background and aim: The gate control theory pointed out the importance of both pre- and postsynaptic inhibition in controlling the pain signal processing in spinal cord. Loss of postsynaptic
inhibition caused by BDNF is a crucial mechanism underlying neuropathic pain. However, the function
of presynaptic inhibition in pain behavior remains elusive. Here we propose that BDNF binding to
presynaptic TrkB receptors on primary afferents may regulate the presynaptic inhibition via control of
presynaptic GABAA receptor function after nerve injury and therefore contribute to neuropathic pain.
Methods and results: By performing gramicidin-perforated patch clamp, we observed a transient
depolarizing shift in the reversal potential (EGABA) and a reduction in the conductance of presynaptic
GABAAR in DRG neurons after CCI, both leading to a reduction of presynaptic inhibition. Specifically,
-/knocking out of the GABAAR in primary nociceptors (sns-β3 ) could prevent the pain symptoms that
developed after nerve injury. Exogenous BDNF mimicked the alteration in both GABAAR function and
the neuropathic pain syndrome, whereas blocking BDNF and its receptor TrkB signaling reversed the
change of GABAAR function after nerve injury. Finally, intrathecal injection of BDNF failed to induce
neuropathic-pain like behavior in nociceptor-specific GABAAR knockout mice.
Conclusion: Our results suggest that BDNF not only produces an excitatory shift of postsynaptic
inhibition, but also temporally abolishes presynaptic GABAergic inhibition after nerve injury and leads
to the generation of neuropathic pain. Our findings reveal a novel effect of BDNF on presynaptic
GABAergic inhibition in neuropathic pain initiation.
114
LONG-LASTING HYPERALGESIA INDUCED BY SUBCUTANEOUS HIGH FREQUENCY
ELECTRICAL STIMULATION (SHFES) IS MEDIATED BY THE NEUROTROPHIN BDNF
1,2
1,2
1
3
1
L. Constandil , J. Retamal , D. Bravo , T. Pelissier , C. Laurido , A. Hernández
1
1
2
Laboratorio de Neurobiología, Universidad de Santiago de Chile, Chile, Center for Integrative
3
Medicine and Innovative Science, Universidad Andrés Bello, Programa de Farmacología Molecular y
Clínica, Universidad de Chile, Santiago, Chile
Various chronic pain models have been used to study plastic changes observed in chronic pain, but
all of them produce peripheral lesions thus masking processes involved at the beginning of such
changes.
We induce a long-lasting decrease in the nociceptive threshold of the rat hindpaw by using SHFES
and studied the participation of BDNF in the first stage of central sensitization. SHFES (eighteen
trains of 1 s duration each, composed by electric pulses of 120 V, 1 ms at 100 Hz) were given to the
right hind paw at zero time and repeated after 10 min under isoflurane anesthesia. SHFES neither
produced visible injury in the metatarsal surface nor change the locomotor pattern.
Results showed that stimulated animals had a significant 30% decrease in nociceptive threshold
(Randal Sellito) 1 h post-stimulation, which remained decreased until day 21. Cyclotraxin B
(antagonist of TrkB receptor) injected 3 day before or 3 day after the SHFES prevented and reverted
the effect of SHFES, respectively. Pre-stimulation BDNF level (ELISA) in the spinal cord (22.33 ± 0.6
pg / mg protein) increased 6 hours post-stimulation (30.91 ± 1.35 pg BDNF/mg protein ) but after 24
hours the level was found to be decreased (10.53 ± 0.57 pg/mg protein), an effect that persisted until
day 7. The pTrkB level (ELISA) followed a similar pattern. Results show that SHFES applied to toes
produce long-lasting hyperalgesia in the hindlimb of the rat and that BDNF plays an important role in
the beginning on this process. FONDECYT Nº1120952.
115
PERIPHERAL AND CENTRAL SENSITIZATION IN PEOPLE WITH OSTEOARTHRITIS OF THE
KNEE: A SYSTEMATIC REVIEW
1
2
1
C. Fingleton , K. Smart , C. Doody
1
2
School of Public Health, Physiotherapy and Population Science, University College Dublin, St.
Vincent's University Hospital, Dublin, Ireland
Background and aims: It has been suggested that changes in central pain processing play an
important role in pain associated with Osteoarthritis (OA) of the knee. A systematic review was carried
out according to the PRISMA guidelines to evaluate the evidence for peripheral and central
sensitization in people with OA of the knee.
Methods: A search was carried out of the databases Pubmed, Web of Science, Embase, Cinahl and
Cochrane combining Knee OA with pre-defined keywords relevant to pain sensitization. All full text
clinical reports and all study designs studying peripheral and central pain sensitization in humans > 18
years were eligible for inclusion.
Results: Following screening of 537 titles, 49 abstracts were identified by 2 reviewers. Twelve full text
articles which met the inclusion criteria were included in the final review. The studies evaluated
patients' responses to a variety of mechanical, thermal and electrical stimuli in addition to patient
reported measures of pain and function. Findings suggestive of peripheral and central sensitization
included local and diffuse hyperalgesia, most notably significantly decreased pressure pain
thresholds, tactile hypoaesthesia, increased temporal summation, heightened flexor withdrawal
responses, and neuropathic pain classified using painDETECT.
Conclusions: Generalised hyperalgesia to different stimuli at local and remote sites are suggestive of
the presence of central sensitization processes in subgroups of people with OA of the knee. Future
research is necessary to further understand the underlying neurophysiological pain mechanisms in
addition to the clinical implications of assessment and treatment of central sensitization.
116
N2O DOSE-DEPENDENTLY REDUCES REMIFENTANIL INDUCED HYPERALGESIA IN HUMAN
VOLUNTEER
1
1
2
2
2
2
J. Henning , A.P. Wehrfritz , B. Bessière , J. Hazebroucq , S. Khairallah , N. Noel
1
Dept of Anaesthesiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany,
Air Liquide Santé International, Jouy-en-Josas, France
2
Background: Opioids remain the cornerstone therapy to reduce perioperative pain. Nevertheless
those drugs induce, after their analgesic effect, the activation of NMDA-receptors which cause a
significant raise of hyperalgesia, allodynia and pain. A former study showed that inhalation of 50%50% nitrous oxide (N2O)-oxygen mixture limits those undesirable effects. The dose-effect relationship
between N2O 35% and 50% was evaluated in this study.
Methods: After IRB approval, 21 volunteers were randomly assigned to 4 sessions. Continuous pain
was generated by intra-cutaneous electrical stimulation (CCES-Model). Each subject underwent the
following sessions: Placebo(A): 50%-50% N2-O2 and i.v. saline; Remifentanil(B): 50%-50% N2-O2
and i.v. remifentanil; 35%-N2O(C): 35%-15%-50% N2O-N2-O2 and i.v. remifentanil; 50%-N2O(D):
50%-50% N2O-O2 and i.v. remifentanil. The administration of gas mixtures, i.v. Remifentanil (0.1
µg/kg/min) or saline started 20 minutes after the beginning of the electrical stimulation. I.v.
administrations lasted 30 min., gas inhalation lasted 60 min. Areas of hyperalgesia and allodynia
around the electrodes and pain intensity were evaluated regularly during 160 minutes.
Results: Area of hyperalgesia, post-treatment, in remifentanil session was observed (difference B vs.
2
A +6.3 ± 1.7cm , p=0.0012). N2O 35%+Remifentanil (C) and N2O 50%+Remifentanil (D) reduced the
hyperalgesia, allodynia and pain compared to remifentanil (B) (significant differences vs. B for relative
changes from baseline(%), p< 0.002). Besides, significant differences were observed between N2O
35% and 50% for relative changes (%) of hyperalgesia, (-13.9 ± 2.7%, p< 0.0001), allodynia (-9.1 ±
2.8%, p= 0.0059) and pain intensity (-5.0 ± 1.0%, p< 0.0001).
Conclusions: N2O dose-dependently reduces Remifentanil induced hyperalgesia and allodynia.
117
PREDICTING TRANSITION FROM ACUTE TO CHRONIC LOW BACK PAIN WITH QST PRELEMINARY RESULTS OF A POPULATION BASED COHORT
1,2
1
1
3
3
2
M. Müller , A. Neziri , C. Oehler , O.K. Andersen , L. Arendt-Nielsen , P. Jüni , M. Curatolo
1
1
2
University Clinic of Anesthesiology and Pain Medicine, Inselspital, Institute of Social and Preventive
3
Medicine, University of Bern, Bern, Switzerland, Center for Sensory-Motor Interaction, University of
Aalborg, Aalborg, Denmark
Background and aim: Some predictors of the transition from acute to chronic low back pain have
been identified, but they explain the phenomenon only to a limited extent. Alterations in central pain
processing may occur in the acute phase and could represent a predicting factor for the development
of chronic pain. Our primary objective was to determine the prognostic value of central
hypersensitivity assessed using quantitative sensory tests in patients with acute low back pain for
developing chronic pain.
Methods: Patients for this prospective cohort study are recruited in a primary care practice. We
computed unadjusted and adjusted logistic regression models to assess the effect of central
hypersensitivity on persistent low back pain after six months. Central hypersensitivity was defined
based on published normative values of QST.
Results: We report preliminary results of 41 patients. 44% were females. Mean age and NRS at
baseline were 41.0 (SD 12.5) and 4.8 (SD 1.5). 15% suffered from depression (Beck Depression
Inventory) and 10% from anxiety (STAI) at baseline. Unadjusted OR (95%CI) for pressure pain
detection threshold, our primary prognostic variable, was 3.8 (0.8; 18.3) p=0.094. After adjustment for
gender, depression, anxiety, age and NRS at baseline, it increased to 5.9 (1.0; 35.8), p=0.056. Heat
and cold pain thresholds showed the same trend.
Conclusion: Although limited by a small sample size with consequently lacking power, our
preliminary results suggest that central hypersensitivity may be associated with chronic back pain six
months after the acute phase.
118
CONDITIONED PAIN MODULATION IN CHRONIC LOW BACK PAIN PATIENTS
N.T. Oliveira, J.B. Corrêa, R.E. Liebano
Master's and Doctoral Programs in Physical Therapy, Universidade de São Paulo (UNICID), São
Paulo, Brazil
Background and aims: Inefficient endogenous pain control and central sensitivity are important
characteristics in patients with low back pain. Prolonged afferent nociceptive impulses may lead to
increased excitability of the central sensory neurons and changes in their plasticity that lead to
hypersensitivity resulting in an exaggerated response to pain. Central sensitization has been shown
as an underlying mechanism of pain in low back pain and for chronic musculoskeletal pain in general.
The aim of this study was to investigate the integrity of analgesic descending pathways in patients
with chronic low back pain.
Methods: We compared 30 patients with chronic low back pain with 30 matched healthy controls. A
cold pressor test was used to assess the activation of the conditioned pain modulation (CPM). The
pressure pain threshold (PPT) at the low-back algometry points were recorded 30 seconds after
o
immersion of patient's foot in a bucket with cold water (4 C). PPTs were measured from the lumbar
region (bilaterally in 5 cm lateral to the L3 spinous process and 5 cm lateral to the L5 spinous
process).
Results: Patients with chronic low back pain have significantly lower PPT than controls in lumbar
region (p=0.001) during CPM test.
Conclusions: Patients with chronic low back pain presented impaired endogenous pain control. The
data suggest the inhibition of endogenous pain control to be a potential mechanism underlying pain in
low back pain and hence targets for pain management strategies.
The authors thank from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP),
Brazil.
119
THE NEUROPATHIC CHARACTERISTICS OF OSTEOARTHRITIS KNEE PAIN IN SPAIN. THE
ENDARE STUDY
1
2
3
4
I. Sanchez-Magro , A. Oteo-Alvaro , M.A. Ruiz-Iban , X. Mingues Vazquez , J. Villoria
1
5
2
Medical Department Grünenthal Iberia, Department of Orthopaedic Surgery and Traumatology,
3
Gregorio Marañón University General Hospital, Department of Traumatology and Orthopaedic
4
Surgery, Ramón y Cajal University Hospital, Madrid, Rehabilitation Service, Monforte Hospital, Lugo,
5
Department of Design and Medical Writing, Medicxact, Madrid, Spain
Rationale: The appearance of neuropathic pain (NP) could partially explain the relationship between
the level of change in the tissue, and the intensity and quality of pain symptoms in knee osteoarthritis
is limited.
Objective: To estimate the prevalence of neuropathic characteristics in osteoarthritis knee pain and
to assess how it interacts with several factors.
Material and methods: A nationwide, cross-sectional study using socio-demographic and clinical
data, as well as two knee pathology elements from BPI and DN4.
Results: Data on 2992 knees from 2167 patients out of a total of 2776 recruited patients was
analysed. The DN4 score was ≥4 in 1459 knees (48.8%) from 1125 patients (51.9%). These figures
dropped to 29.4% and 33.3% respectively, after exclusion of patients with non-osteoarthritis
conditions that could affect the innervation of the knee (innervation factors). Patients with possible DN
(DN4 ≥4) show reduced mobility, lower radiological grading, a higher number of innervation factors
and unfavourable constitutional factors, and greater pain intensity. The increased variability in the
DN4 score is explained by three innervation factors (other conditions that cause abnormal sensations,
or changes in sensitivity of the knee area, or pain irradiating from the knee to the back or hip).
However, latent class analysis suggested that DN4 may even detect more patients that do not present
the aforementioned factors.
Conclusion: A significant proportion of patients with chronic osteoarthritis knee pain may have a
possible neuropathic component.
120
RESULTS OF SWITCHING TO TAPENTADOL IN FIBROMYALGIA PATIENTS WITH AN
INADEQUATE RESPONSE TO DULOXETINE: A PILOT STUDY
P. Sarzi-Puttini, A. Batticciotto, R. Talotta, F. Atzeni
Rheumatology Unit, L.Sacco University Hospital, Milan, Italy
Background and aim: To evaluate the safety, tolerability, and efficacy of tapentadol (TAP) prolonged
release following a direct switch from duloxetine in fibromyalgia (FM) patients experiencing
inadequate clinical response to duloxetine (DL).
Methods: The study included 50 patients with FM who had been treated with DL 60 mg/day for at
least 4 weeks prior to enrollment. Following a 4-week open-label period on DL, patients who had VAS
pains ≥ 40 and were dissatisfied with current treatment were treated with initial dose of TAP of 100
mg/day for a 3-months. After week 2, the TAP dosage could be escalated to 200 mg/day as, by the
end of the study up to 300 mg/day as needed to treat symptoms effectively, the dosage could also be
decreased for tolerability. The primary efficacy parameter was the percentage of patients rating
themselves as "much or very much improved" on the Patient Global Impression of Change (PGIC) at
the 3-month visit. Other parameters included changes VAS pain, FIQ, and FAS.
Results: Of patients switched to TAP, 26 % were classified as PGIC responders, and they also
demonstrated improvement in VAS pain, FIQ total, and FAS total scores (mean changes from
baseline were -18.5, -14.3, and -2.1) after 3 months of treatment. 36% of the patients interrupted the
treatment due to the adverse events. Nausea and dizziness were the most common.
Conclusion: This study suggests that switching from DL to TAP may be beneficial in some patients
with FM who have an inadequate response to DL.
121
A RANDOMIZED TRIAL EVALUATING THE EFFECTS OF 35% AND 50% N2O ON
REMIFENTANIL INDUCED HYPERAESTHESIA AND PAIN IN HUMAN VOLUNTEER
1
1
2
2
2
2
A.P. Wehrfritz , J. Henning , B. Bessière , J. Hazebroucq , S. Khairallah , N. Noel
1
Dept of Anaesthesiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany,
Air Liquide Santé International, Jouy-en-Josas, France
2
Background: Reduction of perioperative pain includes the administration of opioids. Those drugs
activate NMDA-receptors which could cause a significant raise of hyperaesthesia and pain. A former
study showed that 50%-50% nitrous oxide (N2O)-oxygen mixture is able to suppress those
undesirable effects. This study was conducted to evaluate the impact of 35% N2O.
Methods: After IRB approval, 21 volunteers were randomly assigned to 4 sessions. Continuous pain
was generated by intra-cutaneous electrical stimulation (CCES-Model). Each subject underwent the
following sessions: Placebo(A): 50%-50% N2-O2 and i.v. isotonic saline; Remifentanil(B): 50%-50%
N2-O2 and i.v. remifentanil; 35%-N2O(C): 35%-15%-50% N2O-N2-O2 and i.v. remifentanil; 50%N2O(D): 50%-50% N2O-O2 and i.v. remifentanil. Both administration of gas mixtures and i.v.
substrates (0.1 µg/kg/min.) started at T20. I.v. lasted for 30min., gas inhalation for 60min.
Hyperalgesia, allodynia and pain intensity were evaluated regularly during 160 minutes.
Results: Area of hyperalgesia, post-treatment, in remifentanil session was observed (difference B vs.
A +6.3 ± 1.7cm2, p=0.0012). Relative change from baseline(%) of areas of hyperalgesia, allodynia
and pain intensity were significantly reduced in N2O+ Remifentanil sessions (C and D) as compared
to Remifentanil session (B) (-44.4 ± 2.5% (C) and -58.3 ± 2.5% (D) vs. 18.1 ± 2.5% (B) for
hyperalgesia (p< 0.0001), and -42.8 ± 3.0% (C) and -51.9 ± 3.0% (D) vs. 3.8 ± 3.0% (B) for allodynia
(p< 0.0001), and -24.5 ± 2.7 % (C) and -29.5 ± 2.7% (D) vs.-20.1 ± 2.7% (B) for pain (p≤ 0.0002)).
Conclusions: N2O 35% and 50% reduced remifentanil induced hyperalgesia, allodynia and pain.
122
PAIN INHIBITON AFTER EXPERIMENTAL SLEEP DEPRIVATION IS GENDER DEPENDENT
1,2
M.R. Andersen , K.B. Nilsen
1,3,4
1
, J.T. Stuenæs , D. Matre
1
1
Dept of Work Psychology and Physiology, National Institute of Occupational Health, Oslo,
3
Norwegian University of Life Sciences, Ås, Department of Neurology, Section for Clinical
4
Neurophysiology, Oslo University Hospital, Department of Neuroscience, Norwegian University of
Science of Technology, Oslo, Norway
2
Background and aims: Reduced sleep quality and quantity has been shown to enhance pain
perception and pain sensitivity. This has been linked to altered function in the pain modulatory
pathways. The aims of this study were
1) to determine if sleep restriction leads to altered pain inhibition, and
2) to determine if there are gender differences.
Method: In a cross-over design with two conditions (2 nights normal sleep vs. 2 nights 50 % sleep)
the pain inhibitory system was tested in 22 healthy individuals (14 female) with the conditioned pain
modulation (CPM) paradigm. Test stimulus (TS) was 2-min contact heat (TS), conditioning stimulus
(CS) was 7 degC cold water (CS). TS was given 'before CS' and 'during CS'.
Results: TS pain inhibition was stronger following deprived vs. following normal sleep (p < 0.001).
This difference was driven by the women, whose TS pain ratings were higher 'before CS' following
deprived sleep vs. following normal sleep (p < 0.001). Among men, TS pain ratings and TS pain
inhibition were not different between the two sleep conditions (p > 0.272).
Conclusions: The results indicate that in men, the pain inhibitory system is not affected by sleep
deprivation. In women, the results indicate a stronger pain inhibitory effect after sleep deprivation.
Whether this effect is driven by a stronger pain inhibitory effect after sleep deprivation or by a higher
rating of TS pain after sleep deprivation needs further investigation.
123
PAIN SENSITIVITY AND POTENCY OF CONDITIONED PAIN MODULATION: IS THERE ANY
RELATIONSHIP? - A HEALTHY HUMAN STUDY
1
2
2
1
Z. Zheng , K. Wang , D. Yao , C.C.L. Xue , L. Arendt-Nielsen
1
2
2
School of Health Sciences, RMIT University, Bundoora, VIC, Australia, Center for Sensory-Motor
Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg
University, Aalborg, Denmark
Background and aims: To investigate the relationship between pain sensitivity and potency of
conditioned pain modulation (CPM).
Methods: Forty-one healthy volunteers (M:F=20:21, age 27±6) received conditioning stimulation (CS)
o
over two sessions in a random order: tonic heat pain (46 C) on the right leg for 7 minutes and cold
o
pressor pain (1-4 C) to the left hand for 5 minutes. Participants rated the intensity of pain continuously
using a 0-10 electronic visual analogues scale (VAS). As outcome measures pressure pain thresholds
(PPT) were measured at the bilateral extensor carpi radialis and right soleus before, during and 20
minutes after CS. Pearson correlations and t-tests were applied for data analyses.
Results: A difference between ratings of peak pain to cold CS and pain at the end of stimulation
(VASP-E) over 2 out 10 on VAS was used as a cutoff point to classify individuals who were pain
tolerant (n=16) or pain sensitive (n=25). Pain tolerant individuals required one third less time to reach
peak pain, reported one-third less pain at the end of CS, and had higher PPT increases at the CS
sites. The two groups did not differ on age, gender, and severity of the peak pain. VASP-E was
positively correlated with PPT increases at the stimulation site 20 minutes after CS (heat: r=0.36, p<
0.05; cold: r=0.37, p< 0.05), but not PPT changes related to CPM.
Conclusions: Pain sensitivity is not correlated with potency of CPM. Pain tolerant individuals
displayed fast-acting pain facilitation, and strong segmental pain inhibition.
124
RELIABILITY OF THE CONDITIONED PAIN MODULATION TEST PARADIGM FOR THE
ASSESSEMENT OF ENDOGENOUS PAIN INHIBITION
1
1
2
T. Bossmann , T. Brauner , H. Lowak , T. Horstmann
1
1,3
2
Conservative and Rehabilitative Orthopaedics, Technische Universität München, Physical Therapy
3
Practice Rothschwaige, Munich, Medical Park Bad Wiessee, Klinik St. Hubertus, Bad Wiessee,
Germany
Background and aims: Conditioned pain modulation (CPM) test paradigms have become
increasingly popular for quantifying the effectiveness of descending pain inhibition. Within these test
paradigms, interdigital web pinching (IWP) has been shown to be a valid conditioning stimulus.
However, reliability of this method has not been examined yet. The aim of this study was to examine
interrater reliability and standard error of measurement of the CPM test paradigm using interdigital
web pinching as a model for the assessment of endogenous pain inhibitory pathways.
Methods: Twenty healthy subjects (m:9, f:11, age: 34±10yrs) were examined on two days by different
testers respectively. Pressure pain threshold (Wagner Pain Test FPN 100), measured at the thenar of
the dominant hand, served as the test stimulus before and after a two minute period of IWPstimulation. Interdigital web pinching was applied between index and middle finger of the nondominant hand. The intensity was adjusted until a pain intensity of VAS 6 (of 10) was reached. The
pre-post difference in pressure pain threshold was analyzed: positive values indicated an effective
pain inhibition. Intraclass-correlation-coefficient and standard error of measurement were calculated.
Results: There were no significant differences between testers (mean increase of pressure pain
threshold after IWP stimulation: 4,55+/-2,37N and 4,13+/-4,25N). Intraclass-correlation-coefficient:
0,76 (p=0,002 95%CI: 0,39-0,91). Standard error of measurement: 1,62N.
Conclusions: The results showed that our CPM test paradigm is able to quantify endogenous pain
inhibitory pathways in healthy pain-free subjects. Reliability of our test procedure is high and there is
no substantial measurement error.
125
TONIC PAIN-LIKE AND EMOTIONAL BEHAVIORS IN PRENATALLY STRESSED RAT PUPS OF
DIFFERENT AGES, STRESS-COPING STRATEGIES
I. Butkevich, V. Mikhailenko
I.P.Pavlov Institute of Physiology Russ Acad Sci, Saint Petersburg, Russia
Background and aims: Tonic pain-like and emotional behaviors were studied in prenatally stressed
rat pups of different ages and stress-coping strategies were evaluated.
Methods: Rat dams were exposed to restraint stress during the last week of pregnancy (controls,
undisturbed dams). In 7-8, 10-11, and 14-15-day-old male offspring, formalin-induced pain was
examined before and 24 hours after emotional/physical stress (the forced swimming). In other rat
pups from the same litters, psychoemotional behavior in the forced swim test was examined before
and 24 hours after painful stress (the formalin test). Coping strategies to stress stimuli were evaluated
depending on ages.
Results: Prenatally stressed animals revealed strengthening of pain depending on age. Forced
swimming cancelled significant differences in the time-course of formalin-induced pain between
prenatally stressed pups and controls in the first and second age groups. Comparative analysis of the
pain time-courses before and after postnatal stress indicated a decrease formalin-induced pain during
the tonic phase in prenatally stressed 10-day-old pups. Prenatal stress increased the time of
immobility only in 7-8-day-old pups, and failed to change in 10-11- and 14-15-day-olds. Painful stress
decreased this index in pups of all age groups, but did not changed in controls.
Conclusions: Control pups display resistance to the stress stimuli. In prenatally stressed animals,
coping strategy of tonic pain behavior to stress shows itself in antinociception in 10-11-day-old rat
pups, whereas the emotional behavior in response to painful stress demonstrates high coping
strategy regardless of age.
Acknowledgement: This work was supported by the RFBR (N 11-04-01381-а).
126
LLINKING HARM AVOIDANCE AND INHIBITORY PAIN MODULATION
1
1,2
1
1
H. Nahman-Averbuch , D. Yarnitsky , Y. Granovsky , E. Sprecher , M. Granot
1
2
3
3
Technion - Israel Institute of Technology, Rambam Medical Center, University of Haifa, Haifa, Israel
Background and aims: Cloninger´s tridimensional personality theory includes harm avoidance (HA),
novelty seeking (NS) and reward dependence (RD) traits that relate to particular neurotransmitters of
serotonin, dopamine and noradrenalin. The scores of these traits were associated with experimental
pain perception obtained by the static psychophysical measurements (pain thresholds and pain
ratings). We hypothesized that personality traits representing these particular neurotransmitters are
involved in the expression of EA capacity. This study aimed to explore whether excitatory and
inhibitory pain modulation responses revealed by CPM and temporal summation paradigms, are
associated with personality traits obtained by the Tridimensional Personality Questionnaire (TPQ).
Methods: Healthy middle-age subjects (n=33), completed the TPQ and were assessed for CPM
responses. We used thermal phasic temporal summation for ´test-stimulus´ and hand immersion into
hot water bath (CPMwater) or contact heat (CPMcontact) for ´conditioning-stimulus´.
Results: Higher levels of HA were associated with less efficient CPM responses obtained for both
paradigms: CPMwater (r=0.374, p=0.050) and CPMcontact (r=0.418, p=0.027). However, HA, NS and
RD were not associated with any of the static psychophysical assessed measurements.
Conclusions: The lower capacity of pain inhibition which characterized individuals with greater
tendency to avoid aversive experience can be explained by mutual mechanisms involving modulation
processes invoked by nociceptive input and behavioral features of pain perception. These findings
illuminate the key role of pain related personality factors in determining the characteristics of pain
modulation profile. Therefore, an assessment of CPM should encompass evaluation of the personality
traits mainly via tools that represent bio-psychosocial facets of pain.
127
EXERCISE-INDUCED HYPOALGESIA AND CONDITIONED PAIN MODULATION IS NOT
CORRELATED WITH STATUS OF PHYSICAL ACTIVITY
1
1
2
2
H.B. Madsen , G. Handberg , M. Jørgensen , A. Kinly , T. Graven-Nielsen
1
3
2
Pain Center South, University Hospital Odense, Odense C, The Institute of Sports Science and
3
Clinical Biomechanics, Faculty of Health Sciences, University of Southern Denmark, Odense, Center
for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of
Medicine, Aalborg University, Aalborg, Denmark
Background and aim: Pain modulation is often assessed by paradigms of exercise and experimental
pain. The aim of this study was to investigate whether exercise-induced hypoalgesia (EIH) and
conditioned pain modulation (CPM) differed between active and non-active subjects.
Methods: Fifty-six healthy subjects (28 females) with a mean age of 22.8±2.1 years performed a
bicycling exercise (15 minutes at 75% VO2 max), a cold pressor test for the dominant hand (stirred
ice water at 1-2ºC; 120 seconds duration), and a 15 minutes rest condition in randomized,
counterbalanced order. Pressure pain threshold (PPT) and pressure pain tolerance (PTT) was
assessed on the non-dominant leg and arm before, immediately after, and 15 minutes after each
condition. Subjects were sub-grouped into active and non-active groups based on the
recommendations on physical activity by the Danish Health and Medicines Authority. Repeated
measures ANOVAs and multiple comparisons were used for analysis.
Results: Active subjects had significantly higher PTT at baseline compared with non-active subjects
(P< 0.05). In both active and non-active subjects the PPTs and PTTs were significantly increased
immediately after exercise and cold pressor test compared to baseline and rest (P< 0.05) but the
relative increase was comparable in both groups.
Conclusions: Pressure pain tolerance was increased in active subjects compared to non-active
subjects. Exercise and cold pressor test produced significant EIH/CPM but the effects were not
significantly related to physical activity behaviour or gender in this study.
Acknowledgement: HBM was supported by grants from the philanthropic foundation TrygFonden (711-0990).
128
INFLAMMATORY PAIN AND HYPORESPONSIVE PERIOD OF THE HPA AXIS IN RAT PUPS
WITH DIFFERENT PRENATAL TREATMENTS
V. Mikhailenko, I. Butkevich, T. Bagaeva
I.P.Pavlov Institute of Physiology Russ Acad Sci, Saint Petersburg, Russia
Background and aims: Prenatal stress induces exacerbation of inflammatory pain and increases
activity of the hypothalamo-pituitary-adrenal (HPA) axis. 5-HT1A receptors are involved in these
processes. The work addresses interrelations between these systems in early ontogeny. The aim of
the study was to investigate the temporal dynamics of inflammatory pain-like and stress
corticosterone responses in the formalin test during the HPA axis hyporesponsive period in rats with
different prenatal treatments.
Methods: Male rats at the age of 7, 10 and 14 days born to dams treated with buspirone or saline
th
(from the 9 day of pregnancy) and to buspirone+stress or saline+stress (during the last week of
pregnancy) were used in the study. Flexes/shakes patterns were recorded in the formalin test. Blood
samples were collected by decapitation during the acute, tonic phases and the interphase in the
formalin test and 24 hours after it. Plasma corticosterone levels were determined by microfluorometry.
Results: Prenatal stress increased pain reaction in the formalin test. Prenatal injections of buspirone
prior to stress normalized pain-like behavior. Formalin-induced pain increased plasma corticosterone
level in the animals. Age differences in the temporal dynamics of the tonic nociceptive reaction and of
stress corticosterone value in response to inflammatory pain were revealed.
Conclusions: The data enhance the idea about relatività of the HPA axis hyporeactive period and
testify that 5-HT1A activation prior to prenatal stress increases adaptation of the tonic nociceptive
system and enhances stress corticosterone responses in accordance with age.
Acknowledgement: This work was supported by grant RFBR 11-04-01381-а.
129
CONDITIONED PAIN MODULATION IN TEMPOROMANDIBULAR DISORDERS PATIENTS
1,2
1,3
4
4
2
2
2
Y. Oono , K. Wang , L. Baad-Hansen , S. Futarmal , S. Ogami , K. Matsumoto , H. Fukayama , H.
2
4,5
1
Kohase , P. Svensson , L. Arendt-Nielsen
1
Department of Health Science and Technology, Center for Sensory-Motor Interaction (SMI), Aalborg
2
University, Aalborg, Denmark, Section of Anesthesiology and Clinical Physiology, Department of Oral
3
Restitution, Tokyo Medical and Dental University, Tokyo, Japan, Department of Oral & Maxillofacial
4
Surgery, Aalborg Hospital, Aalborg, Section of Clinical Oral Physiology, Department of Dentistry,
5
Aarhus University, Center of Functionally Integrative Neuroscience (CFIN), MindLab, Aarhus
University Hospital, Aarhus, Denmark
Background and aims: Impairments of endogenous pain-modulatory pathways are implicated in
craniofacial pain conditions. The aims were to investigate 1) if temporomandibular disorders patients
with temporomandibular joint (TMJ) pain have different conditioned pain modulation (CPM) compared
with healthy subjects and, 2) if the clinical pain characteristics influenced CPM.
Methods: Twenty-four TMJ pain patients and 24 age-matched healthy volunteers participated.
Mechanical conditioning stimulus (CS) was applied to pericranial muscles by a headband provoking a
pain intensity of VAS=5/10. As test stimuli, pressure pain (PPT) and pressure pain tolerance
thresholds (PPTol) were applied to the painful TMJ, masseter, and forearm before, during, 20 min
after CS. Data were analyzed with ANOVAs. The correlations between CPM effect and TMJ pain
intensity or the duration (correlation coefficient; R) were calculated.
Results: The relative PPT and PPTol values (mean for three sites) during CS was significantly higher
than baseline in healthy subjects (35.2±15.9%, 26.5±18.3%; P< 0.001, P< 0.001) but not in the
patients (3.9±12.3%, -0.4±14.4%; P=0.824, P=1.000) (PPT and PPTol, respectively) with significant
differences between groups (P< 0.001). In patients, the relative PPT values during CS were not
significantly higher than baseline at TMJ (6.8±5.8%, P=0.915) and masseter (-8.4±5.0%, P=0.658) but
significantly higher at forearm (13.4±5.0%, P=0.023). A negative correlation was detected between
the TMJ pain intensity and CPM effect (R=-0.204) alike between the pain duration and CPM effect
(R=-0.228) at painful TMJ.
Conclusions: CPM is impaired in TMJ pain patients and the clinical pain intensity and duration are
important for the degree of impairment.
130
INTRA-ARTICULAR NERVE GROWTH FACTOR ENHANCES NOCICEPTIVE RESPONSES IN A
RAT MODEL OF OSTEOARTHRITIC PAIN
D.R. Sagar, D.A. Walsh, V. Chapman
Arthritis UK Pain Centre, University of Nottingham, Nottingham, UK
Background and aims: Increased expression of Nerve Growth Factorβ (NGFβ) in the joints of
osteoarthritis (OA) patients and the significant correlation between levels of NGFβ and pain behaviour
in a model of OA support a role of NGF in the pathophysiology of OA. The aim of the present study
was to investigate the effects of intra-articular injection of NGF on neuronal excitability in the
monosodium iodoacetate (MIA) model of OA.
Methods: Male Sprague Dawley rats (160-190g) received intra-articular injection of MIA (1mg/50µl)
or saline. Pain behaviour was assessed up to 21 days post-injection, following which rats were
anaesthetised and responses of single wide dynamic range spinal dorsal horn neurones ipsilateral to
injury were quantified. Movement-evoked responses, 26g-evoked receptive field size and neuronal
responses of the ipsilateral knee-joint were characterised. Rats received an ipsilateral intra-articular
injection of NGFβ or vehicle and movement-evoked responses, 26g-evoked receptive field size and
neuronal responses were measured for up to 2h post-drug administration.
Results: Intra-articular injection of MIA produced a characteristic weight bearing asymmetry,
compared to saline-treated rats. Intra-articular injection of NGFβ facilitated spinal neuronal responses
to movement, noxious mechanical stimulation of the knee-joint and produced a significant expansion
of peripheral receptive fields over the knee-joint in saline-treated rats. These effects of NGFβ on
neuronal responses were further increased in MIA-treated rats.
Conclusions: Facilitated responses of spinal neurones in MIA-treated rats were further increased by
intra-articular injection of NGFβ. These studies provide new evidence for the mechanisms by which
NGFβ contributes to OA pain.
131
ENDOGENOUS ANALGESIA EFFICIENCY BEFORE ORTHOPAEDIC SURGERY. CAN WE
PREDICT PERSISTENT POST-SURGICAL PAIN WITH PREOPERATIVE SENSORY TESTING?
1
1
1
1
2
Y. Salazar , U. Rodriguez , C. Dürsteler , A. Montes , L. Puig , F. Escolano
1
1
Dept of Anaesthesiology & Pain Medicine, Hospital del Mar. Universitat Autònoma de Barcelona,
Dept of Orthopaedic Surgery, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona,
Spain
2
Background; Goal of study: Incidence of persistent post-surgical pain (PPP) after orthopaedic
surgery is inadequately estimated. Preoperative endogenous analgesia (EA) efficiency has been
proposed as a valid tool to predict PPP. Our hypothesis suggests that patients with a preoperative
incompetent EA are more prone to develop PPP.We are conducting a study aimed to establish the
relationship between the preoperative efficiency of EA and persistent post surgical pain (PPP) after
total knee arthroplasty (TKA). We show the descriptive preliminary data.
Materials and methods: Prospective observational study in patients older than 18, scheduled for
TKA. EA efficiency was measured during the month previous to surgery using quantitative sensory
testing (QST). Variables: primary variable: 1. Presence of pain > 3 (VAS score; movement) in the
operated knee, 3 months after surgery. Secondary variables: 2. Preoperative EA efficiency measured
with QST. 3. Presence of preoperative generalised hyperalgesia.
Results and discussion: Mean age of patients was 72 years old, 69.6% of them female. The
incidence of PPP at 3 months was 64.3%. 40.7% of patients showed a preoperative inefficient EA,
and 42.9% generalised hyperalgesia. 71.4% of patients with preoperative anxiety showed generalised
hyperalgesia, present only in 34.1% of not anxious patients (p < 0.02).
Conclusion(s): Our preliminary data show a PPP incidence after orthopaedic surgery (TKA) similar to
that of other better-studied surgeries. An inefficient preoperative EA was present in 40.7% of patients,
probably at risk to develop PPP. Its predictive value will be established at the end of the study.
Supported by: ISCIIIGrant PI12/01422
132
THE EFFECTS OF PROGESTERONE ON LONG-TERM ALTERATIONS IN PAIN PERCEPTION
CAUSED BY NEONATAL INJURY
1
2
2
M. Soens , C.-F. Wang , G. Strichartz
1
2
Anesthesiology, Perioperative and Pain Medicine, Pain Research Center, Harvard Medical School Brigham and Women's Hospital, Boston, MA, USA
Introduction: Exposure to a noxious insult in early life alters CNS development and influences future
pain responses. Fetuses are exposed to high concentrations of progesterone. Progesterone has been
shown to modulate nociceptive processing. We hypothesized that progesterone protects the
fetus/neonate from alterations within the developing nervous system in response to a noxious
stimulus, and that this modulation acts through spinal mitogen activated protein kinases (MAPKs).
Methods: After birth, rat pups were assigned to 4 groups:
Group 1 (n=6): progesterone (twice daily) P1-P7 (P=postpartum day) + P3 incision hindpaw +
repeat paw incision P60.
Group 2 (n=6): vehicle injections P1-7 + P3 and P60 paw incision
Group 3 (n=5): no injections + P3 and P60 paw incision
Group 4 (n=5): no injections + paw incision P60 only.
Beginning at P14, thermal paw withdrawal latencies and mechanical thresholds were determined.
On P67, spinal cords were harvested and activation of the spinal MAP kinase p38 determined (n=2
per group).
Results:
1) Behavioral:
[Hargreaves Paw Withdrawal Latencies]
[Von Frey Mechanical Thresholds]
6
2
2) Immunohistochemistry: p-p38 positive cells per 10 Pixel :
Group 1: 33.5 ± 2.1;
Group 2: 64.4 ± 4.7;
Group 3: 50.1 ± 1.8;
Group 4: 40.3 ± 1.3. (group 2 vs group 4: p< 0.001; group 1 vs group 4: NS)
Conclusion: Progesterone administered at the time of neonatal injury prevents an exaggerated
hyperalgesic response to re-injury in adult life and this effect acts, at least partially, through spinal
MAPKs.
133
ANTI-NOCICEPTIVE ROLE OF TUMOR NECROSIS FACTOR-Α (TNF) AT PERIAQUEDUCTAL
GRAY MATTER (PAG) AND ROSTRAL VENTROMEDIAL MEDULLA (RVM) IN RATS.
E. Vazquez, K. Ramirez, C. Osorio, C. Di Giulio, H. Vanegas
Lab. Neurofisiologia/CBB, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela
Background and aims: Increasing evidence suggests that TNF plays an important role in neuronal
excitability, synaptic plasticity and pathological conditions. TNF actions are partly exerted upon
PAG/RVM, whose activity results in nociceptive modulation at the spinal cord and trigeminal nuclei
under normal and pathological states. Here, we investigated whether the microinjection of etarnecept
(a TNF antagonist) into PAG or RVM changes the responsiveness of nociceptive spinal neurons in
normal rats.
Methods: Under deep tiopenthal anesthesia, microinjection cannulae were stereotaxically placed in
PAG or RVM, then single unit recordings were made from wide-dynamic-range neurons of the
superficial spinal dorsal horn. Their receptive field at the ipsilateral hind paw was stimulated for 15 s
every 5 min with calibrated innocuous or noxious clamps. After stable baseline recordings, etarnecept
(12.5 µg/0.5 µl) or vehicle (0.5 µl) was microinjected into ventrolateral PAG or RVM.
Results: Thirty minutes after vehicle microinjection into PAG (n = 5) or RVM (n = 5), spinal neuronal
responses to innocuous or noxious stimulation were similar to baseline. In experimental rats, 30 min
after etarnecept microinjection into PAG (n = 6) or RVM (n = 7) the spinal neuronal responses were
209 % (p< 0.05) and 310 % (p< 0.05) of baseline for noxious, and 278% (p< 0.05) and 440% (p<
0.05) for innocuous stimulation, respectively. Thus, etarnecept into either PAG or RVM increased the
spinal neuronal responses to stimulation.
Conclusions: These results suggest that in normal rats TNF in PAG or RVM contributes to tonic
inhibition of spinal excitability.
134
TRANSCRANIAL MAGNETIC STIMULATION (TMS) - INDUCED 'VIRTUAL LESION' EFFECT ON
EXPERIMENTAL PAIN AND ITS INTERACTION WITH GENDER
1
2
3
3,4
3
I. Weissman Fogel , S. Liem , A. Sinai , D. Yarnitsky , Y. Granovsky
1
2
3
University of Haifa, Haifa, Israel, Utrecht University, Utrecht, The Netherlands, Rambam Health
4
Care Campus, Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel
Background and aims: TMS enables transient and reversible interference with cortical processing
termed 'virtual lesions' (VL). We aimed to elucidate the role of the primary motor cortex (M1) during
exposure to experimental pain by inducing VL. Moreover, we collected psychological factors data
relevant to pain perception.
Methods: Thirty (15 females) healthy individuals underwent two TMS sessions of VL (5 sec, 10 Hz,
90% resting motor threshold) or sham applied to left M1, in random order. The experimental pain
0
consisted of a contact heat (47.5 C) delivered to the right forearm applied alone ('cont´) or
simultaneously with TMS ('test') (at 17-22 seconds after stimulus initiation). Pain ratings were taken
every 10 sec using 0-100 numerical pain scale (NPS). Pain catastrophizing scale (PCS), perceived
stress scale (PSS), and fear pain questionnaire were acquired prior to the experiment and added as
covariates to the analysis.
Results: The outcome measure was change in pain rating following vs. prior to the TMS. An
interaction between gender, type of TMS (VL vs. sham), and condition (test vs. cont) was found
(p=0.027). Post-hoc analysis revealed an effect of VL in females (-18.4, p=0.007) and not in males (7.6, p=0.78). PCS and PSS affected the model (p=0.010 and p< 0.001, respectively) yet, without
gender differences.
Conclusions: Applying VL on M1 during experimental pain show that only females exhibit pain
reduction independently of pain-related psychological factors. These findings suggest that the
functional properties of M1 and probably its interaction with remote interconnected pain related brain
areas, act differently among genders.
135
ABNORMAL ENDOGENOUS PAIN MODULATION IN PATIENTS WITH FUNCTIONAL UPPER GI
PAIN (FUNCTIONAL DYSPEPSIA)
1,2
2
2
C. Wilder-Smith , X. Li , K.Y. Ho , R. Wong
2
1
Gastroenterology Group Practice, Brain-Gut Research Group, Bern, Switzerland,
Neurogastroenterology Unit, Dept. Medicine, National University Singapore, Singapore, Singapore
2
Background and aims: Endogenous pain modulation (EPM) is central to the processing and
integration of afferent sensory information. Visceral and somatic EPM have been shown to be
abnormal in Irritable Bowel Syndrome, but the role of EPM in Functional Dyspepsia (FD) has not been
reported.
Methods: EPM was examined in 34 FD patients (19 females) and 42 healthy controls (25 females)
using a previously validated oral capsaicin pain paradigm and noxious electrical hand stimulation
applied either alone or together with a painful foot heat stimulus for induction of visceral and somatic
EPM (heterotopic stimulation). Cognitive modulation of visceral pain was compared using the
STROOP mental distraction test.
Results: In healthy controls activation of EPM by heterotopic stimulation decreased visceral and
somatic pain (p< 0.02) and distraction reduced visceral pain similarly (p< 0.02). In FD, however,
neither heterotopic stimulation nor distraction reduced visceral or somatic pain significantly.
Decreased effectiveness of visceral EPM correlated with a greater intensity of clinical pain in FD
patients (r=0.57, p< 0.02).
Conclusions: Healthy controls exhibited the expected inhibitory modulation of visceral and somatic
pain. In FD, pain modulation by heterotopic stimulation and by distraction was dysfunctional, with
either decreased pain inhibition or facilitation. The correlation of abnormal pain modulation with
clinical pain in FD suggests a potential pathophysiological significance of abnormal modulation.
409
POTENTIAL ROLE FOR MGLUR5 IN PAIN INHIBITION FROM THE INFRALIMBIC CORTEX IN
RODENTS
A. David-Pereira, S. Puga, A. Almeida, F. Pinto-Ribeiro
ICVS-3Bs Associate Laboratory, Braga, Portugal
Introduction: The prefrontal cortex (PFC), an area primarily involved in cognition, has also been
demonstrated to participate in the descending modulation of pain. Concomitantly, glutamate (GLU)
has been shown to partly mediate the output activity of this area.
Methods: In this work, we aimed at assessing the effects of the transient activation (with GLU) of the
Prelimbic (PrL) and Infralimbic (IL) cortices upon acute nociception, using the paw withdrawal test
(PW) (Hargreaves model).
Results: In control animals, GLU injection in the PrL resulted in increased PW latency
(antinociceptive effect) as soon as 30s after its administration. Interestingly, the administration of GLU
to the IL cortex promoted a long lasting pronociceptive effect (decreased PW latency) that peaked
only 20 minutes after its administration. The use of specific ligands showed that this facilitatory effect
of GLU was mimicked by the administration of metabotrobic GLU receptors type 5 agonists (CHPG).
Moreover, preliminary data showed that these mGLUR5 also facilitate nociception in an animal model
of experimental monoarthritis, demonstrating that this pathway is not disrupted and might thus
contribute to the aberrant pain syndromes so common in clinical conditions.
Conclusions: Our data show that mGLUR5 is a potential player in the facilitation of nociception in
both control and arthritic animals.
410
ROLE OF ACETYLCHOLINE-MEDIATED NEUROTRANSMISSION WITHIN THE NUCLEUS
RAPHE MAGNUS IN THE POST-ICTAL ANTINOCICEPTION
R.C. de Oliveira, R. de Oliveira, T. Paschoalin-Maurin, N.C. Coimbra
Pharmacology, Universidade de São Paulo, Ribeirão Preto, Brazil
Studies have shown cholinergic efferent projections from the pedunculopontine tegmental nucleus to
brainstem structures, such as the nucleus raphe magnus (NRM). Furthermore, muscarinic and
nicotinic receptors within the NRM appear to be involved in the post-ictal antinociception. So, the
present study investigated the role played by M3-muscarinic receptors within the NRM, considered as
an important structure of the endogenous pain inhibitory system, in the organisation of post-ictal
antinociception. Wistar rats, weighing 250g, had the tail-flick baseline recorded and were submitted to
a stereotaxic surgery for the introduction of a guide-cannula aiming at the NRM. After five days, it was
microinjected DAU 5884 at 1µg/0.2µL, 3 µg/0.2µL, 5 µg/0.2µL or physiological saline into theNRM;
after 5 min, tail-withdrawal latencies were measured again from 0 to 130min after seizures evoked by
intraperitoneal injection of pentylenetetrazole (PTZ; 64 mg/kg) or saline. Repeated measures ANOVA
showed statistically significant effect between pretreatments [F(4,32)=13.28; p< 0.001]; of time (0 to
130min) [F(14,19)=7.46; p< 0.01] and pretreatment x time interaction [F(56,70)=2.19; p< 0.05].
Duncan's post hoc test showed statistically significant effect of DAU on post-ictal antinociception from
0 to 130min [F(4,33) varying from 2.71 to 13.08; p< 0.05]. There was not intrinsic statistically
significant effect of DAU into the NRM on nociceptive baseline threshold, neither on latency, severity,
number nor duration of seizures. Pretreatment of the NRM with DAU decreased the post-ictal
antinociception, suggesting the involvement of muscarinic cholinergic mechanisms recruiting M 3
receptors of the NRM in the modulation of pain, during the tonic-clonic seizures.
411
EFFECT OF PAIN INDUCTION AND PAIN INHIBITION ON CONDITIONED PAIN MODULATION IN
ADULTS: A SYSTEMATIC REVIEW
D. Goubert, J. Van Oosterwijck, K. Kolba, H. Noyez, B. Cagnie, L. Danneels, M. Meeus
University Ghent, Ghent, Belgium
Background and aims: Enhanced pain facilitation as well as impaired pain inhibition might be
present in chronic pain patients. A decrease in pain inhibition can be measured by the conditioned
pain modulation (CPM) paradigm. The last few years impaired CPM has been shown in different
chronic pain populations. But it is not yet clear if impaired CPM is the chicken or the egg in chronic
pain conditions and how the presence of pain interferes with the functioning of CPM. This systematic
literature study aimed to provide an overview of the effects of clinical and experimental pain induction
or relief on CPM in adults.
Methods: A systematic literature search was conducted in the databases “Pubmed” and “Web of
Science” using different predefined keyword combinations. In addition articles were screened by hand
searching. Only original research full text articles regarding the effect of clinical and experimental pain
induction and pain relief on CPM in adults were included. The included articles were scored on their
methodological quality and on the applied CPM-paradigm.
Results: Twelve articles were included in this review. Pain inhibiting medication and oral
contraceptives inhibit CPM function. Surgical treatment of chronic pain induced better CPM. This is
not the case in acute pain.
Conclusion: There is limited evidence that surgical removal of the nociceptive source improves CPM
in chronic pain patients. The results suggest CPM is time dependent: only if CPM values are
decreased (like in chronic pain patients) CPM can improve after elimination of pain.
412
THE ROLE OF PAIN MODULATION IN PREDICTING PATIENT DELAY IN SEEKING MEDICAL
HELP IN ACUTE MYOCARDIAL INFARCTION
M. Granot
Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
Background and aims: ST-elevation myocardial infarction (STEMI) is an important cause of
morbidity and mortality. Despite growing awareness of the importance of early reperfusion to prevent
myocardial damage and death, only a minority of STEMI patients seek medical help within the limited
time-window required for optimal treatment. It is not clear why a patient with total occlusion of a
coronary artery and sever chest pain inducing feelings of dread does not seek medical help. This
study aimed to explore whether pain perception and modulation as reflected by advanced
psychophysical assessment influence patient delay in seeking medical help.
Methods: Pain threshold, pain estimation scores, temporal summation and conditioned pain
modulation (CPM) were assessed in 67 STEMI patients with angiographic evidence of complete
blockage of a coronary artery. The associations between these measures and chest pain intensity as
well as duration of patient delay were explored.
Results: Multivariable linear regression analysis revealed that lower chest pain intensity at symptom
onset and exhibiting efficient functioning of the CPM predict 47.3% of the variability of patient delay in
seeking medical help (p=0.034).
Discussion: The finding suggests that an efficient CPM attenuates the perceived intensity of chest
pain evoked at onset of myocardial infarction and leads to patient delay. These findings may serve in
the future to identify patients prone to experience less pain and therefore to feel less hazard as
expressed by delay in seeking medical help.
413
THE EFFECT OF DIFFERENT TYPES OF ACUTE EXERCISE ON PAIN THRESHOLDS IN
CHRONIC PAIN PATIENTS VERSUS CONTROLS: A SYSTEMATIC REVIEW
1
2
1
1
1
L. Hermans , J. Van Oosterwijck , C. Du Four , I. De Wandele , P. Calders , M. Meeus
1
1
2
Department of Rehabilitation Sciences and Physiotherapy, Ghent University, Ghent, Vrije
Universiteit Brussel, Brussel, Belgium
Background: Physical training is a crucial element in the treatment of patients with chronic pain. In
the past, a variety of studies has examined the effect of exercise on pain. These studies used
different modalities of exercise as well as different pain measurements.
Objective: The purpose of this study is to systematically review the scientific evidence regarding the
effect of acute exercises on pain perception in chronic pain patients, specifically in Chronic Fatigue
Syndrome (CFS) and Fibromyalgia (FM), in comparison with the healthy population.
Methods: Systematic review reported following the PRISMA guidelines.
Results: After screening, 16 articles with average to good methodological quality and a sound
exercise and pain protocol were included in the review. We can conclude that chronic pain patients
have an decrease of PPTs (pressure pain thresholds). These exercise induced hyperalgesia was
found in two types of exercise: Isometric and submaximal dynamic exercise, except from one study
using an arm ergometer (submaximal). In healthy people the opposite is seen. Maximal dynamic
exercise was only tested in healthy subjects and generally evoked elevated PPTs, except from one
study using a treadmill instead of a cycle ergometer. However, dynamic exercises of the isolated
muscle resulted in a local decrease of PPTs in healthy people as well.
Conclusion: Generally we could conclude that isometric, submaximal dynamic and maximal dynamic
exercises induce hypoalgesia in healthy people, whereas it increases pain in chronic pain patients. It
also seems that different types and modalities of acute exercise have dissimilar influence on pain
thresholds.
414
INVESTIGATION OF ANTINOCICEPTIVE EFFECTS OF TAURINE AND SOME
PHYTOPREPARATIONS DURING MACROVIPERA LEBETINA OBTUSA VENOM ACTION
M. Hovhannisyan, A. Voskanyan, A. Darbinyan, M. Antonyan
Laboratory of Purification, Certification and Standardization of Physiologically Active Substances, L.A.
Orbeli Institute of Physiology of National Academy of Sciences of Republic Armenia, Yerevan,
Armenia
Background and aims: Snake venoms are a complex of functionally balanced proteins and peptides,
which have a destructive action on the victim's organism. In particular, the Macrovipera lebetina
obtusa (Mlo) venom has a hemorrhagic activity, which leads to blood vessel damage, intra vascular
blood clotting and some other damaging effects. Moreover, the Mlo venom causes a strong pain
syndrome in animals and humans. The antinociceptive effect of taurine is already well known, but the
mechanisms of action are not well studied.
The aim of this study was to evaluate the antinociceptive effect of taurine during Mlo venom action.
Methods: The Hot plate and Tail Flick tests were used. All the procedures were done according to
our institutional animal care and use committee rules and the Ethical Guidelines for Investigations of
Experimental Pain in Conscious Animals.
Results: We have found that taurine and phytopreparation of Plantago major (P. major) have a
significant antinociceptive effect against Mlo venom. The taurine increases the mice jump latency time
almost 2.5 fold and P. major - 1.4 fold. We have also found that some taurine conjugates are highly
toxic and don't exhibit any antinociceptive effect.
Conclusions:
1. The taurine and phytopreparation of P. major expressed an antinociceptive effect when mice
were treated with Mlo venom.
2. The antinociceptive effect of taurine and P. major, along with its antitoxic properties could be
used as a premedical aid against Mlo bite.
3. The taurine conjugates increased the Mlo venom toxicity.
415
EFFECTS OF “SLOW WAVE” AND “LIGHT” SLEEP ON PAIN EXCITATORY AND INHIBITORY
PROCESSES
A. Karmann, L. Killian, S. Lautenbacher
Physiological Psychology, University Bamberg, Bamberg, Germany
Background: Recent evidence suggests a reciprocal relationship between sleep and pain, with
disturbed sleep also increasing the probability and intensity of pain. The restorative function of “slow
wave” sleep has been supposed to be critical for keeping the pain system well-adjusted. For that
purpose, excitatory and inhibitory processes have to be balanced.
Methods: In 38 subjects pain excitatory (temporal summation, TS) and inhibitory processes
(conditioned pain modulation, CPM) were assessed in the evening and morning of two recordings
nights (ambulatory polysomnography at home). The first night served as adaptation night. The sleep
parameters assessed were absolute duration and percentage of “light” (non-REM stage 2) and “slow
wave” sleep (non-REM stage 3+4). Additional pain parameters were pressure pain threshold and
numerical rating of the conditioning stimulus (hot water of 46 °C).
Results: TS was stronger in subjects showing a longer absolute duration of “slow wave” sleep. CPM
showed a similar pattern, with significantly stronger CPM-effects in subjects with a higher percentage
of slow-wave sleep and less “light” sleep (absolute duration). In addition, pain thresholds and ratings
of the painful hot water appeared to be lower in subjects with more “slow wave” sleep and less “light”
sleep.
Conclusion: A sufficient level of “slow wave” sleep - usually associated with a lower level of “light”
sleep - seems to be necessary for pain excitatory as well as inhibitory processes to function properly.
Therefore, this phase of NREM sleep seems to strengthen both processes, keeping them in balance.
416
CONDITIONED PAIN MODULATION (CPM) IS ASSOCIATED WITH HIGH IMPACT CLINICAL
PAIN: THE CASE OF KNEE OSTEOARTHRITIS
1
2
2
3
1
1
Y. Granovsky , I. Kan , B. Peskin , Y. Crispel , D. Yarnitsky , E. Sprecher , M. Granot
4
1
Neurology, Rambam Health Care Campus, Rappaport School of Medicine, Technion Institute of
2
3
Technology, Orthopedic Division, Rambam Health Care Campus, Pediatric Endocrinology and
Clinical Neurophysiology Meyer Children's', Rambam Health Care Campus, Rappaport School of
4
Medicine, Technion Institute of Technology, Nursing, Faculty of Welfare and Health Sciences,
University of Haifa, Haifa, Israel
Background and aims: Although CPM predicts acquisition of future pain, many studies failed to
demonstrate its association with ongoing clinical pain. We explored for this association in patients
before either first knee replacement or those returning for a second surgery, on the not-yet operated
knee.
Methods: Among 35 osteoarthritis patients (58.9±8.1 yrs, 10 males), 20 were scheduled for their first
knee-replacement. All patients underwent preoperative psychophysical pain tests including (CPM;
parallel design, conditioning by hand immersion in 46deg hot water, test pain by Pain60 contact heat).
Results: The two groups were not different in any psychophysical test, and reported similar clinical
pain on the to-be-operated-upon knee. However, pain in the other knee was higher in the first knee
surgery group (35.0±21.4 vs. 19.5±19.5, P=0.034, NPS). In line, the incidence of pain (NPS>20) in the
other knee was higher for the first (14/20, 70%) than the second surgery group (4/15, 27%,
P=0.0176). Separate slopes regression indicated significant group differences between the CPM
relationship to pain (group x slope interaction P=0.0276); less-efficient CPM was associated with
higher pain (r=0.578; P=0.008) for the first surgery group but not for the second (r=-0.221; P=0.429).
Conclusions: High impact clinical pain - pain at more than one bodysite, was required in order to
reveal the association between CPM and clinical pain, possibly due to reliance of multiple site clinical
pain on CPM as a relevant pain modulation mechanism. Thus, the CPM - clinical pain association is
not universal, and seems to depend on the latter´s characteristics.
417
THE EFFECTS OF CHRONIC VAGUS NERVE STIMULATION IN VISCERAL AND NEUROPATHIC
PAIN MODELS
1
2
3
D. Zurowski , J. Wordliczek , J. Dobrogowski , P. Thor
1
2
1
3
Department of Pathophysiology, Department of Pain Treatment and Palliative Care, Department of
Pain Research and Treatment, Jagiellonian University Medical College, Cracow, Poland
Background and aims: A number of studies have established that abdominal vagal afferents
modulate somatic pain behavior. Aims of the present study were to determine whether the vagus play
a role in the endogenous pain inhibitory mechanisms in visceral and neuropathic pain.
Methods: In our study we used the writhing test as a visceral pain model and chronic constriction
injury (CCI) as a neuropathic pain model in rats. We evaluated the effects of subdiaphragmatic
vagotomy on pain threshold and vagal afferents activity. We have also tested two different stimulation
parameters of chronic subdiaphragmatic vagal nerve stimulation: VNS1 (high-intensity) and VNS2
(low-intensity) in two different types of experimental pain models in rats.
Results: Both stimulation parameters increased pain threshold in neuropathic pain. VNS1 was more
effective than VNS2 in visceral pain. We have observed that analgesic effect of VNS occurred only
after several days of stimulation and VNS2 had initially rather slightly facilitatory effect on pain
behavior in CCI rats. Naloxone (opioid antagonist) inhibited the antinociceptive effects of VNS,
reversing partially decrease in the pain threshold in rats with neuropathic pain and increased number
of writhes in visceral pain model.
Conclusions: The present study has confirmed the importance of vagal afferents for nociception and
proven that this role is not limited to somatic pain but also extends to visceral and neuropathic pain.
Our data indicate that analgesic effect of the VNS is mediated by descending opioidergic pathways.
Chronic VNS may have a role in the treatment of visceral and neuropathic pain.
418
RESTORATION OF INFLAMMATION-REACTIVE ASTROCYTES - A NEW CONCEPT AFFECTING
LONG-TERM PAIN
1
2
1
E. Hansson , L. Block , U. Björklund , B. Biber
2
1
2
Clinical Neuroscience and Rehabilitation, Neuroscience and Physiology, Anaesthesiology and
Intensive Care Medicine, Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg,
Gothenburg, Sweden
2+
+
Aims: In astrocytes, restore the following cell parameters: Ca signalling, Na transporters,
cytoskeleton, and release of pro-inflammatory cytokines, which all change in inflammation-reactive
astrocytes.
Methods: Astrocytes in primary cultures were incubated with lipopolysaccharide (LPS) (10 ng/ml) for
24 h to become inflammation-reactive. Different parameters were analysed to verify this inflammation:
2+
+ +
Ca signalling, Na /K -ATPase expression, actin filament organization, and interleukin-1beta release
(IL-1β).
Results: We found that the combination of 1) endomorphin-1, an opioid agonist that stimulates the
Gi/o protein of the µ-opioid receptor; 2) naloxone, an opioid antagonist that inhibits the G s protein of the
µ-opioid receptor at ultralow concentrations; and 3) levetiracetam, an anti-epileptic agent that
+ +
counteracts the release of IL-1β, managed to activate the Gi/o protein and Na /K -ATPase activity,
inhibit the Gs protein, and decrease the release of IL-1β. The disorganized actin filaments were
restored.
Conclusions: The unexpected finding that the cell functions of astrocytes in an inflammatory state
were virtually restored to their normal non-inflammatory state could be of clinical significance and may
be useful for the treatment of long-term pain. Long-lasting pain may partly be a consequence of
ongoing neuroinflammation, in which astrocytes play a significant role.
Significance: These findings put new potential drug regimens towards treatment of long-term pain into
focus.
419
THE EXPRESSION OF GROWTH FACTORS IN THE DORSAL ROOT GANGLION FOLLOWING
HERPES SIMPLEX VIRUS TYPE-1 INFECTION IN MICE
1
2
1
1
1
G. Lucas , F. Cadetti , R. Kusuda , M.I. Ravanelli , C. Almeida , S. Zanon
1
1
2
Physiology, Neuroscience & Behaviour, University of São Paulo, Ribeirão Preto, Brazil
Background and aims: Propagation of herpes simplex virus type-1 (HSV-1) in the dorsal root ganglia
(DRG) produces herpetic and post-herpetic allodynia and hyperalgesia as a result of functional
abnormality of the sensory neurons in mice. Here we investigated the expression profile of nerve
growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor
(GDNF) during virus replication and the latent phase of infection.
Methods: Adult male Balb/C mice were inoculated with HSV-1 on the skin of the left hind. The
expression of NGF, BDNF and GDNF in the DRG extracts was investigated 3, 7, 14 and 21 days after
virus inoculation. Growth factors were measured by ELISA.
Results: Allodynia and hyperalgesia became evident in the hind paw on the inoculated side on day 3
and persisted until at least day 28 (p < 0.05). The application of heat-inactivated HSV-1 induced no
allodynia, hyperalgesia and skin lesion. NGF expression in the DRG was significantly increased from
day 3 to 21 post-infection (p < 0.01). Conversely, HSV-1 inoculation increased BDNF on days 7 and
15 post-infection (p < 0.001) whereas GDNF was marked increased only on day 7 after virus
inoculation (p < 0.01).
Conclusions: These data suggest that herpetic pain may be associated to the phenotypic switch
induced by NGF, BDNF, and GDNF in dorsal root ganglion cells. Moreover, post-herpetic neuralgia
may be associated with increased NGF activity which seems to be a prerequisite for the maintenance
of viral latency.
420
MODULATION OF NOCICEPTIN AND ITS RECEPTOR BY PHORBOL-12-MYRISTATE-13ACETATE VIA SPECIFIC SIGNAL TRANSDUCTION KINASES
L. Zhang, F. Stüber, U.M. Stamer
Bern University Hospital, Bern, Switzerland
Background and aims: Nociceptin and its receptor (NOP) are involved in pain and inflammation.
However, mechanisms involved in their regulation are still unclear. The aim of this study was to
investigate possible signalling pathways contributing to the modulation of nociceptin and NOP.
Methods: The human monocytic cell line MM6 was cultured with/without different concentrations of
phorbol-12-myristate-13-acetatevia (PMA) for 48 hrs. mRNA expression of the nociceptin precursor
(PNoc) and NOP was detected by quantitative RT-PCR. To investigate signalling pathways of
extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK) and nuclear factorkappa B (NF-kB), cells were pretreated with kinase inhibitor PD98509 (30 µM), SB203580 (10 µM),
SP600125 (10 µM) or Bay11-7821 (3 µM) for 1 hr prior to the co-culture with PMA 10 ng/ml.
Intracellular phosphorylated kinases were detected using phospho-flow.
Results: PNoc and NOP mRNA were constitutively expressed in MM6 and regulated dosedependently by PMA. PMA 10 ng/ml induced PNoc after 24 and 48 hrs compared to controls without
any treatment (p< 0.005), whereas NOP expression was attenuated after 6 hrs (p=0.005).
Pretreatment with PD98509, SP600125 or SB203580 completely prevented PMA effects on PNoc. In
contrast, PMA-induced NOP suppression was only partially reversed by PD98509 or SP600125 (p<
0.05). Phospho-flow analysis indicated that pERK, pJNK, p38 and pNF-kB were iduced by PMA in
MM6.
Conclusions: PNoc and NOP mRNA expression were modulated by PMA in MM6. ERK, p38 and
JNK-dependent signal pathways seem to be essential for the regulation of PNoc. ERK and JNK
pathways might contribute to NOP modulation.
421
GLUTAMATE NMDA- AND AMPA-RECEPTORS AS WITH POTENTIAL TARGET FOR
ANALGESIC ACTION OF ANTIDEPRESSANTS
D. Belinskaya, N. Shestakova
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Saint
Petersburg, Russia
Background and aims: Our previous clinical and modeling studies have shown that V-like spatial
group in antidepressant molecules structure is responsible for their analgesic activity.
Electrophysiological experiments have revealed that molecules having this group in their structure can
block glutamate receptors. The aim of the presented study is to model the possible targets for
analgesic activity of antidepressants on glutamate receptors surface.
Methods: Interaction of 3 antidepressants having V-like spatial group and analgesic potencies
(amitriptyline, desipramine, chlorpromazine) and 3 antidepressants having plain aromatic group in
their structure and non-effective for management of pain syndromes (fluoxetine, methiothepin,
clozapine) with NR1 and NR2a subunits of NMDA receptor and GluR2 subunit of AMPA-receptor was
studied by molecular docking procedures using Autodock4.2 software. The data of X-ray analysis of
GluR2, NR1, NR2a subunits and NR1/NR2a complex from Protein Data Bank were used.
Results: All the binding sites of NMDA and AMPA-receptor subunits suitable for sorption of
antidepressants have been determined and examined. The calculations have shown that all the
studied antidepressants can bind effectively with NMDA and AMPA subunits. But the 3D-structure of
the aromatic group of these antidepressants molecules does not affect the effectiveness of
interaction, which is not in agreement with the data of clinical and electrophysiological experiments.
Conclusion: It has been proposed that analgesic action of antidepressants is conditioned by their
binding with glutamate receptor pore.
Supported by: RFBR №12-04-00454-а.
422
INVOLVEMENT OF CB1 AND CB2 CANNABINOID RECEPTORS OF PERIPHERAL TISSUE IN
THE ANTI-HIPERLGESIC EFFECT OF DYPIRONE AND ITS BIOACTIVE METABOLITES
G.G. dos Santos, J.T. Maia, E.V. Dias, M.C.P. Athie, C.A. Parada
University of Campinas, Campinas, Brazil
Background and aim: Dypirone is an analgesic pro-drug widely used to control moderate pain. It is
fast metabolized in two bioactive metabolites: 4-methyl-amino-ntipyrine (4-MAA) and 4-aminoantipyrine (4-AA). In Central Nervous System, their analgesic effect has been associated with the
activation of CB1 and CB2 cannabinoid receptors. The aim of this study was to investigate the
participation of peripheral CB1 and CB2 cannabinoids receptors in peripheral tissue on the antihyperalgesic effect of Dypirone, 4-MAA or 4-AA.
Methods: The experiments were performed using male Wistar rats (200-230g). The mechanical
nociceptive threshold was quantified by an electronic pessure-meter test (von Frey). Excepted to
PGE2 (100ng / paw), ODQ (32 µg) and glibenclamide (80 µg ) a dose-response curve were performed
to all drugs used, which were locally injected (50 µL /paw) in the subcutaneous tissue of hindpaw.
Results: The intraplantar administration of PGE2 induced mechanical hyperalgesia, which was
inhibited by dypirone, 4-MAA, and 4-AA (all 286.7 - 455.84 µM) injected 30 minutes before the von
Frey test. The selective CB1 receptor antagonist AM251, but not the selective CB2 receptor
antagonist AM630, administered 30 min before 4-AA reversed its anti-hyperalgesic effect. Neither
AM251 nor AM630 reversed the anti-hyperalgesic effect of dypirone or 4-MAA administered 30
minutes before, which were reversed by cGMP inhibitor, ODQ or K-ATP ion channel blocker,
glibenclamide.
Conclusion: These results suggest that the mechanisms of anti-hyperalgesic action of dypirone in
the peripheral tissue involve the activation of CB1 receptor by 4-AA and cGMP-K-ATP pathway by 4MAA.
Financial support: CAPES-Brazil
423
TRPV1 AND CALMODULIN INTERACTION
1
1
1
2
2
2
3
1
K. Josvay , A. Buhala , Z. Winter , T. Martinek , E. Weber , L. Nemeth , A. Hetenyi , E. Kalmar , G.
1
1
1,4
Dombi , G. Szakonyi , Z. Olah
1
2
Institute of Pharmaceutical Analysis, Institute of Pharmaceutical Chemistry, Faculty of Pharmacy,
3
4
University of Szeged, Institute of Medical Chemistry, University of Szeged, Acheuron Hungary Ltd.,
Szeged, Hungary
Background and aims: Transient receptor potential vanilloid 1 (TRPV1) is a nonselective, Na+/Ca2+
permeable cation channel, involved in inflammatory pain and in a wide range of non-pain-related
physiological and pathological conditions. TRPV1 can be activated by different stimuli, including heat,
acidification, exo-vanilloids such as capsaicin and resiniferatoxin, and the endogenous anandamide.
Agonist-induced multiple Ca2+-influx leads to desensitization of TRPV1 to painful stimuli, and
Ca2+/calmodulin dependent phosphatase and kinase activation is also involved in this tachyphylaxia.
There are two calmodulin binding sites at the N- and C-cytoplasmic region of TRPV1, respectively.
Our aim was to determine the structural features of these regions and examine endo- and exogenous
factors affecting CaM-TRPV1 interactions that leads to either desensitization or tachyphylaxia.
Methods: DNA cloning, protein purification, SDS-PAGE, western blot, protein binding and pull down
assays.
Results: We have overexpressed calmodulin, as well as the N-terminal ARD-repeats and the Cterminal cytolplasmic region of the human TRPV1 with GST and His6 fusion tags in Escherichia coli
bacteria, and purified these peptides by affinity chromatography. We have shown, that exogenous
compounds from plants and fungi may influence CaM-ARD-TRPV1 and CaM-TRPV1-C' binding,
therefore they may have impact on desensitization and tachyphylaxia. We will further examine the
purified peptides in co-crystallization experiments and NMR studies.
Conclusions: Desensitization of the TRPV1 receptor and subsequent tachyphylaxia is a basis of
several pain relief methods and medications. Better understanding of the influencing factors and
structural determinants could lead us to the exploration of potentially useful drugs and development of
new targeted therapies.
424
IMPACT OF THE INCORPORATION OF UNNATURAL AMINO ACIDS AT THE C-TERMINAL END
OF THE APELIN PEPTIDE ON PAIN INHIBITION
1
2
2
1
2
3
2
M. Lafrance , A. Murza , E. Besserer-Offroy , J.-M. Longpré , R. Leduc , T. Stroh , E. Marsault , P.
1
Sarret
1
2
Department of Physiology and Biophysics, Department of Pharmacology, Université de Sherbrooke,
Montreal Neurological Institute and Hospital, McGill University, Sherbrooke, QC, Canada
3
Background and aims: The apelin peptide has been identified as the endogenous ligand for the
human G protein-coupled receptor “APJ”. Despite its widespread pattern of distribution in the brain,
the apelinergic system is highly expressed in brain areas involved in pain modulation.
Methods: To further elucidate the role of the apelinergic system in the regulation of pain transmission,
12
13
we synthesized a series of apelin-13 analogs in which the C-terminal Pro and Phe were substituted
by unnatural amino acids. The analgesic potencies of these new chemical entities were then
investigated using the persistent inflammatory pain model of formalin.
12
Results: Toward this end, Pro was substituted by aminoisobutyric acid (Aib) in the Ape13Met11Nle
13
and the terminal Phe residue was replaced by the aromatic residues 1Nal or 2Nal. Following
intrathecal administration, both Pro12Aib and Phe13-2Nal analogs were effective in reversing the
spontaneous pain behaviors induced by intraplantar formalin. In contrast, spinal delivery of the
Phe13-1Nal derivative did not produce antinociceptive responses in both phases of the formalin
model. Interestingly, Phe13-1Nal and Phe13-2Nal exhibited distinct G protein-coupling and b-arrestin2 recruitment profiles following binding to APJ.
Conclusions: Altogether, these results suggest that the APJ receptor represents a promising
therapeutic target for the management of persistent pain. These data also reveal that modification at
the C-terminal end of the apelin peptide leads to the formation of biased ligands that might have
profound influences on the pain signal processing.
425
POORLY CONSERVED RESIDUES WITHIN THE TRANSMEMBRANE DOMAINS 5 AND 6
DICTATE A SPECIES-SPECIFIC ACTIVATION OF HUMAN TRPA1 BY PROTONS
1
1
2
1
2
2
2
J. de la Roche , M.J. Eberhardt , A.B. Klinger , W. Koppert , P.W. Reeh , A. Lampert , M.J. Fischer ,
1
A. Leffler
1
2
Dept. of Anesthesiology and Intensive Care, Hannover Medical School, Hannover, Institute of
Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen,
Germany
Background and aims: The surveillance of acid-base homeostasis is concerted by diverse
mechanisms, including an activation of sensory afferents. Proton-evoked activation of rodent sensory
neurons is mainly mediated by the capsaicin receptor TRPV1 and acid sensing ion channels. In this
study we demonstrate that extracellular acidosis activates and sensitizes the human irritant receptor
TRPA1 (hTRPA1).
++
Methods: Patch Clamp and Ca imaging recordings were performed on wild-type, TRPA1-/- and
TRPV1-/- mouse dorsal root ganglion neurons and HEK293t cells expressing constructs of human,
rhesus monkey or rodent TRPA1.
Results: Proton-evoked membrane currents and calcium influx through hTRPA1 occurred at
physiological acidic pH-values, were concentration-dependent, and blocked by the selective TRPA1
antagonist HC030031. Both rodent and rhesus monkey TRPA1 failed to respond to extracellular
acidosis, and protons even inhibited rodent TRPA1. Accordingly, mouse dorsal root ganglion neurons
lacking TRPV1 only responded to protons when hTRPA1 was heterologously expressed. This species
specific activation of hTRPA1 by protons was reversed in both mouse and rhesus monkey TRPA1 by
exchange of distinct residues within transmembrane domains 5 and 6. Furthermore, protons seem to
interact with an extracellular interaction site to gate TRPA1 and not via a modification of intracellular
N-terminal cysteins known as important interaction sites for electrophilic TRPA1-agonists.
Conclusions: Our data suggest that hTRPA1 acts as a sensor for extracellular acidosis in human
sensory neurons and should thus be taken into account as a yet unrecognized transduction molecule
for proton-evoked pain and inflammation. The species specificity of this property is unique among
known endogenous TRPA1-agonists.
426
INHERITED PAIN: SODIUM CHANNEL NAV1.7 A1632T MUTATION CAUSES
ERYTHROMELALGIA DUE TO A SHIFT OF FAST INACTIVATION NOT OF ACTIVATION
1,2
2
2
2
3
2
2
M. Eberhardt , J. Nakajima , A.B. Klinger , C. Neacsu , K. Hühne , A.O. O'Reilly , A.M. Kist , A.K.
4
5
6
5
3
2
Lampe , K. Fischer , J. Gibson , C. Nau , A. Winterpacht , A. Lampert
1
Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover,
3
Institute of Physiology and Pathophysiology, Department of Human Genetics, Friedrich-Alexander
4
Universität Erlangen-Nürnberg, Erlangen, Germany, South East of Scotland Clinical Genetic Service,
5
Western General Hospital, Edinburgh, UK, Department of Anesthesiology, Friedrich-Alexander
6
Universität Erlangen-Nürnberg, Erlangen, Germany, Fife Rheumatic Diseases Unit, Whyteman's
Brae Hospital, Kirkcaldy, UK
2
Background and aims: Inherited Erythromelalgia (IEM) causes debilitating episodic neuropathic pain
characterized by burning in the extremities. Inherited “paroxysmal extreme pain disorder” (PEPD)
differs in its clinical picture and affects proximal body areas like rectal, ocular or jaw regions. Both pain
syndromes have been linked to mutations in the voltage-gated sodium channel Nav1.7.
Electrophysiological characterization so far reveals that IEM-causing mutations generally enhance
activation whereas mutations leading to PEPD alter fast inactivation. Previously an A1632E mutation
of a patient with overlapping symptoms of IEM and PEPD was reported (Estacion et al. 2008),
displaying a shift of activation and fast inactivation. Aim of this study was to characterize a new
mutation of Nav1.7, A1632T, found in a patient suffering from IEM.
Methods: Nav1.7 and its mutants were expressed in HEK cells and investigated by whole-cell
voltage-clamp. In order to assess the structural implications of different amino acids we substituted
A1632 with D/E/K/T/V for electrophysiolgical analysis.
Results: Surprisingly, Nav1.7 activation was unaltered by the A1632T mutation, but steady-state fast
inactivation was shifted to more depolarized potentials, a characteristic normally attributed to PEPDcausing mutations. In contrast to the IEM/PEPD crossover mutation A1632E, A1632T failed to
increase resurgent currents, which have been suggested to contribute to high frequency firing in
physiological and pathological conditions.
Conclusions: Reduced fast inactivation without increased resurgent currents induces symptoms of
IEM in the new Nav1.7 mutation A1632T. Therefore resurgent currents are likely to determine whether
a mutation in Nav1.7 leads to IEM or PEPD.
427
PROSTAGLANDIN E1 FACILITATES HYPERPOLARIZATION-ACTIVATED CYCLIC
NUCLEOTIDE-GATED (HCN) CHANNEL THROUGH ACTIVATION OF THE EP 2 SUBTYPE IN
SOMATOSENSORY NEURONS
1
2
1
1
1
J. Moon , I. Kang , Y.C. Kim , E. Kim , K. Park , G. Nahm
1
1
2
Seoul National University Hospital, Seoul, Seoul National University Bundang Hospital, Bundang,
Republic of Korea
Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels and their current, Ih, have
been reported to play an important role in neuropathic pain by involvement in ectopic discharges after
peripheral nerve injury. Prostaglandin E1 (PGE1), known as its powerful vasodilatory effect, has been
suggested as a therapeutic agent for lumbar spinal stenosis in clinical fields. The present study
investigated the cellular action of PGE1 on HCN ion channel in primary dissociated neurons of
trigeminal ganglia (TG) in rats. Medium-sized TG neurons were prepared and whole-cell recordings
were made using patch electrodes. Ih was identified in the medium-sized TG neurons isolated from
rats and increased about 130% by PGE1. PGE1 facilitated I h current in a dose-dependent manner
(ED50 = 29 nM). Adenylyl cyclase inhibitor and 8-Br-cAMP inhibited the fascilitation of Ih current by
PGE1. EP2 receptor antagonist inhibited the facilitation of I h current by PGE1. Exposure to PGE1
enhanced their excitability by increasing action potential frequency in I h-expressing TG neurons.
PGE1 facilitated Ih current in medium-sized TG neurons in rats, which was mediated by EP2 receptor
by transmitting a signal to adenylyl cyclase and increasing the intracellular concentration of cAMP.
Exposure to PGE1 would control the firing of action potential by enhancing their excitability in Ihexpressing TG neurons.
428
THE Α2Δ-3 SUBUNIT, A NEW PLAYER IN HEAT SENSATION OF PRIMARY SENSORY
NEURONS!
1
2
2
F. Mayer , S. Geisler , G.J. Obermair , J. Hu
1
1
Sensory Mechanotransduction, Centre for Integrative Neuroscience, University of Tübingen,
2
Tübingen, Germany, Physiology and Medical Physics, Medical University of Innsbruck, Innsbruck,
Austria
Background & aims: The α2δ-3 subunit has been shown involved in heat-sensation in different
1
species . The mechanism is still unclear but thought to mainly happen in the brain. In the present
study we investigated the expression and function of α2δ-3 in primary sensory neurons and spinal
cord under normal and neuropathic pain conditions. We propose a more peripheral role of it in the
somato-sensory-system.
Methods: Standard pain tests have been done on male adult α2δ-3 knock-out mice and wild-type
littermates. Chronic-Constriction-Injury (CCI) was performed as a neuropathic pain model. Calcium
imaging, whole cell patch clamp on primary sensory neurons and ex vivo skin-nerve recordings were
performed to investigate heat sensitivity alteration.
Results: α2δ-3 is expressed in DRG and spinal cord. Reduction of heat sensitivity was observed in
both, hot plate test and DRG neurons recordings. After nerve injury, recovery from hypersensitivity
was significantly slower in the α2δ-3 knock-out mice. Real-time PCR showed a down-regulation of the
mRNA after injury.
Conclusion: Our results suggest that α2δ-3 is expressed in primary sensory neurons. Its deficit alters
the heat nociception information processing on the DRG and spinal cord level and delays the
recovery after nerve injury.
Reference: 1. Neely, G.G., Hess, A., Costigan, M., Keene, A.C., Goulas, S., Langeslag, M., Griffin,
R.S., Belfer, I., Dai, F., Smith, S.B., et al. (2010). A genome-wide Drosophila screen for heat
nociception identifies alpha2delta3 as an evolutionarily conserved pain gene. Cell 143, 628-638.
Acknowledgement: Supported by the CIN (funded by the Deutsche Forschungsgemeinschaft, EXC
307).
429
THE ROLE OF NAV1.8 VS. TTX-S CHANNELS IN COLD EVOKED RESPONSES OF RATS
S. McMurray, A.R. Brown, E. Stevens, G. McMurray, P.J. Cox
Ion Channel Pharmacology, Neusentis Pfizer, Cambridge, UK
Background and aims: Through the use of Nav1.8 KO mice previous published data (Zimmermann
K et al, 2007) has shown that Nav1.8 channels mediate cold evoked responses in DRGs and to some
extent nerve firing as measured with single unit recordings from skin saphenous nerve preparations.
To our knowledge this has never been shown using a selective Nav1.8 blocker.
Methods: Acutely dissociated rat DRGs were utilised for whole cell patch clamp studies, in current
clamp configuration, where single action potentials were evoked using a 5 ms suprathreshold current
step at a frequency of 0.1Hz. Cells were continually perfused with extracellular solution (ECS), in the
presence of TTX, Compound A (a selective Nav1.8 inhibitor), A-803467 or vehicle, and the bath
temperature was switched between 21C and 10C (typically 60-90s). To determine functional
physiological effects of Na+ channel blockade against cold evoked afferent nerve firing, the rat skin
nerve preparation was utilised. Multi -unit recordings from cold sensitive afferent fibres of the tibial
nerve in the presence of TTX, compound A, A-803467 or vehicle were investigated.
Results: Action potential generation in acutely dissociated rDRGs is maintained at 10C. TTX blocks
APs at 21C but has no effect on APs evoked at 10C indicating a shift from TTX-s to TTX-r dominated
APs at low temperature. TTX significantly reduces evoked afferent firing in the rat skin nerve
preparation.
Conclusions: The cold evoked response in rats is not purely mediated by Nav1.8 channels.
Zimmermann K et al; Nature 2007 Jun 14;447 (7146):855-8
430
PELLITORINE: A POTENT ANTAGONIST OF THE INFLAMMATORY PAIN/VANILLOID
RECEPTOR TYPE 1 FROM THE FRUITS OF TETRADIUM DANIELLII
1
2
3
1
1
2
1
Z. Oláh , D. Rédei , C. Vizler , K. Jósvay , L. Pecze , P. Forgó , Z. Winter , J. Hohmann
1
2
2
3
Institute of Pharmaceutical Analysis, Department of Pharmacognosy, University of Szeged, Institute
of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged,
Hungary
Background and aims: Vanilloid receptor type 1 (TRPV1), confers noxious heat and inflammatory
pain signals in the peripheral nervous system. Evodia species, used in traditional medicine, are
recognised source of different TRPV1 agonists, but no antagonist has been found. We aimed to
investigate different Rutaceaes to find extractable vanilloid analogs targeting TRPV1 either as
agonists or antagonists.
Methods: The plant extracts were fractionated using different chromatographic techniques and the
fractions were further investigated using NMR spectroscopy. The activity of the fractions was tested in
45
2+
a capsaicin-induced Ca -uptake in TRPV1-HaCaT keratinocyte cell line. The active compound was
purified to homogeneity.
st
Results: Seeking for painkiller leads, we noted for the 1 time TRPV1 antagonist activity in the fresh
fruits of Tetradium daniellii (Benn.) T.G. Hartley (syn. Evodia hupehensis Dode). We have isolated a
new painkiller candidate that is a distant structural homologue, but competitive inhibitor of capsiate
exovanilloids and endovanilloids such as anandamide. Determination of the chemical structure with
1
13
H- and C-NMR have revealed pellitorine (2E,4E)-N-(2-methylpropyl)deca-2,4-dienamide that
structurally can compete with algesics released in inflammation. Contrary to previous isolates from
2+
Evodia species, pellitorine blocked capsaicin-evoked Ca -uptake with an IC50 of 79 mg/ml. Nisobutyl-4,5-epoxy-2E-decadienamide and furocoumarines were also co-purified with our method, but
none of them affected TRPV1.
st
Conclusions: Our studies provide the 1 evidence that pellitorine, an aliphatic alkylamide analogue
of capsaicin, can serve as full antagonist of TRPV1 and may inhibit exo-, and endovanilloid-induced
pain, inflammation and neuropathies, in vivo.
431
SLP3 MODULATES MAMMALIAN TOUCH SENSITIVITY VIA LIPID RAFTS
1,2
1,3
M.Y. Qi , F. Frattini , J. Hu
1
1
Sensory Mechanotransduction, Centre for Integrative Neuroscience (CIN), University of Tübingen,
3
Graduate School of Cellular & Molecular Neuroscience, University of Tübingen, Graduate School of
Neural & Behavioural Sciences, University of Tübingen, Tübingen, Germany
2
Backgroud and aim: Touch-evoked pain is a frequent symptom of neuropathic pain for which
effective treatment is lack. Understanding mechanosensation on transduction level would potentially
promote the management of allodynia. However, the mechanism of sensory mechanotransduction
remains unclear. It has been demonstrated that cholesterol is required for touch sensation in C.
elegans through MEC2. In mouse, knocking out SLP3, a mammalian homologue of MEC2, leads to
loss of mechanosensitivity in about 30% of primary sensory neurons But how SLP3 contributes to
mechanotransduction remains puzzling. Here we propose that SLP3 modulates touch sensitivity via
binding to cholesterol enriched lipid rafts.
Methods and results: To determine if lipid rafts affect mechanotransduction, MßCD was applied to
deplete membrane cholesterol in cultured mouse DRG neurons, and mechanically activated current
was recorded. MßCD treatment significantly reduced mechanosensitivity in sensory neurons from
wild-type mouse but did not induce a further reduction of mechanosensitivity in SLP3-/- neurons.
Moreover, we identified a SLP3 mutant that shows deficiency in associating with lipid rafts-like
microdomain. Reconstitution of this mutant into SLP3-/- neurons failed to rescue the loss of
mechanosensitivity as wild type did. Intriguingly, in vivo intraplantar injection of MβCD alleviated
mechanical allodynia induced by chronic constriction injury (CCI) in wild-type but not in SLP3-/- mice.
Conclusion: Altogether, our data suggests that lipid rafts-like microdomain plays an essential role in
mouse sensory mechanosensation through SLP3 binding to cholesterol. Our work would provide
potential therapeutic target for neuropathic pain.
Acknowledgement: Supported by CIN (funded by the Deutsche Forschungsgemeinschaft, EXC
307).
432
ACTIONS OF PHΑ1Β PEPTIDE PURIFIED FROM THE BRAZILIAN SPIDER PHONEUTRIA
NIGRIVENTER VENOM ON ADVERSE EFFECTS CAUSED BY MORPHINE IN MICE
1
1
1
2
R. Tonello , F. Rigo , C. Gewehr , M. Gomez , J. Ferreira
1
3
2
Federal University of Santa Maria, Santa Maria, Federal University of Minas Gerais, Minas Gerais,
Federal University of Santa Catarina, Florianópolis, Brazil
3
Background and aims: Opioids are the standard therapy for the management of several kinds of
pain, however their use is limited by adverse effects, such as constipation tolerance, hyperalgesia and
withdrawal syndrome. Voltage-dependent calcium channel (VDCC) is involved in analgesia, but its
role on opioid-induced side effects is little known. Thus, the goal of this study was to evaluate the
possible actions of the peptide Phα1β, a VDCC blocker, on the antinociceptive and the adverse
effects produced by single or repeated administration of morphine in mice.
Methods: We evaluated the effect of Phα1β on mechanical and heat hyperalgesia, tolerance,
constipation and withdrawal syndrome induced by repeated administration of morphine in mice
th
(increasing doses 3 times a day for 3 consecutive days). In the 4 day, the mice received a morphine
(10 mg/kg, subcutaneously) or saline challenge and were treated with Phα1β (0.01-30 pmol/site,
intrathecally) or vehicle.
Results: Repeated treatment with morphine caused not only tolerance to its antinociceptive effect,
but also produced hyperalgesia in treated mice. The injection of Phα1β (0.1-30 pmol/site) was able to
reverse both mechanical and heat hyperalgesia induced by morphine, from 1 and 2 hours after the
treatment. Furthermore, Phα1β (0.1 pmol/site, i.t.) also partially recovered the antinociceptive effect of
morphine in tolerant mice. Repeated treatment with morphine induced constipation and withdrawal
syndrome, both effects were also partially reversed by the treatment with Phα1β (30 pmol/site, i.t.).
Conclusions: Phα1β was effective over hyperalgesia, tolerance, constipation and withdrawal
syndrome induced by repeated administration of morphine in mice.
433
THE EFFECTS OF THERMOSENSITIVE TRP CHANNEL AGONISTS ON TEMPERATURE AND
PAIN SENSATIONS BY COLD PLATE TEST
M. Tsagareli, I. Nozadze, G. Gurtskaia, N. Tsiklauri, Pain Research
Neurophysiology, Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia
Background and aims: The thermo TRP channels are capable of the detection of temperature, as
well as mechanical and chemical stimuli. In this study, using behavioral cold plate test we investigated
whether capsaicin and allyl isothiocyanates (AITC) affect sensitivity to innocuous and noxious cold in
male rats.
Methods: To tests sensitivity to cold temperatures, rats received bilateral intraplantar injections of
capsaicin, AITC and vehicle and 5 min later was placed onto the thermoelectric surface that was set
at +5°C, 0°C or 5°C. The latency for nocifensive behavior (lifting and licking one hind paw, or jumping)
was measured, at which point the rat was immediately removed. All animals were retested 5 min, 30
min, 60 min, 90 min and 120 min post-injections. Cold plate latencies were normalized to pretreatment baselines and compared between several concentrations of capsaicin, AITC and vehicle
treatment groups by ANOVA and t-test.
Results: Bilateral intraplantar injection of capsaicin and AITC induced a significant, concentrationdependent reduction in cold plate latency compare to vehicle controls. However, there were no
antinociceptive effects in latency at the +5°C, 0°C and -5°C temperatures. Note that in the -5°C cold
plate test, AITC treatment resulted in the high significant difference between vehicle (mineral oil) and
AITC treated groups (P< 0.001).
Conclusions: Presented data support a role thermosensitive TRP channels in pain modulation, and
that these thermoTRP channels represent promising targets for the development of new analgesic
drugs.
Acknowledgements: This study was supported by the grant from National Science Foundation of
Georgia (#1/6-27).
434
PHENOTYPE HETEROGENEITY IN A FAMILY WITH COMPLEX NAV1.7 MUTATIONS
1
1
2
V. Tugnoli , V. Simioni , T. Pierro , G. Lauria
1
2
2
Neurophysiologic Unit, S.Anna Hospital, Ferrara, Neuromuscular Diseases Unit, IRCCS Foundation,
'Carlo Besta' Neurological Institute, Milan, Italy
Background and aims: Recent papers demonstrated that SCN9A mutations encoding for Nav1.7
can explain the pathogenesis of neuropathic pain in idiopathic small fibre neuropathy (SFN).
Methods: The proband, a 23 year-old woman complaining of severe pain in the distal extremities and
her father underwent clinical evaluation, skin biopsy, and neurophysiologic (NPH) examination
including nerve conduction study (NCS), thermal quantitative sensory testing (QST), Laser Doppler
Flowmetry (LDF) and Laser Evoked Potentials (LEP).
Results: The proband complained of severe neuropathic pain for 4 years, paroxysmal crisis, positive
sensory signs and autonomic symptoms and signs. NCS and LEP were unremarkable, whereas skin
biopsy demonstrated a reduced epidermal innervation at the distal leg. QST showed increased
thermal threshold and thermal allodynia distally in the lower and upper limbs, respectively.
We identified three allelic mutations in SCN9A (2794A>C M932L; 2971G>T V991L; 4612T>C
W1538R). Two of them (M932L and V991L) were previously found in SFN and their pathogenicity
demonstrated by voltage and current-clamp assay. Her father was asymptomatic with normal clinical
and NPH examinations. Conversely, skin biopsy showed a significant decrease of distal epidermal
innervation.
Conclusions: We report a family harboring two pathogenic mutations in SCN9A associated with a
further one which role is yet unknown. The heterogeneity of the phenotype observed in the two
carriers of the same complex mutations, both disclosing the degeneration of epidermal nerve fibres
but only one showing altered small fibre functions and complaining of severe neuropathic pain,
suggests that unknown epigenetic and/or genetic pain-inducing or protective factors may exist.
435
HISTAMINE MODULATION OF ACUTE NOCICEPTION INVOLVES REGULATION OF NAV1.8 IN
PRIMARY AFFERENT NEURONS IN MICE
1
1,2
1
1
1
1
1
2
J. Yu , Q. Fang , G.-D. Lou , W.-T. Shou , J.-X. Yue , Y.-Y. Tang , W.-W. Hou , T.-L. Xu , H.
3
1
1
Ohtsu , S.-H. Zhang , Z. Chen
1
Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of
China, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou,
2
3
College of Basic Medicine, Shanghai Jiaotong University, Shanghai, China, Graduate School of
Engineering, Tohoku University, Aoba-ku, Japan
Aims: To explore the role of histamine in acute pain perception and its possible mechanisms.
Methods: Pain-like behaviors induced by four types of noxious stimuli (hot-plate, tail-pressure, acetic
acid and formalin) were accessed in mice. Nav1.8 expression and functions in primary afferent
-/neurons were compared between histidine decarboxylase knockout (HDC ) mice and their wild-types.
-/-
Results: HDC mice, lacking in endogenous histamine, showed elevated sensitivity to all these
noxious stimuli, as compared with the wild-types. In addition, a depletion of endogenous histamine
with α-fluoromethylhistidine (α-FMH), a specific HDC inhibitor, or feeding mice a low-histamine diet
also enhanced nociception in the wild-types. Nav1.8 expression in primary afferent neurons was
-/increased both in HDC and α-FMH-treated wild-type mice. A higher Nav1.8 current density, a lower
current that was required to evoke action potentials and a higher firing rate in response to
-/suprathreshold stimulation were observed in nociception-related small DRG neurons of HDC mice.
Nav1.8 inhibitor A-803467, but not TTX, diminished the hyperexcitability of these neurons.
Conclusion: Our results indicate that histamine participates in acute pain modulation in a doserelated manner. The regulation of Nav1.8 expression and the excitability of nociceptive primary
afferent neurons may be involved in the underlying mechanisms.
436
REDUCED WIDESPREAD EXPERIMENTAL PAIN TOLERANCE AMONG ADOLESCENTS WITH
CHRONIC ABDOMINAL PAIN
1
1,2
3,4
N. Stabell , T. Flægstad , A. Stubhaug , C.S. Nielsen
1
5
2
3
Dept of Pediatrics, University Hospital in Northern Norway, University of Tromsø, Tromsø, Dept of
4
Pain Management and Research, Oslo University Hospital, Faculty of Medicine, Oslo University,
5
Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway
Aims: The aim in this study was to analyze associations between chronic abdominal pain (CAP) and
experimental pain tolerance among adolescents in the general population.
Methods: Pain tolerance for cold-pressor, heat, and pressure (finger nail and shoulder) stimuli was
measured in 961 adolescents (15-17 year old) in a cross-sectional study performed in 2010-2011.
Questionnaire data included abdominal pain intensity ratings (numeric rating scale 0-10), comorbid
chronic pain and symptoms of depression (Short Mood and Feeling Questionnaire score ≥ 11).
A stepwise Cox proportional hazards model was applied to compare pain tolerance times between
CAP subgroups (no, mild, moderate and severe abdominal pain), controlling for sex, comorbid chronic
pain and depression in the second step.
Results: Reduced pain tolerance was associated with degree chronic abdominal pain and was
significantly reduced (p < 0.01) for participants with severe CAP compared to controls (Hazard ratio =
2.2, 1.8, 2.5 and 2.0 for the cold-pressor, heat pain, pressure pain - finger, and pressure pain shoulder, respectively). The cold-pressor and pressure pain - finger results remained significant (p <
0.05) after adjusting for sex, comorbid chronic pain and depression (see Figure).
Conclusions: Reduced widespread pain tolerance was found among adolescents with severe CAP,
which may contribute to the high prevalence comorbid pain and depression.
[Pain tolerance in CAP]
437
TOLERANCE EFFECTS OF NSAIDS MICROINJECTED INTO THE DORSAL HIPPOCAMPUS
N. Tsiklauri, G. Gurtskaia, I. Nozadze, M. Tsagareli
Neurophysiology, Ivane Beritashvili Center of Exp. Biomedicine, Tbilisi, Georgia
Background and aims: Several lines of investigations have shown that in some brain areas, the
PAG, RVM, central amygdala, and raphe nuclei, micro-injections of NSAIDs causes antinociception
with some effects of tolerance. The present study was designed to examine whether microinjection of
NSAIDs, ketorolac, xefocam and clodifen into the dorsal hippocampus (DH) leads to the development
of antinociceptive tolerance in male rats.
Methods: Adult white albino male rats were used in this study. Steel cannula was stereotaxically
implanted into the DH uni- and bilaterally, and four days after the surgery NSAIDs were microinjected
in the volume of 0.5µl for four consecutive days. The tail-flick reflex (TF) and hot plate (HP) latencies
were measured as a parameter of antinociception. Same volume of saline was injected into the DH for
control animals.
Results: We found that microinjection of ketorolac, xefocam and clodifen into the DH induces antinociception as revealed by a latency increase in TF and HP latencies compared to controls with
saline. Subsequent testing, however, showed that the antinociceptive effect progressively decreased
during the following days as a consequence of repeated microinjections. Pretreatments as well as
post-treatments with µ-opioid antagonist naloxone significantly decreased analgesia to NSAIDs that
indicates opioid sensitivity to these antinociceptive and tolerance effects. Our results, thus, strongly
indicate the development of tolerance to administrations of ketorolac xefocam and clodifen into the
DH.
Conclusions: Presented data confirmed previous studies indicating that the antinociceptive action of
NSAIDs and the development of tolerance may be closely related to endogenous opioids.
438
EFFECT OF RUFINAMIDE AND OXCARBAZEPINE ON PERIPHERAL NERVE EXCITABILITY
L.M. Macrea, M. Kolb, D.R. Spahn, K. Maurer
University Hospital Zurich, Institute of Anesthesiology, Zurich, Switzerland
Background and aims: Systemic sodium channel blockers are successfully used in the treatment of
neuropathic pain. However, their impact on the peripheral nervous system remains unclear. The aim
of this study was to evaluate the effect of rufinamide and oxcarbacepine on axonal excitability of
peripheral sensory nerves.
Methods: After obtaining institutional ethics committee approval (KEK-ZH-Nr. 2010-0068) and written
informed consent, we included 24 healthy volunteers in a randomized, double-blinded, placebocontrolled, crossover study. Over a 10-day period the drugs were gradually increased up to a
therapeutic level. We measured nerve excitability parameters of sensory afferents on the median
nerve (strength-duration time constant, the recovery cycle after a supramaximal stimulus and
threshold electrotonus) using computerized threshold tracking technique (QTRAC®).
Results: Rufinamde affected significantly superexcitability, depolarizing threshold parameters and
refractoriness of both, sensory and motor nerve fibers. Oxcarbazepine showed similar changes on
motor fibers. However, oxcarbazepine changed significantly peak response, subexcitability and
refractoriness in sensory fibers.
Conclusion: Threshold tracking techniques are a suitable tool to measure effects of systemic sodium
channel blockers on peripheral nerve excitability. Oxcarbazepine showed a differential effect on
sensory peripheral nerve.
439
USE OF ANTIDEPRESSANTS IN A CHRONIC PAIN UNIT IN PORTUGAL - A RETROSPECTIVE
STUDY
1
2
P. Garrido , L. Pereira , A. Valentim
1
2
2
Psychiatry, Anesthesiology, Coimbra Hospital and University Center, Coimbra, Portugal
Background: Changes involving the descending pathways that modulate pain signal have been
highlighted as a possible mechanism in chronic pain syndromes. Endogenous opioids, noradrenaline
and serotonine are the main neurotransmitters involved. Such findings support the use of
antidepressants as therapeutic adjuncts in chronic pain. The most common antidepressants used to
alleviate chronic pain include: tricyclic (TCAs), serotonin and norepinephrine reuptake inhibitors
(SNRIs), selective serotonin reuptake inhibitors (SSRIs) and novel antidepressants like bupropion or
mirtazapine.
Aims: Since May 2011, the Unit of Consultation-Liaison Psychiatry provides consultation to patients
with chronic pain conditions in the Pain Unit of the Hospital and University Center of Coimbra. The
authors aimed to do a retrospective study of the psychopharmacological interventions selected, and
make a correlation between the psychiatric diagnosis, the kind of chronic pain condition presented
and the selected antidepressant drugs.
Methods: All patients were assessed using the Brief Pain Inventory (Short Form); psychiatric
th
diagnoses were made according to the International Classification of Diseases (ICD) - 10 revision.
Data were analyzed using SPSS20.0 to execute descriptive statistics.
Results: 98 patients with chronic pain were referred to psychiatric assessment (n=98). About half of
the patients had “centralized” pain syndromes (most fibromyalgia) and almost two thirds had a mood
disorder (major depressive episode or distimic disorder). TCAs were the most used antidepressant
(70%), followed by SNRI (60%) and SSRIs (30%).
Conclusions: Our results are according to the international literature, concerning the preferential use
of TCAs to treat both psychiatric and chronic pain conditions.
440
ACTIVATION OF DESCENDING INHIBITORY SYSTEM MAY PREVENT CHRONIC PAIN
RELATED DEPRESSION: POSSIBLE INTERACTION BETWEEN 5-HT AND BRAIN-DERIVED
NEUROTROPHIC FACTOR
1
2
3
4
T. Ishikawa , S. Yasuda , K. Ishikawa , T. Kakeda , M. Yanagihara
1
2
2
3
Department of Neursciences, Yamaguchi University, Yamaguchi, Sapporo Medical Univerisity,
4
Sapporo, Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki, Japan
Aims: Chronic pain with depression results in a serious determinant that negatively affects QOL.
Recent brain imaging in chronic pain demonstrated the activation of limbic system (called “painemotion”). Affective state related to low BDNF may lead to dysfunction of descending inhibitory
systems. Imipramine (IMI) is widely used for reducing depression by activating 5-HTergic neuron, but
little is known whether IMI interacts with BDNF in CNS. Thus, we characterized trkB-related signaling
(pERK, BDNF mRNA) in depression related to chronic pain comparing with magnetic stimulation (MS)
which evokes spinal 5-HT release.
Methods: Sprague-Dawley rats were subjected to chronic constriction injury (CCI). We employed
Plantar testing (hyperalgesia:PWL) and a forced swimming test (depression). We measured the
signaling (pERK1/2 immunoreactivity) and the BDNF mRNA (RT-PCR). IMI was administered i.p. to
reduce depression after CCI. To ensure anti-depressant effects, anti-BDNF, K252a (TrkB receptor
agonist) was injected i.c.v.
Results: During chronic pain, the rats showed a sustained decrease in PWL associated with
extended immobility time and an increase of pERK1/2 and a decrease of BDNF mRNA in CNS. Antidepressant effect of IMI were reversed by anti-BDNF, K252a, and 5, 7-DHT. The increase of BDNF
mRNA with IMI was antagonized by DHT. Moreover, MS ameliorates depression and was
antagonized by anti-BDNF or K252a. MS activated descending inhibitory system via increased spinal
5-HT release.
Conclusion: These data clearly demonstrated that IMI reduce depression in chronic pain via.
preventing abnormal trkB related signals(ERK1/2) and BDNF synthesis, suggesting IMI modulates
synaptic transmission by interacting with BDNF in pain-emotion state.
441
THE ANTIGLUTAMATE MECHANISMS OF ANALGESIC AND ANTIPRURITIC ACTION OF SOME
ANTIDEPRESSANTS
1
1
1
1
1
N. Shestakova , D. Belinskaya , D. Tikhonov , O. Barygin , E. Nagaeva , N. Vanchakova
2
1
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences,
State Pavlov Medical University, Saint Petersburg, Russia
2
Background and aims: Earlier we obtained the V-like aromatic group in antidepressant molecule
structure which were effective for management of itch and pain syndromes. Independently we
revealed the same group was important for NMDA blockers. The aim was to check the hypothesis on
antiglutamate mechanisms of analgesic and antipruritic action of antidepressants.
Methods: Electrophysiological measurement of antidepressant acting on the ionic currents through
NMDA and AMPA channels in rat brain neurons by methods of membrane potential fixation in the
whole cell configuration.
Results: None of the compounds showed significant blocking ability against AMPA receptors in
physiologically reasonable concentrations. On the contrary, desipramine, chlorpromazine,
amitriptyline block voltage-dependently NMDA receptors by the mechanism of the trap. IC50 values
(concentration causing the reduction of response to 50%) for these compounds are equal to 1.57 ±
0.13 mM; 4.3 ± 1.0 mM; 14.1 ± 0.7 mM, respectively. Analysis of 3D models of desipramine,
chlorpromazine and amitriptyline has showed that the structure of these compounds or their
metabolites has V-like group formed by aromatic rings. Aromatic groups of clozapine, methiothepine
and fluoxetine have other configurations. Their blocking efficiency is much lower: IC50 value of the
voltage-independent blocking are equal to 36.2 ± 1.7 mM (fluoxetine); 70 ± 10 mM (clozapine);
methiothepin blocks the receptor voltage-dependently weakly. Desipramine, chlorpromazine and
amitriptyline are effective for the management of pain and itch syndromes; clozapine, methiothepine
and fluoxetine are not.
Conclusion: NMDA receptor blocking is the common element for analgesic and antipruritic
mechanisms of antidepressants.
Supported by RFBR №12-04-00454-а.
442
AGOMELATINE IMPROVES VISCERAL AND NEUROPATHIC PAIN IN RATS
1
2
3
D. Zurowski , J. Wordliczek , J. Dobrogowski , P. Thor
1
2
1
3
Department of Pathophysiology, Department of Pain Treatment and Palliative Care, Department of
Pain Research and Treatment, Jagiellonian University Medical College, Cracow, Poland
Background and aims: Agomelatine is a novel clinically effective antidepressant drug with
melatonergic (MT1/MT2) agonist and 5-HT2C receptor antagonist properties. We aimed to determine
if agomelatine was effective in models of visceral and neuropathic pain.
Methods: The study was carried out on male Wistar rats divided into four groups. In first and second
group peritonitis was induced by i.p. acetic acid injection. In second group agomelatine (20, 40, 60
mg/kg) was given i.p. before acetic acid administration. The intensity of nociception was quantified by
counting the number of writhes for 30 min after acetic acid injection. We also investigated the effect of
agomelatine on mechanical allodynia observed in neuropathic pain rat model prepared by chronic
constriction injury (CCI) of the right sciatic nerve in third group. Group four was sham operated and
served as control. After 2 weeks mechanical hypersensitivity using von Frey test was evaluated.
Results: Intraperitoneal administration of acetic acid induced nociceptive writhing response (WR) in
rats. Agomelatine dose-dependly reversed visceral hyperalgesia and showed an analgesic effect (p<
0,01). We observed mechanical allodynia in CCI rats and agomelatine increases the mechanical
nociceptive threshold in neuropathic pain model (p< 0.05).
Conclusions: Our results indicate that agomelatine increase mechanical nociceptive threshold
showing antiallodynic effect and improves visceral pain. Accordingly, our data represent a new
interesting therapeutic modality for the pain relief.
443
A FURTHER INVESTIGATION ON THE ANTINOCICEPTIVE PROFILE OF AM94, A
FLUORINATED BIPHALIN ANALOGUE WITH NON‐HYDRAZINE LINKER
1
2
3
1
A. Di Giannuario , A. Mollica , R. Costante , S. Pieretti
1
Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome,
3
Department of Pharmacy, University of Chieti-Pescara, Chieti, Department of Pharmacy, University
of Chieti-Pescara, Rome, Italy
2
Background and aims: The opioid Biphalin (Tyr-D-Ala-Gly-Phe-NH)2, shows a high potency with a
nearly equal affinity for µ- and δ-opioid receptors in nanomolar range and a lower affinity for κreceptor. Following intracerebroventricular (i.c.v.) or intrathecal administration, biphalin is at least 200fold more potent than morphine in eliciting antinociception. Biphalin administered subcutaneously
(s.c.) showed negligible antinociceptive activity, but when given intravenously (i.v.) produced
significant analgesia although less potent than morphine via this route. These results indicated that
biphalin has intrinsic activity that is compromised by enzymatic degradation. Recently, the synthesis
was reported of a new biphalin analogue namely AM94 [(Tyr-D-Ala-Gly-pFPhe)2piperazine] that
showed µ- and δ-opioid affinity at least 10-fold higher than biphalin and a greater antinociceptive
effect than biphalin, following both i.c.v and i.v. administration (Mollica et al., J. Pep.Sci. 2013, in
press). In this study, the antinociceptive effects of AM94 was further evaluated in an inflammatory
pain model after s.c. administration in mice.
Methods: Male CD-1 mice were used in the experiments. AM94 effects were evaluated after s.c.
administration in the formalin test.
Results: AM94 showed a higher antinociceptive effect respect to biphalin in both phases of the test,
probably due to a better enzymatic stability of AM94. The activity of AM94 was comparable with that
of morphine.
Conclusions: These results indicated an increased metabolic stability of AM94 compared to biphalin,
with a consequent prolongation of the antinociceptive response also after s.c. administration and
confirmed the importance of mixed µ/δ agonists as a future alternative in treatment of severe pain.
444
BLOCKADE OF GLUTAMATE RELEASE BY BOTULINUM NEUROTOXIN TYPE A IN A HUMAN
EXPERIMENTAL PAIN MODEL: A DERMAL MICRODIALYSIS STUDY
1
2
3
2
1
L. Bittencourt da Silva , A. Karshenas , S. Rasmussen , F.W. Bach , L. Arendt-Nielsen , P. Gazerani
1
1
Center for Sensory - Motor Interaction (SMI), Department of Health Science and Technology,
2
3
Aalborg University, Department of Neurology, Orthopaedic Surgery Research Unit, Aalborg
University Hospital, Aalborg, Denmark
Background and aims: Analgesic action of Botulinum neurotoxin type A (BoNTA) has been linked to
blockade of peripheral release of neuropeptides and neurotransmitters but this has not yet been
investigated in humans. The present dermal microdialysis study was designed to investigate the
BoNTA effect on glutamate release in a human experimental model of pain and sensitization
provoked by capsaicin plus mild heat.
Methods: Twelve healthy volunteers (6 males) were pre-treated with intradermal BoNTA (10U) on
one volar forearm with saline control on the contralateral side. Dermal microdialysis was applied 1
week later to collect interstitial samples before and after capsaicin patch (8%) application plus mild
heat stimulation (40°C for 60min). Samples were collected every hour for 3h through linear
microdialysis probes (10mm, 100kDa). Dialysate was analyzed for glutamate levels. Pain scores
(rated on VAS) and skin vasomotor reactions (captured by thermocamera and laser speckle) were
recorded to assess pain and neurogenic inflammation provoked by capsaicin+heat model.
Results: BoNTA significantly reduced capsaicin+heat-evoked glutamate release in comparison with
saline (P< 0.05). Provoked pain intensity was lower in BoNTA pre-treated arm (P< 0.01). Cutaneous
blood flow was significantly reduced by BoNTA (P< 0.05) but not cutaneous temperature (P≥0.05).
There was a correlation between glutamate level and blood flow (r=0.58/P< 0.05) but not for
temperature (P≥0.05). The BoNTA effect was not gender-dependent.
Conclusions: BoNTA reduced release of glutamate in human skin when it was provoked by
capsaicin+heat stimulation. However, reduction of pain scores by BoNTA was not correlated with the
level of glutamate.
445
NONPEPTIDE PKR ANTAGONIST IN AN ANIMAL MODEL OF NEUROPATHIC PAIN
1
1
1
1
1
2
1
A. Cappiello , R. Lattanzi , D. Maftei , L.A. Giancotti , V. Marconi , F. Florenzano , L. Negri
1
2
Physiology and Pharmacology 'Vittorio Erspamer', Sapienza, EBRI, Rita Levi-Montalcini Foundation,
Roma, Italy
Background: PK2, or mammalian Bv8, belongs to a new family of pronociceptive chemokines which
can lower pain threshold and modulate immune responses, through two G-protein coupled receptors:
PKR1, mainly distributed in the peripheral nervous system, and PKR2, highly expressed throughout
the brain. In an animal model of CFA-induced paw inflammation, we brought evidence that the
granulocyte-derived Bv8/PK2 is a major determinant in triggering inflammatory pain and blocking the
PKRs is a winning strategy to abrogate hypernociception. We synthesized a non-peptide molecule,
PC1 (a PKR1-preferring ligand) which selectively antagonizes Bv8-induced hyperalgesia and is highly
effective in inflammatory pain treatment.
Aim: We evaluated the effectiveness of PC1 in a mouse model of neuropathic pain, chronic
constriction injury (CCI), which combines nerve compression with an epineural inflammation.
Methods: Thermal hyperalgesia (Plantar test), mechanical (Dynamic Aestesiomether) and tactile
allodynia (Von Frey filaments) were assessed. PC1 was injected at 150 µg/kg dose s.c. twice a day,
from days 3-9.
Results: All mice developed thermal hyperalgesia and mechanical allodynia from day 1 and tactile
allodynia from day 12 after surgery, on the lesion side, while sham-operated mice did not. Acute
administration of PC1 abolished CCI-induced thermal hyperalgesia and tactile allodynia for »2h.
Repeated administrations of PC1 significantly reduced the development of thermal hyperalgesia and
mechanical allodynia and prevented development of tactile allodynia.
Spinal cord immunohistochemistry showed an increase of PK2-levels 10-days after CCI-induction.
PC1-treatment decreased both PK2-levels and CCI-induced microglia activation.
Conclusion: In conclusion, the PKR-blocking might be a successful strategy in preventing/reducing
neuropathic pain.
446
PHARMACOLOGICAL EFFECTS OF PROKINETICIN RECEPTORS ANTAGONIST
1
1
1
1
1
2
2
L.A. Giancotti , R. Lattanzi , D. Maftei , V. Marconi , A. Cappiello , R. Romano , S. Maione , L. Negri
1
1
Department of Physiology and Phramacology 'V. Erspamer', Sapienza, University of Rome, Roma,
Department of Experimental Medicine, Phamacology Division, The Second University of Naples,
Naples, Italy
2
Background and aims: Bv8, Prokineticin 1 (PK1 or EG-VEGF) and Prokineticin 2 (PK2 or
mammalian-Bv8) make up a new family of chemokines involved in different biological activity such as:
circadian rhythms, neurogenesis, angiogenesis, haematopoiesis and pain sensitization. These
chemokines activate two G-protein linked receptors [prokineticin receptors 1 (PKR1) and prokineticin
receptors 2 (PKR2)] distributed in mammalian tissues: PKR1 is more widely distributed in the
periphery and PKR2 is highly expressed throughout the central nervous system. A triazine derivative
compound, named PC1, recently designed and synthesized demonstrated to be a PKRs antagonist.In
vitro, binding experiments indicated that PC1 is a PKR1 preferring ligand with an affinity 30 times
higher for PKR1 than for PKR2.
Methods and results: PC1 is able to antagonize hyperalgesia induced by intra-paw injection of Bv8
(0.5 ng i.pl.) both by topical administration (10 ng i.pl.) and by systemic administration (15 µg/kg
s.c.).PC1 is also effective in a model of inflammatory pain: 150 µg/kg dose abolished thermal-induced
pain, reduced paw oedema and speeds-up paw healing. We also tested the standard dose of PC1
(150 µg/kg) in naïve animals in different paradigms:


PC1 increased basal pain threshold, decreased capsaicin-induced licking and decreased acid
acetic-induced whrithing;
In paradigms involving PKRs in brain, PC1 showed an anxiolytic and antidepressant effect
and it had no effect on motor and memory activity, and on obsessive-compulsive behavior.
Conclusions: These data demonstrate that PKRs may represent a therapeutic target for the
development of not only novel antinociceptive drugs but also of anxiolityc and antidepressant drugs.
447
ARACHIDONYLCYCLOPROPYLAMIDE, A CANNABINOID 1 RECEPTOR AGONIST
ATTENUATED POSTINCISIONAL PAIN IN RATS FOLLOWING LOCAL ADMINISTRATION
S. Basu Ray, M. Gautam, A. Singh, P. Prasoon, R. Kumar
Anatomy, All India Institute of Medical Sciences, Delhi, India
Background: Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and local anaesthetics
into the surgical site relieves postoperative pain. However, to the best of knowledge, a preclinical
animal model for evaluating the efficacy of such drugs is lacking. The aim of the study was to
standardize local drug administration in the plantar incision model and thereafter compare the
analgesic efficacy of flurbiprofen, an NSAID to a novel cannabinoid 1 receptor agonist,
arachidonylcyclopropylamide (ACPA). Finally, these were compared to lignocaine (LA), a local
anaesthetic agent.
Methods: All drugs were administered locally into the wound in 10 µl volume by a micropipette once
during surgery. Postincisional pain was evaluated by guarding behaviour, thermal hyperalgesia and
mechanical allodynia. The role of cannabinoid 1 receptors (CB1R) was determined by preadministration of AM251 during surgery. Analgesic effect of flurbiprofen (30µg) was compared to
ACPA (30 and 100 µg) and lignocaine (30 µg) (until day 1). Cyclo-oxygenase (COX) enzyme activity
was assayed in incised area. Locomotor activity after ACPA administration was also studied.
Results: Flurbiprofen (3, 10 and 30µg) could relieve guarding at 2 h in a dose-dependent manner.
ACPA produced a higher analgesic effect and attenuated both guarding and thermal hyperalgesia to
basal levels by days 2 and 3 respectively. Analgesic effect of ACPA but not flurbiprofen was reversed
by AM251. Possibly, flurbiprofen inhibited COX 1 activity. Locomotor activity also increased after
ACPA. Lignocaine did not show any analgesic effect.
Conclusion: Local administration during plantar incision could help identify novel analgesic drugs like
ACPA.
448
THE ROLE OF ENDOCANNABINOID SYSTEM IN THE ANTIPRURITIC EFFECT OF SYSTEMIC
PARACETAMOL
G. Saglam, O. Gunduz, A. Ulugol
Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Edirne, Turkey
Background and aims: Cannabinoid CB1 receptors have been shown to play role in the
antinociceptive action of paracetamol. Since itch and pain sensations share many similarities, the
purpose of the present study was to investigate whether blockade of cannabinoid CB1 and CB2
receptors participate the antipruritic activity of paracetamol in mice.
Methods: Scratching behavior was induced by intradermal injection of 50 µg/50 µL of serotonin into
the rostral part of the back of the mice. After serotonin administration, scratching of the injected site by
the hind-paws were videotaped and counted for 30 min.
Results: Paracetamol attenuated serotonin-induced scratching at the highest dose used (300 mg/kg).
The CB1 receptor antagonist, AM-251 (1 mg/kg), and the CB2 receptor antagonist, SR-144528 (1
mg/kg), at doses that had no effect on their own, did not alter the antiscratching behavior activity of
paracetamol.
Conclusions: Our results indicate that, in contrast to its antinociceptive action, cannabinoid receptors
are not involved in the antipruritic effect of paracetamol.
Acknowledgements: This work was supported by a grant from Trakya University Research Council
(TUBAP-2012/186). The authors have no conflicts of interests to report.
449
HYPERALGESIC WISTAR-KYOTO RATS EXHIBIT REDUCED CB1 RECEPTOR EXPRESSION
AND IMPAIRED CB1 RECEPTOR AGONIST-INDUCED ANTINOCICEPTION IN THE LATERAL
PERIAQUEDUCTAL GREY
1,2
1,2
1,2
1,2
1
2,3
1,2
E.M. Jennings , W.M. Olango , K. Rea , B. Okine , F. McGowan , M. Roche , D.P. Finn
1
2
Department of Pharmacology, NCBES Centre for Pain Research and Galway Neuroscience Centre,
Department of Physiology, National University of Ireland, Galway, Ireland
3
Background and aims: Wistar-Kyoto (WKY) rats display hyper-responsitiy to stress and enhanced
nociceptive responding compared with Sprague-Dawley (SD) rats. The endocannabinoid system
plays an important role in stress-induced hyperalgesia. The aim of this study was to investigate
whether altered expression and/or functionality of CB1 receptors in the periaqueductal grey (PAG)
underlie hyperalgesia to formalin injection in WKY versus SD rats.
Methods: Adult male SD and WKY rats (250-350g; n=6-12 per group) were used. Tissue levels of
endocannabinoids and cannabinoid CB1 receptor mRNA in the PAG were measured by LC-MS-MS
and qRT-PCR, respectively. Another cohort of SD and WKY rats received bilateral microinjection of
vehicle or CB1 receptor agonist, arachidonyl-2-chloroethylamide (ACEA; 0.05 pmol), into the lateral
PAG (lPAG) and formalin-evoked nociceptive behaviour was assessed. Data were analysed by
ANOVA and Fisher's LSD (P< 0.05 significant).
Results: WKY rats exhibited greater formalin-evoked nociceptive behaviour than SD rats. WKY rats
had lower levels of CB1 receptor mRNA and increased levels of 2-arachidonoyl glycerol in the lPAG,
versus SD. Intra-lPAG administration of ACEA reduced formalin-evoked nociceptive behaviour in SD,
but not WKY, rats. ACEA administration to WKY potentiated nociceptive behaviour towards the end of
the formalin trial.
Conclusions: These data suggest that activation of CB1 receptors in the lPAG of SD, but not WKY,
reduces formalin-evoked nociceptive behaviour. In addition, enhanced formalin-evoked responding in
WKY rats is associated with lower expression of the CB1 receptor and increased tissue levels of the
endocannabinoid, 2-arachidonoyl glycerol, in the lPAG.
Acknowledgements: Science Foundation Ireland (10/IN.1/B2976) and IRCSET.
450
INVOLVEMENT OF CANNABINOID CB1 RECEPTORS IN THE ANTINOCICEPTIVE EFFECT OF
DIPYRONE
P. Elmas, A. Ulugol
Department of Medical Pharmacology, Trakya University, Faculty of Medicine, Edirne, Turkey
Background and aims: Cannabinoid CB1 receptors have been implicated in the antinociceptive
effect of paracetamol. In the current study, we examined whether blockade of CB1 receptors prevent
the analgesic activity of dipyrone, in a similar way to paracetamol.
Methods: Hot-plate and tail-flick tests were used to assess the antinociceptive activity in mice.
Results: Dipyrone and WIN 55,212-2, a cannabinoid agonist, exerted significant antinociceptive
effects in both hot plate and tail flick tests. The CB1 receptor antagonist, AM-251 (3 mg/kg), at a dose
which had no effect when used alone, did not alter the antinociceptive effect of dipyrone, whereas
completely prevented the antinociceptive activity of WIN 55,212-2 in both thermal antinociception
tests.
Conclusions: Our findings suggest, unlike paracetamol, that cannabinoid CB1 receptors do not
participate in the antinociceptive action of dipyrone under non-inflammatory and non-neuropathic
states.
Acknowledgements: This work was supported by a grant from Trakya University Research Council
(TUBAP-2012/58). The authors have no conflicts of interests to report.
451
EFFECT OF WARMING AND BUFFERING OF THE INFILTRATED LIDOCAINE ON PAIN
EXPERIENCED DURING THE VARIOUS STEPS OF BONE MARROW SAMPLING
1
2
A.-M. Kuivalainen , F. Ebeling , P.H. Rosenberg
3
1
Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital,
2
3
Vantaa, Department of Haematology, Helsinki University Central Hospital, Department of
Anaesthesiology and Intensive Care Medicine, University of Helsinki, Helsinki, Finland
Background and aims: Overall pain experienced during bone marrow aspiration or biopsy (BMAB)
may depend on both human and procedural factors. Buffering the acidic local anaesthetic solution
may reduce infiltration pain and warming further facilitates this effect (Yang et al. 2006). We compared
the pain experiences during BMAB when infiltration anaesthesia was provided with warmed buffered
lidocaine or room temperature unbuffered lidocaine.
Methods: After taking pain history and scoring preprocedural anxiety (NRS, Numeral Rating Scale, 010) one hundred adults scheduled for BMAB received warmed (32˚C) lidocaine 20 mg/ml with
adrenaline buffered with sodium bicarbonate, pH 7.3 (n=50), or room temperature (22°C) unbuffered
lidocaine 20 mg/ml with adrenaline, pH 3.7 (n=50) in a random and patient blinded fashion, two
minutes before the bone marrow puncture. The patients scored their pain experience (NRS) during
infiltration, puncture, aspiration and biopsy.
Results: Pain during infiltration with warm and buffered lidocaine was less intense than that with
unmodified solution (median NRS 2.0 vs. 4.0, p< 0.002). Previous encounter of pain from dental or
surgical procedures correlated with present local anaesthetic infiltration pain. The other BMAB phases
were equally painful in both groups. Anxiety was a strong predictor of procedural pain.
Conclusions: Warming and buffering the local anaethetic make the infiltration pain less intense but
does not affect the subsequent painful phases of BMAB. Pain during BMAB can be predicted by
assessing preprocedural anxiety.
Yang et al. Warm and neutral tumescent anesthetic solutions are essential factors for a less painful
injection. Dermatol Surg 2006; 32(9):1119-23.
452
ASPIRATION STUDY AFTER ADMINISTRATION OF A NEW BUPIVACAINE LOZENGE TO
HEALTHY SUBJECTS AND HEAD/NECK CANCER PATIENTS WITH ORAL MUCOSITIS
1,2
1,2
1,2
3
4
1,2
S. Mogensen , K. Sveinsdottir , C. Treldal , M. Rasmussen , J. Jacobsen , J. Petersen , A.
5
5
1,2
Mohammad , A. Nygård , O. Andersen
1
2
Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Hvidovre, Clinical Research
3
4
Centre, Copenhagen University Hospital, Amager, Amager, None, Department of Pharmacy, School
5
of Pharmaceutical Sciences, University of Copenhagen, Department of Radiology, Copenhagen
University Hospital, Rigshospitalet, Copenhagen, Denmark
Background and aims: Oral mucositis induces server oral pain and is a serious complication to
cancer treatment. Close to 100% of patients undergoing high-dose chemotherapy or radiation
treatment for head and neck cancer will develop oral mucositis. There is currently no sufficient pain
management for oral mucositis pain. Therefore a new lozenge containing 25mg bupivacaine as a
local oromucosal and pharynx anesthesia is tested. The purpose of pain management with this
lozenge is to maintain and improve the patient´s nutritional status by anesthetizing the oral cavity
before meals.
It has previously been assumed that there is a risk of aspiration after pharyngeal anesthesia and that
it affects the self-regulating swallowing reflex.
Therefore the risk of aspiration after administration of bupivacaine lozenges to healthy subjects with
normal mucosa and to patients with oral mucositis was studied.
Methods: The risk of aspiration was studied before and after a single dose 25mg bupivacaine
lozenge to 10 healthy subjects and 10 patients. The patients swallowed 20ml barium-contrast agent
and its path through the oesophagus was recorded using video radiography. The videos were
analysed for aspiration.
Results: There were no signs of aspiration in the 10 healthy subjects after administration of a
bupivacaine lozenge. Currently one oral mucositis patient is included. This patient showed no signs of
aspiration.
Conclusion: The preliminary results indicate that the bupivacaine lozenge is safe as pain
management before food and drink consumption for patients with oral mucositis. The study will be
completed in July 2013.
453
SYSTEMIC PHARMACOKINETICTS OF BUPIVACAINE FROM NEW LOZENGE IN HEALTHY
SUBJECTS AND HEAD & NECK CANCER PATIENTS WITH ORAL MUCOSITIS
1
1
1
1
1
2
S. Mogensen , K. Sveinsdottir , C. Treldal , O. Andersen , J. Petersen , M. Rasmussen , J.
3
4
Jacobsen , M. Kreilgaard
1
2
Clinical Research Centre, Copenhagen University Hospital, Hvidovre and Amager, Hvidovre, None,
4
Department of Pharmacy, Department of Drug Design and Pharmacology, School of Pharmaceutical
Sciences, University of Copenhagen, Copenhagen, Denmark
3
Background and aim: Oral mucositis is serious complication to cancer treatment. Close to 100% of
patients undergoing high-dose chemotherapy or radiation treatment for head and neck cancer will
develop oral mucositis, which induces server oromucoal and pharynx pain. There is currently no
sufficient pain management for oral mucositis pain.
The research group has developed a new bupivacaine lozenge as local anesthetic of the mouth and
pharynx. Bupivacaine has not been used as local oral administration before. Therefore it is important
to study the side effects and plasma concentrations after the topical oromucsal administration of the
bupivacaine lozenge to healthy subject and patient with oral mucositis.
Methods: Baseline blood sample was drawn before administration of a bupivacaine lozenge as single
dose of 25mg and followed by blood samples ongoing for 6 hours on 10 healthy subjects and 3 hours
on 10 patients. The bupivacaine serum concentration is measured by LC/MS/MS. The individual
pharmacokinetics parameters were estimated by a two-compartment model with absorption lag-time
using Phoenix WinNonlin 63.
Results: The healthy subjects had a maximum plasma concentration of 376 ng/ml of bupivacaine
after single dose administration of the lozenge.
The samples from patients will be analysed in June 2013, but preliminary analyses show that the
absorption is similar to healthy subjects.
Conclusion: The preliminary results indicate that the use of a 25 mg bupivacaine lozenge is safe to
use as pain management in oral mucositis as maximum serum concentrations were at least 6-fold
below tolerable level (2-4 mg/ml).
454
LONG TERM THERAPY WITH THERAPEUTIC LOCAL ANALGESIA FOR THE TREATMENT OF
CHRONIC THERAPY RESISTANT COMPLAINTS IN COMBINATION WITH ACUPUNCTURE
ANALGESIA
1
2
3
4
5
6
7
T. Nguyen , H. Eckel , A. Argyrakis , K. Saupp , C. Pohl , S.H. Liem , W. Vogelsberger , T.T.
8
Nguyen
1
2
3
Praxis, Radiology Institute at the Protestant Hospital, Göttingen, Neurologist, Bad Karlshafen,
Anaesthesia Department and Treatment Department of Chronic Pain-Sick Persons, Protestant
5
Hospital in the Hospital Community of the Church Circle, Herne, Specialist for General Medicine,
6
Nature Treatments and Particular Pain Therapy, Bochum, Specialist for Anaesthesiology, Berlin,
7
8
Specialist for Anaesthesiology, Naturopathic, Freiburg, Childrens Clinic at the University Clinic,
Göttingen, Germany
4
For pain patients who have exhausted all treatment options, it is psychologically difficult for them to
cope with the situation when the doctors tell them they cannot be helped. They fall into social isolation
because the unbearable pain does not allow them to participate in the society.
With anaesthetic-saving and painless and until now side-effect-free therapeutical local analgesia and
acupuncture analgesia according to Trang, the pain could be almost completely eliminated.
After repeated treatment, the patients have a tolerable pain intensity. When the degeneration of the
spine or organs is very strong, the pain reduction can be achieved in about 8 to 12 treatments to
almost about 100%, that in the beginning after the treatment held for a couple of hours to a few days.
After successive treatments, the pain relief lasted for about 3 to 4 weeks so that the patients could
lead a normal pain-free quality of life with long-term treatment intervals of every 4 to 8 weeks. If
necessary, all normal pain medications can also be prescribed. Patients who have been treated for
over 25 years with this long term therapy every 4 to 8 weeks have received no side effects
whatsoever from Procaine and Licain.
The combination therapy from Trang is the last hope for patients with untreatable complaints who
have received no relief elsewhere. The patients remain partially capable of working and the costs for
inpatient treatment are not incurred. Thus the high health insurance and pension insurance costs are
spared.
455
EFFECTIVENESS OF THERAPEUTIC ULTRASOUND COMPARED WITH NON-STEROIDAL ANTI
INFLAMMATORY DRUGS (NSAID) FOR LATERAL EPICONDYLITIS: A RANDOMIZED
CONTROLLED TRIAL
1
2
3
1
N. Abazi , A. Nevzati , Z. Ibraimi , A. Murtezani , V. Hysenaj
1
1
2
University Clinical Center of Kosovo, Prishtina, Kosovo, Physiotherapy and Occupational Therapy,
3
University Hospital Zurich, Zurich, Switzerland, Faculty of Medicine, Prishtina, Kosovo
Introduction: Lateral elbow tendinopathy (tennis elbow, TE), is a musculoskeletal disorder that can
cause significant pain and disability. The common practice for treatment of TE is conservative
treatment with rest and anti-inflammatory medication and corticosteroids. Physiotherapy including
ultrasound has been claimed to have better effect.
Aim: To compare the effectiveness of therapeutic ultrasound with NSAIDs for the treatment of lateral
epicondylitis.
Methods: Randomized controlled trial of random allocation of subjects to either a drug group (n=32)
or a physiotherapeutic intervention group (n=34) was performed. Participants aged at least 18 years
with a clinical diagnosis of TE, characterized by lateral elbow pain were included. The diagnosis was
based on a history of lateral elbow pain exacerbated by gripping activities and tenderness at the
lateral epicondyle coupled with lateral elbow pain. The Patient-rated Tennis Elbow Evaluation
(PRTEE) was used for these disorders. It takes the form of a 15-item questionnaire, with five items
addressing pain and 10 concerned with functional deficit. Both groups were treated for 12 weeks.
Results: Sixty-six subjects aged 18-80 were recruited over a 6-month period. In the active group 74%
(17/29) achieved at least 60% improvement from baseline in elbow pain at 12 weeks compared with
47% (11/22) in the drugs group (difference of 27%; 95% confidence interval 220 to 35%).
Conclusion: Overall, the findings indicated that corticosteroid injections are effective at short-term
follow-up, and ultrasound interventions are effective at intermediate- and long-term follow-up. Our
results suggest that ultrasound therapy is beneficial in the treatment of TE.
456
PARECOXIB DECREASES KIDNEY INJURY ON THE RENAL ISCHEMIA-REPERFUSION
STRESS MODEL. EXPERIMENTAL STUDY IN RATS USING NGAL AS RENAL FUNCTION
BIOMARKER
1
1
1
2
1
J.P. Calistro Neto , R.D.C. Torres , G.M. Gonçalves , L.M. Silva , N.S.P. Módolo , G.A.M. Barros
1
1
Anesthesiology, Botucatu Medical School - UNESP - Univ. Estadual Paulista, Botucatu,
Anesthesiology, Hospital São Luís - Rede Dòr, São Paulo, Brazil
2
Background and aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) have proved their efficacy, in
a multidimensional approach, on reducing the opioid consumption during the postoperative acute
pain. Although the NSAIDs may affect the renal function, there are few data as to the use of coxibs.
The early biomarkers of acute renal injury (EBARI) may be important in determining the actual risk
associated with the use of coxibs NSAIDs in the perioperative period.
Methods: After approval by Experimental Ethics Committee, 40 male Wistar rats were randomly
assigned into four groups. Under general anesthesia, and depending on the assigned group, rats
underwent renal ischemia-reperfusion. Parecoxib was injected in two of the groups to evaluate the
coxib intluence on renal function. Parametric data, serum neutrophil gelatinase-associated lipocalin
(NGAL), an EBARI, and right and left renal histology were obtained in four different moments.
Results: The ischemia group which did not receive parecoxib showed the highest NGAL level
(Table, *p = 0.001), as well as the most severe tubular injury. The ischemia group which received
injection of parecoxib showed NGAL levels and tubular injury similar to the groups not subjected to
renal ischemia.
Group
M1 (carotid
catheterization)
M2 (5´ after renal
ischemia)
M3 (20´ after renal M4 (2h after
reperfusion)
anesthesia)
Ischemia
15.23 ±6.40
32.43 ±35.52
37.54 ±38.64
1186.63 ±1574.77*
Parecoxib
11.72 2±5.45
10.68 ±5.70
12.63 ±5.48
254.56 ±103.69
Sham
12.44 ±5.51
23.51 ±34.86
15.99 ±5.21
311.05 ±163,20
Control
11.80 ±3.42
10.02 ±2.91
12.84.±2.55
296.63 ±78.37
[NGAL on four different moments of the experiment.]
Conclusion: On this experimental model, parecoxib showed protective renal properties.
457
DIFFERENCES BETWEEN ORAL AND INTRA-ARTICULAR DEXKETOPROFEN AND TRAMADOL
IN KNEE JOINT OSTEOARTHRITIS PAIN INDUCED BY MONOSODIUM IODOACETATE IN RATS
C. Cialdai, S. Giuliani, C. Valenti, M. Tramontana, C.A. Maggi
Pharmacology Department, Menarini Ricerche S.p.A., Florence, Italy
Background and aims: Pharmacological treatments of osteoarthritis aim to reduce pain in order to
improve the patient joint function and quality of life.
This study compared the effect of oral or intra-articular (i.ar.) administration of dexketoprofen and
tramadol, alone or in combination, on the knee osteoarthritis pain induced by monosodium
iodoacetate (MIA) in the rat.
Methods: MIA (1 mg/25 µl) was administered intra-articularly in the right knee while the left knee
received saline (25 µl) and seven days later the drugs or the vehicle were administered. Nociception
was evaluated as alterations in hind limb weight distribution with Incapacitance tester (Linton
Instrumentation, Norfolk, UK).
Results: Oral dexketoprofen (0.1-1 mg/kg) or tramadol (0.5-5 mg/kg) induced antinociception at 1 and
5 mg/kg, respectively. Their combination (0.5+2.5 mg/kg) induced an additive increase of the intensity
and duration of antinociception.
The intra-articular administration of dexketoprofen or tramadol (10-100 µg/25 µl) inhibited MIAinduced pain at the higher doses. Combining the drugs at the lower doses (10 µg/25 µl) a more than
additive long lasting antinociceptive effect was measured indicating synergism. This effect was
significantly reduced by naloxone (10 µg/25 µl, i.ar.) co-administered with both drugs. Intra-articular
dexketoprofen plus tramadol (10 µg/25 µl) in the contralateral control knee joint still produced a
marked synergistic antinociceptive effect indicating a significant systemic diffusion.
Conclusions: The additive or synergistic antinociceptive effects produced by the combined oral or
intra-articular administration, respectively, of dexketoprofen and tramadol, might allow to get
therapeutic advantages with low side effects.
458
A NEW PHARMACEUTICAL FORM OF PARACETAMOL: EFFICACY OF TRANSMUCOUS
BUCCAL PARACETAMOL IN ACUTE PAIN PATIENTS
1
2
3
3
3
G. Pickering , F. Moustafa , D. Roux , N. Macian , C. Dubray , J. Schmidt
1
2
2
3
Clinical Pharmacology, CIC, CHU Clermont-Ferrand, A and E Department, CHU, CIC, CHU
Clermont-Ferrand, Clermont-Ferrand, France
Background: Oral or intra-venous (iv) paracetamol (APAP) has a latency to be effective. When fast
relief is required or oral/iv routes are not available, transmucosal buccal(b) route may be an
alternative. A new pharmaceutical form of bAPAP is studied in patients admitted to hospital for acute
pain.
Methods: A randomized double-blind trial (NCT01586143) included 38 patients admitted to the
Accident and Emergency Department of Clermont-Fd University Hospital, France, for upper or lower
limb trauma, with pain intensity between 4 and 6 on a [0-10] numerical scale (NS). Patients were
injected at t0 with placebo (0.9% saline) or APAP (1g) and concomitantly, 125mg of APAP dissolved
in 1ml of hydroalcoholic solution (HAS), or placebo (HAS only) was applied in the left mucogingival
sulcus.
Results: NS evaluations were done at t10, t30, t120, t180 min after administration. Primary endpoint
was the pain intensity difference (PID) between t30min and t0. PID of both treatments were compared
by Student t test (p< 0.05 significance). Secondary endpoints were PID at other times. Results (mean
± SD) show no significant PID difference between bAPAP and ivAPAP respectively: t10min (-0.9 ± 1.3
vs -1.3 ± 1.8), t30min (-2.0 ± 1.8 vs -2.4 ±1.5), t120min (-2.9 ± 1.9 vs -3.3 ± 1.5), t180 (-2.1±2.2 vs 3.4±1.8).
Conclusions: bAPAP has a similar analgesic effect than ivAPAP in patients with pain of mild to
moderate intensity. This alternative to other routes would be useful in situations where oral/iv routes
are not available or in vulnerable patients for acute pain paroxysms.
459
NEW INSIGHT ON THE ANTI-NOCICEPTIVE EFFECTS OF ET1 A 4-AMINO-5-VINYL-3(2H)PYRIDAZINONE DERIVATIVE IN MICE
1
1
2
2
S. Pieretti , A. Di Giannuario , M.P. Giovannoni , C. Vergelli
1
Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome,
Department of Pharmacological Science, University of Florence, Florence, Italy
2
Background and aims: Owing to its long-lasting and to the complexity of involved mechanisms,
chronic pain often becomes resistant to treatment with traditional analgesics. For these reasons, the
identification of alternative therapeutic strategies based on new drugs effective in the treatment of
pain is one of the major focus in current pain research. Pyridazine derivatives show interesting
antinociceptive properties, and we recently synthesized a 4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1yl)ethyl]-5-vinylpyridazin-3(2H)-one derivative called ET1 that was 3-fold more potent than morphine
in reducing thermal nociception when centrally injected and 4-fold more potent when orally
administered. Binding studies demonstrated the ET1 selectivity for the adrenoceptors α 1A, α1B and α2A,
but not for the subtype α2C. (Biancalani et al., 2009 J Med Chem 52:7397-7409). Starting from these
evidences, in the present study we investigated the pharmacological effects induced by oral
administration of ET1 on the behavioural response to different chemical nociceptive stimuli.
Methods: In CD-1 mice, the following animal models were used: formalin test, capsaicin test, writhing
test and carrageenan-induced thermal hyperalgesia.
Results: In all above mentioned pain models, ET1 was able to increase nociceptive threshold starting
from the dose of 1 mg/kg.
Conclusions: The current study further indicates ET1 as a potent orally active long-lasting agent
effective against acute and inflammatory pain and suggests ET1 may be useful for clinical
applications.
460
NSAIDS MAY DELAY RECOVERY WHEN USED FOR MUSCLE PAIN
1
2
M. Rother , E.J. Seidel , I. Rother
1
1
2
IMR Partner GmbH, Graefelfing, Department Physical and Rehabilitation Medicine, Sophien- and
Hufeland-Clinic, Weimar, Germany
Background and aims: NSAIDs are frequently used to treatment exercise induced muscle pain. But
the results from previous studies are controversial. We investigated in two double-blind, placebocontrolled studies the kinetic profile of effects from exercise to full recovery for two NSAIDs.
Methods: The parallel-group study1 enrolled subjects with muscle pain ≥ 3 (out of 10) after walking
down stairs treated with placebo (n=48) or 200 mg ketoprofen (n=24) for 7 days. Cross-over study2 in
50 subjects with pain ≥ 5 (out of 10) after exercise of lower limbs were treated with placebo or 90 mg
etoricoxib.
Results: Ketoprofen caused a trend of pain reduction during the first 12 h of usage. But, higher pain
scores compared to placebo (p=0.0240) were shown for the total observation period. Most of the
negative effect was caused by a delay of recovery (p=0.0046). Etoricoxib caused long term antiinflammatory effects as shown by a reduction in CRP (p=0.0203). There is a trend for reduction of
pain at rest for the first 24 h. Peak torque and pain threshold at the tender point indicated a trend of
delayed recovery with etoricoxib.
Conclusions: NSAID use for muscle soreness may provide a modest analgesic effect in the early
phase. But consistent evidence for delayed recovery was found. The results imply that the
inflammatory reaction following muscle injury is essential for recovery. Also due to their general risk,
treatment of exercise induced muscle pain with NSAIDs cannot be recommended.
461
CENTRAL ANALGESIC EFFECTS OF DIPYRONE AND ITS METABOLITES IN A MODEL OF
INFLAMMATORY PAIN CAUSED BY ENDOTHELIN-1
1
1
2
S.D. Schroeder , A.P. Luiz , G.E.P. Souza , G.A. Rae
1
1
2
Universidade Federal de Santa Catarina, Florianópolis, Universidade de São Paulo, Ribeirão Preto,
Brazil
Background and aims: Endothelin-1 (ET-1) is a vasoconstrictor and nociceptive peptide that acts
through ETA and ETB GPCR receptors. Dipyrone is a pro-drug used clinically as analgesic and
antipyretic since 1922, but its mode of action is not yet completely understood. This study investigates
the analgesic effects of Dipyrone and two of its main metabolites in mice in a model of inflammatory
pain induced by ET-1 administration into the hind paw.
Methods: Male Swiss mice were treated with Dipyrone, 4-aminoantipyrine (4-AA) or 4-methylaminoantipyrine (4-MAA) via intraperitoneal (i.p.), intrathecal (i.t.) or local (subcutaneously into the
paw, s.c.) routes. Thirty, 15 or 20 minutes after the treatment, respectively, mice received a s.c.
injection of ET-1 (10 pmol) into the right hind paw and the time they spent licking the injected paw was
recorded (in seconds) over the next 30 minutes. They were then euthanized, and the difference in
weight of both hind paws assessed in order to determine the oedema caused by ET-1.
Results: All drugs effectively reduced ET-1-induced licking time when given via i.p. (Dipyrone: 50-100
mg/kg; 4-AA: 50 mg/kg; 4-MAA: 50-100 mg/kg) or i.t. (Dipyrone: 25-100 mcg/site; 4-AA: 5-100
mcg/site; 4-MAA: 200 mcg/site) routes, but not when injected into the hind paw (up to 600 mcg/site).
None of the drug treatments modified ET-1-induced paw oedema, except the highest dose of i.t. 4AA.
Conclusions: The results suggest that the analgesic effects of Dipyrone and its metabolites against
ET-1-induced inflammatory pain are promoted mainly via central actions.
462
AK106-001616, A CPLA2 INHIBITOR, SHOWS INHIBITORY EFFECTS ON INFLAMMATORY AND
NEUROPATHIC PAIN
H. Shimizu, J. Nakamura, A. Ito, M. Takeda, Y. Endo, K. Saito, T. Kozaki, M. Shoda, H. Kuriyama
Asahi Kasei Pharma Corporation, Izunokuni-shi, Japan
Background and aims: Cytosolic phospholipase A2 (cPLA2) preferentially cleaves arachidonic acid
from membrane phospholipid, resulting in the various inflammatory mediators such as prostaglandins
and leukotrienes. We created a novel and potent cPLA2 inhibitor AK106-001616 (AK106), and
investigated the inhibitory effects on pain.
Methods: Inflammatory pain was evaluated with rat carrageenan model established by carrageenan
injection into the hind paw. Drugs were administered orally 1h before carrageenan injection, and 5hr
after, Randall Selitto assay was performed. Neuropathic pain was evaluated with rat chronic
constriction injury model. Four loose ligatures were placed on the sciatic nerve with 4-0 suture silk
thread under isoflurane anesthesia on day 0, and drugs were administered orally for 7 days from day
8. Randall Selitto assay was performed 2 hours after the last dose (day 14).
Results: The analgesic effect on inflammatory pain of AK106 was dose-dependent, and maximal at
dose of 30 mg/kg, which was comparable with naproxen (30 mg/kg). The analgesic effect on
neuropathic pain of AK106 (30 mg/kg) was equal to pregabalin (30 mg/kg), but, naproxen (10 mg/kg)
and celecoxib (30 mg/kg) did not show analgesic effects.
Conclusions: AK106 may provide superior treatment for pain in a wider spectrum of pain condition.
463
COMPARATIVE EFFICACY AND SAFETY OF NIMESULIDE: SYSTEMATIC ANALYSIS OF
RUSSIAN CLINICAL STUDIES
1
A.E. Karateev , G. Shvartsman
2
1
Federal State Budget Institution “Scientific Research Institution of Rheumatology” of the Russian
2
Academy of Sciences, Moscow, Dept of Neurology, North-West State Medical University Named
After Mechnikov, Saint-Petersburg, Russia
Nimesulide is an efficient analgesic used worldwide for short-term relief of moderate and severe pain.
In Russia it is used since 1995 and is one of the most popular NSAIDs.
Material: Search in English and Russian for nimesulide studies conducted on Russian population.
Results: Twenty one Russian clinical studies were found from 1995-2008; efficacy and safety of
nimesulide 200-400 mg/day (1590 patients) was evaluated. All studies have relatively low methodic
level - open and mainly short-term, up to 4 weeks. Active control found were mainly NSAIDs, e.g.
diclofenac, paracetamol and tramadol (526 patients). Nimesulide was mainly tested at rheumatic
diseases (Rheumatoid Arthritis, Osteoarthritis, low back pain), acute traumas, in stomatology and
urology. In all studies, analgesic and inflammatory effect of nimesulide was equal or exceeded the
reference drugs; significant improvement (>50% vs. baseline) occurred in 40-90% of patients.
Nimesulide tolerability is relatively good. Compared to other NSAIDs, it caused lesser ulceration and
multiple GIT erosions (1.6% vs. 10.6%, р=0.001), less arterial hypertension (1.6% vs. 5.5%, р=0.001),
and less increase in transaminase level (0.9% vs. 2.5%, р< 0.05). However, dyspepsia frequency was
similar: 9.1% & 10.8% (р=0.102). In nimesulide group, some complications not reported in control
groups were noticed: edema (3 cases), urticaria (3 cases), blurred vision (1 case), and slight intestinal
bleeding (1 case). Treatment withdrawals due to adverse effects were less than in control group: 1.4%
vs. 2.3% (р< 0.05). No serious hepatotoxic complications were registered.
Conclusion: According to Russian clinical studies, nimesulide is efficient and relatively safer.
464
THE EFFECTS OF PRENATAL MORPHINE EXPOSURE ON PAIN RESPONSE
M. Amini, A. Alijarahi
Qazvin Azad University, Qazvin, Iran
Background: Drug abuse during pregnancy is a growing problem in all developed countries of the
world. Maternal drug abuse affects the developing system and its long-term effects can persist till
adulthood so it can decreases the rate of their maturation. Since endogenous opioid induced
analgesia, and morphine can interact with it, Thus the present study was designed to determine
whether the exposure to the morphine during gestation permanently alter pain response.
Objective: To determine the effects of prenatal morphine exposure on pain response.
Materials and methods: 12 Pregnant rats were divided to morphine and control groups. Morphine
was administrated (S.C) to female rats twice a day (08h and 20h) on gestational days 11-18, ( 5
mg/kg morphine for 3 days and 10mg/kg for 5 days). Analgesic response of pups (P90, n=6) were
tested by formaline test.
Finding: The results of our experiment demonstrated that prenatal morphine exposure rats exhibited
significantly lower pain thersholds.
Conclusion: Prenatal morphine exposure impair pain sensitivity.
465
DRUG INFORMATION IN PALLIATIVE CARE: IDENTIFYING AUTHORIZED AND OFF-LABEL
USES OF OPIOID ANTAGONISTS FOR INCLUSION IN THE PALLIATIVE CARE FORMULARY
1
1
V. Barnett , D. Kendall , A. Wilcock
1
2
2
University of Nottingham, Palliative Medicine, Nottingham University Hosptials, Nottingham, UK
Background and aims: Palliative care patients have specific needs and a limited prognosis. These
circumstances result in off-label prescribing of drugs. Within palliative care the opioid antagonists,
naloxone and naltrexone, have several off-label indications. Approved indications include opioidoverdose reversal, ex-opioid addiction and opioid-induced constipation. Off-licensed indications
include chronic pruritis, ex-alcohol addiction, opioid-induced hyperalgesia, cancer and auto-immune
diseases and pain.
This Palliative Care Formulary (PCF) is a core textbook laying out guidelines for managing patients in
palliative care. Guidelines usually focus on licensed uses of drugs, consequently the PCF is essential
for off-label prescribing. The principal aim was to produce updated versions of the opioid antagonists,
th
naloxone, naltrexone and oxycodone monographs in the PCF 5 edition.
Methods: A PubMed and Embase literature search was conducted from January 2011 to October
2012, according to the Standard Operating Procedures published by the editors of the PCF. The
results were used to update the monographs for the PCF5.
Results: 1839 papers relating to opioid-antagonists in palliative care were retrieved. 34 texts
remained following abstract review, and 28 changes were made to the monographs. Three major
areas of change were the development of opioid-combination products, naltrexone in cancer and
auto-immune diseases, and naloxone associated with pulmonary oedema. An area of interest was
using ultra-low dose naloxone for opioid-induced hyperalgesia.
Conclusions: The study highlighted the significant progress in this field within a two-year period.
Continued updating of the PCF is a necessary task, ensuring its clinical relevance for specialists,
ultimately benefitting patients receiving their care.
466
OPOID INDUCED HYPOGONADISM AND WHAT TO DO ABOUT IT IN MALES?
S.S. Bhayani, A.J. Ravenscroft
Pain Management Unit, Nottingham City Hospital, Nottingham, UK
Background and aims: Approximately 12% patients with persistent non cancer pain use strong
opioid analgesics in the UK. Long term opiate administration affects the hypothalamic-pituitaryadrenal axis, inhibit the gonadotrophin luteinising hormone (LH) which is involved in testosterone
production and also directly inhibit testosterone production.This can consequently induce
hypogonadism.
Circulating oestrogens and androgens are mostly found bound to Sex Hormone Binding Globulin
(SHBG).When SHBG levels are elevated there is likely to be less free testosterone available.It has
been found that there are no clear guidelines regarding the treatment of low testosterone levels in
males on long term opiates.
Methods: We audited 15 males on long term opiates and measured their testosterone, LH and SHBG
levels. Measuring testosterone would give the total testosterone level, low LH would indicate
hypopituitarism. The data collected was the patient's age, pain condition, opiate drug, hormone levels,
patient referral to an endocrinologist and treatment with sustanon. Patients were questioned on
symptoms of low testosterone.
Results: It was found 11 out of the 16 patients had a low testosterone level. Four patients were
treated for their low testosterone levels, three patients were commenced on sustanon injections. One
patient was treated with testogel.
Recommendation:
[Algorithm for the guidance of management of males ]
Conclusion: Opoid-induced hypogonadism seems to be a common complication of its use in chronic
pain. Patients on opoid therapy should be prospectively monitored. Our algorithm for guidance is the
simple and easy way to manage patients on long term opoid treatment.
467
MORPHINE STIMULATES ANGIOGENESIS AND TUMOR CELL PROLIFERATION
S. Bimonte, A. Barbieri, G. Palma, C. Arra, A. Cuomo
Istituto Nazionale dei Tumori Fondazione G.Pascale, Naples, Italy
Background: Morphine, is considered “the gold standard” used to relieve pain and suffering. In
addition, it has been showed that morphine is important in regulation of neoplastic tissue.
Accumulating evidence suggests that morphine can affect proliferation and migration of tumor cells as
well as angiogenesis. Angiogenesis, is critical for tumor progression from quiescent to malignant. The
effect of morphine on tumor growth is still contradictory, as both growth-promoting and growth
inhibiting effects have been observed.
Methods and principal findings: In order to understand the role of morphine in cancer cell growth
and angiogenesis, we performed in vitro studies by using MDA.MB231 cancer cell lines and Huvec
cells. Treatment of cell lines with different concentration of morphine showed that morphine stimulates
cell proliferation and angiogenesis. In addition, morphine inhibits apoptosis and promotes cell cycle
progression of breast cancer cell lines.
Conclusion and significance: The present data demonstrate that that morphine stimulates
angiogenesis and promotes tumor growth and proliferation.
468
LEUKOCYTIC OPIOID RECEPTORS AND NEUROIMMUNE INTERACTIONS IN THE CONTROL
OF NEUROPATHIC PAIN
M.O. Celik, D. Labuz, H. Machelska
Department of Anesthesiology, Charité-University Berlin, Campus Benjamin Franklin, Berlin, Germany
Background and aims: We have recently shown that immune cells containing opioid peptides
attenuate neuropathic pain. Although leukocytes also express opioid receptors, their significance to
pain transmission has not been addressed so far. Here we tested the hypothesis that upon activation
of opioid receptors on leukocytes, these cells release opioid peptides which activate neuronal
receptors to ameliorate neuropathic pain.
Methods: As a model of neuropathy we used a chronic constriction injury of the sciatic nerve in mice.
Mechanical sensitivity was evaluated with von Frey filaments. Immune cells infiltrating damaged
nerves were isolated 2 days following the injury, and the secretion of opioid peptide Met-enkephalin
was examined using radioimmunoassay.
Results: Selective agonists of µ-, δ- and κ-opioid receptors injected at the nerve injury site
substantially elevated mechanical thresholds in vivo. These analgesic effects were attenuated
following depletion of leukocytes in injured nerves. In vitro, the opioid receptor agonists dosedependently secreted Met-enkephalin from leukocytes. This release was abolished by the respective
opioid receptor antagonists, by blocking Gαi or Gβγ, but not Gαs subunits, and by removing
2+
intracellular, but not extracellular Ca . Additionally, Met-enkephalin release was attenuated by
inhibitors of phospholipase C or inositol 1,4,5-trisphosphate receptors.
Conclusions: Our results indicate that activation of opioid receptors on immune cells leads to the
2+
Ca -regulated secretion of Met-enkephalin and decreases neuropathy-induced mechanical
sensitivity. Thus, targeting both peripheral neuronal and leukocytic opioid receptors migth be an
attractive approach for efficient and side effects-free control of painful inflammatory neuropathies.
469
PHARMACOKINETIC MODELING FOR OPTIMIZATION OF OPIOID DOSING REGIMENS
1
1
2
3
D. Daly , O. Linares , D. Stefanovski , R. Boston , Plymouth Pharmacokinetic Modeling Study Group
1
2
Plymouth Pharmacokinetic Modeling Study Group, Plymouth, MI, Biomedical Sciences, Cedars3
Sinai Medical Center, Hollywood, CA, Biostatistics, University of Pennsylvania, Kennett Square, PA,
USA
Background and aims: An 87 kg man with severe pain caused by prostate cancer metastasized to
the lumbar spine is hospitalized to receive IV morphine. The standard weight-based morphine dosing
guideline provides for a dose of 0.1 mg/kg IV every 4 hours. Morphine´s therapeutic range lies
between the minimum effective concentration (MEC) of 20 mg/L and its maximum therapeutic
concentration (MTC) of 80 mg/L. Morphine's plasma clearance rate is 1.43±0.69 L/h/kg.
Aim: To show the use of pharmacokinetic (PK) modeling to determine the dosage regimen to keep
the patient's plasma opioid concentration within the “therapeutic range” bounded by MEC and MTC
during the entire dosing interval.
Methods: We used PK modeling to predict plasma morphine concentration time courses for IV
morphine boluses repeated every 4 hours using 10 mg, 15 mg, and 20 mg doses.
Results: PK modeling shows that only the 20 mg dose keeps the patient within the therapeutic range
for the entire dosing interval. The 10 mg dose falls below the MEC after 1.5 hours. The 15 mg dose
falls below the MEC after 2 hours. During those times the patient experiences excruciating pain.
Conclusions: PK modeling assists clinicians to design a point-of-care opioid dosing regimen to
manage acute and chronic pain to keep the patient's plasma opioid concentration within the
therapeutic range for the entire dosing interval.
470
RISK OF PHARMACODYNAMIC INTERACTIONS IN PATIENTS RECEIVING ORAL
ANTICOAGULATION THERAPY DURING TREATMENT IN A PAIN CLINIC
A. Lindekær, I.T. Jørgensen, A. Weihe, T.P. Enggaard
Pain Clinic, Department of Anaesthesiology, Glostrup Hospital, Copenhagen University Hospital,
Glostrup, Denmark
Background and aim: The drugs of choice for the prevention of thromboembolism are the Vitamin K
Antagonists (VKAs). Warfarin and phenprocoumon are the only available VKAs for oral
anticoagulation therapy in Denmark, and the use is rising rapidly. Pharmacodynamic interactions
between VKAs and other drugs occur frequently and may cause excessive anticoagulation. The
combined treatment of VKAs and analgesics such as tramadol, acetaminophen (paracetamol) and
nonsteroid antiinflammatory drugs (NSAIDs) are known to induce bleeding disorders. The aim of the
study was to monitor the number of patients in anticoagulation treatment referred to a pain clinic and
identify potential hazardous interactions between VKAs and analgesics.
Methods: The study was designed as a retrospective pilot study. All patients referred to the pain clinic
in the period February 1 - April 30, 2013 were included.
Results: A total number of seventy-five referrals were registered and five patients in long-term
warfarin therapy were identified. All five patients were co-treated with acetaminophen and tramadol.
No patients were treated with NSAIDs.
Discussion: Inducing variations in a stable anticoagulation therapy may be associated with an
adverse outcome. In our study we found five cases with potential warfarin-tramadol and warfarinacetaminophen interactions. Tramadol and acetaminophen are some of the most used analgesics.
Start or discontinuation of pain treatment may cause interactions and increase the risk of adverse
events.
Conclusion: Our data indicates that patients in oral anticoagulation therapy referred to pain clinics
are frequently treated with analgesics known to cause interactions. Special attention is required to
avoid bleeding disorders.
471
TAPENTADOL IN CHRONIC PAIN: A PRELIMINARY STUDY
1
2
M.T. Flor de Lima , N. Coutinho , M.M. Melo
1
2
2
Multidisciplinary Pain Unit, Pharmacy, Hospital Divino Espírito Santo, Ponta Delgada, Portugal
Background and aims: Tapentadol is a new type of opioid. It was introduced in our hospital in July
2012 in collaboration with the Pharmacy Department who makes the management and registration of
opioids in hospitalized patients and in patients from the Pain Unit and Oncology Day Care. Elderly
patients attended are 49% (62% have musculoskeletal pain-Poster Efic 2011). The aim of this study
was to evaluate the patients treated with Tapentadol.
Methods: Patients treated with Tapentadol were selected and medical records were revised
(demographic data, baseline diseases, type of pain, previous medication, reason for Tapentadol
selection, side effects, evolution of pain). The effects on pain were evaluated by numerical rating
scale and functional status by SF 36 Questionnaire.
Results: In the initial evaluation we analyzed 162 patients: 119 female, 43 male; mean age 60.5
years; 48.8% lumbar/cervical pain; 39.5% knee or hip pain; 27.2% neuropathic pain. In the second
evaluation, patients who stopped medication (25.9 %) and those in titration before a four week period
were excluded. The remaining 107 patients had nausea or vomiting (10.3%), somnolence (8.4 %);
constipation (6.5%). Tapentadol was stopped due to nausea or vomiting (19%), drowsiness (19%)
and 7.1% didn't tolerate other opioids.
Conclusions: The Tapentadol is well tolerated, with few side effects and effective in reducing pain
and in functional status. It's a good option to rachis and joint pathology and elderly can use it safely. A
follow-up more than one year is needed for the evaluation of subgroup diseases.
472
CHRONIC PAIN MANAGEMENT WITH TAPENTADOL - 9 MONTHS EXPERIENCE
J.M.F.S. Freitas, R. Vieira
Internal Medicine, SESARAM, Funchal, Portugal
Background and aims: The physicians were faced with patients in chronic pain, and had several
important tasks. The first was to assess the pain and its various causes, including physical and
psychological components. As pain itself is a bio-psycho-social phenomenon, all of these aspects had
to be addressed in the history and evaluation of the patient. Only when a proper evaluation was made
could the appropriate treatment be carried out
Methods: Patients (n = 25) Ages Eligible: 20 Years and older; Genders Eligible: Both with at least a 3month history of opioid and/or non-opioid analgesic use for chronic pain, dissatisfaction with current
treatment, and an average pain intensity score of at least 5 on an 10-point numerical rating scale
(NRS; 0 = ´no pain,´ 10 = ´worse pain ever´) were titrated to an optimal dose of tapentadol ER (50150 mg bid) during 3-weeks.
Results: The primary outcome was the change in average pain intensity and improvement in daily life
activities. A total of 92% (23/25) patients reported an improvement in pain intensity from the start to
the end of the titration phase; Adverse events were monitored throughout the study. The most
common adverse events included nausea, anxiety, diarrhea and oral and genital ulcers. Limitations of
this study are related to small sample used.
Conclusions: Compared with other treatments, tapentadol ER 50-150 mg bid provided a significant
improvement in daily life activities, mood, together with a down grade in experienced pain. However
and due to the small sample these results still aren't statistically significant.
473
LIFE CHANGING MOLECULE - 2 CASE REPORTS
J. Freitas, R. Vieira
Internal Medicine, SESARAM, Funchal, Portugal
First case report: Female patient, 83-year old, past history of diabetes, arterial hypertension with
bilateral hip and left knee prosthesis. Complaints started without trauma characterized by intense pain
in right hip joint, associated with great limitation in walking. The radiograph of the pelvis demonstrated
detachment of the prosthetic right hip joint in relation to the acetabulum. She began treatment for pain
st
(intense with a Grade of 8 in a scale from 0-10). 1 week: meloxicam 15 mg/day; paracetamol 1000
mg tid; metamizol SOS. The pain reduced to a grade of 6-7, being yet described as very intense and
nd
life limiting. 2 week: tapentadol 50 mg bid was added with immediate response. There was the need
to increase firstly to 100 mg bid and afterwards to 150 mg bid. The adjustment of tapentadol left aside
rescue therapy and the patient got back to daily life activities.
Second case report: Male patient, 48 year old, thoracolumbar excruciating pain, Grade of 9 in a
scale from 0-10, associated with paresthesias in the lower limbs. The pain was localized in the
paravertebral middle third of the dorsal region and worsened with hyperextension. Past medical
history revealed pneumonia. The nuclear MRI showed mild discal protrusion of L5-S1, thoracic
kyphosis, anterior thoracic disc herniation at D7-D8 in mediolateral position without cord compression.
The patient started on tapentadol 50 mg bid, associated with paracetamol 1000 mg tid and a short
period of diclofenac 75 mg bid. This patient lives clinically asymptomatic with tapentadol to 100 mg
bid.
474
CONDITIONAL KNOCKOUT OF MU OPIOID RECEPTORS IN PRIMARY AFFERENT NAV1.8
NEURONS REVEAL THEIR CONTRIBUTION IN ANALGESIA UNDER INFLAMMATORY PAIN
1
1
2
1
R. Weibel , D. Reiss , J.N. Wood , B.L. Kieffer , C. Gaveriaux-Ruff
1
1
Translational Medicine and Neuorgenetics, IGBMC Institut de Génétique et de Biologie Moléculaire
et Cellulaire, Translational Medicine and Neurogenetic Programme, UdS Université de Strasbourg,
2
INSERM U 964, CNRS UMR 7104, Illkirch, France, Molcular Nociception Group, Wolfson Institute for
Biomedical Research, University College London, London, UK
Background and aims: Opiates are powerful analgesics to treat severe pain, and act via mu opioid
receptors. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or
respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu
opioid receptors as targets for pain treatment.
Methods: We generated conditional knockout (cKO) mice where mu opioid receptors are deleted
specifically in primary afferent Nav1.8-positive neurons. Mutant animals were studied for nociception,
inflammatory pain, opiate-induced analgesia and constipation.
Results: cKO mice showed a 76 % decrease in mu receptor-positive neurons and a 60% reduction of
receptor mRNA in dorsal root ganglia. Mutant mice showed unchanged responses to nociceptive
stimuli, morphine antinociception and tolerance to antinociception in acute pain models. In the paw
Complete Freund's Adjuvant inflammation model, opiate-induced (morphine, fentanyl and loperamide)
analgesia was reduced in mutant mice as compared to controls, and abolished at low doses whereas
morphine-induced constipation remained intact.
Conclusion: We therefore genetically demonstrate that mu opioid receptors partly mediate opiate
analgesia at the level of Nav1.8 sensory neurons. Here, this mechanism operates under conditions of
inflammatory pain, but not nociception. Pharmacology suggests that peripheral opiates may be
clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors
represent targets to alleviate some forms of persistent pain.
Acknowledgements: This work was supported by Université de Strasbourg, CNRS, INSERM, the
french Agence Nationale de la Recherche ANR LYMPHOPIOID, NIH-NIAAA #16658, NIH-NIDA
#05010 and EU GENADDICT/FP6 005166 grants.
475
MORPHINE INDUCED ANALGESIA IN A DOUBLE-BLIND, RANDOMIZED HUMAN
EXPERIMENTAL PAIN STUDY: PRIMARILY EFFECTS ON TONIC PAIN
1
1
1
I. Larsen , A. Estrup Olesen , C. Brock , A. Mohr Drewes
1,2
1
Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg,
2
Denmark, Center for Sensory-Motor Interaction, Department of Health and Science and Technology,
Aalborg University, Aalborg, Denmark
Background: Most investigations on opioid effects have used models of phasic pain. Such brief
stimuli may be limited in their ability to faithfully simulate natural and clinical painful experiences.
Therefore, the aim was to investigate differences in sensitivity of various pain models in distinguishing
morphine analgesia.
Method: The study was a double-blind, two-way crossover study. Forty healthy participants were
included. Each participant received morphine 30 mg (2 mg/mL) as oral solution or placebo in
randomized order. To cover both deep and superficial pain and tonic vs. phasic stimulations a
comprehensive multi-modal, multi-tissue pain testing program was performed.
Results: Morphine showed analgesic effect in tonic experimental pain models: Muscle pressure
(F=5.30, P=0.03); bone pressure (F=3.98, P=0.05); rectal pressure (F=4.39, P=0.04) and the cold
pressor test (F=25.3, P< 0.001). In contrast morphine showed no analgesic effect on the more phasic
experimental pain models: Skin heat (F=0.21, P=0.65); rectal electrical stimulation (F=0.03, P=0.86)
or rectal heat stimulation (P=0.94).
Conclusion: This study demonstrated discriminative effect of morphine, as analgesia was verified in
tonic pain but not in phasic pain models. Therefore, tonic pain models, which likely mimic clinical pain
to a higher degree, should be included when opioids effects are investigated in human experimental
studies.
476
MORPHINE INDUCED CHANGES IN THE CINGULATE-OPERCULUM BRAIN NETWORK
UNDERLYING RECTAL PAIN
1
1
2
3
D. Lelic , A.E. Olesen , H. Gregersen , A. Dahan , A.M. Drewes
1
1,4
2
Mech-Sense, Aalborg Hospital, Aalborg University Hospital, Aalborg, Denmark, College of
3
Bioengineering, Chongqing University, China and the GIOME Institute, Beijing, China, Department of
4
Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands, Department of Health
Science and Technology, Center for Sensory-Motor Interactions (SMI), Aalborg University, Aalborg,
Denmark
Background and aims: The effect of opioids on brain networks underlying rectal evoked potentials
(EPs) has not been investigated before. By utilizing brain source connectivity, we aimed to explore
whether changes in the brain networks underlying painful rectal EPs would reflect changes in pain
scores due to morphine.
Methods: Twenty healthy volunteers were included in this placebo-controlled cross-over study.
Sensory and pain thresholds to electrically induced rectal stimulation were taken before (baseline)
and 60 minutes after placebo/morphine (30mg) administration. The stimulation intensity required to
evoke moderate pain at baseline was applied for EPs. The pain score of this stimulation intensity was
recorded again 60 minutes after placebo/morphine administration. 62-channel EPs were recorded for
both arms. Amplitudes and latencies were analysed and brain source connectivity analysis was done.
Differences in EP parameters were correlated to changes in subjective pain ratings.
Results: Morphine attenuated sensory and pain thresholds (P≤0.02). The stimulation intensity
required to evoke moderate pain was attenuated in both placebo and morphine arms (P< 0.05).
Amplitudes were attenuated due to placebo (P< 0.05), whereas they remained stable due to
morphine. A dominating cingulate-operculum network to rectal pain was seen. Cingulate source
shifted anteriorly in the morphine arm (P< 0.001) and this shift was positively correlated to the change
in the pain score (P< 0.05).
Conclusions: Pain relief due to morphine is associated with neuroplastic changes within cingulate
cortex and therefore these results provide measures which could be used as biomarkers of opioid
effects on painful diseases in visceral structures.
477
ADDING KETAMINE FOR THE TREATMENT OF MORPHINE TOLERANCE: A
PHARMACOKINETIC PERSPECTIVE IN THE RAT
1
1
2
2
1
T.O. Lilius , V. Jokinen , M.S. Neuvonen , M.O. Niemi , P.V. Rauhala , E.A. Kalso
1
1,3
2
Pharmacology, Institute of Biomedicine, University of Helsinki, Department of Clinical
3
Pharmacology, Pain Clinic, Department of Anesthesiology and Intensive Care, Helsinki University
Central Hospital, Helsinki, Finland
Background and aims: The positive effects of ketamine in augmenting morphine analgesia and
inhibiting the development of morphine tolerance have been suggested to be mediated via a
pharmacodynamic interaction. We studied the effects of acute ketamine in opioid-tolerant rats from
the pharmacokinetic perspective.
Methods: Morphine tolerance was produced using Alzet pumps delivering morphine 6 mg/day. On
day 5, rats received subcutaneous racemic ketamine (10 mg/kg) with no extra acute morphine doses.
The tail-flick test was used. Tissue concentrations were quantified using high pressure liquid
chromatography-tandem mass spectrometry.
Results: In the morphine-naïve rat, 10 mg/kg of ketamine caused no antinociception compared with
saline, whereas in the morphine-tolerant rat major antinociception was observed (57% MPE at 90
minutes) lasting up to 150 minutes after ketamine. In the whole brain of morphine-tolerant ketaminetreated rats, the mean morphine, ketamine and norketamine concentrations were increased 2.1-, 1.4and 3.4-fold compared to the rats that had been treated with morphine or ketamine only. In the liver of
morphine-tolerant ketamine-treated rats, the mean ketamine concentration was sixfold compared to
the morphine-naïve rats suggesting an inhibition of ketamine elimination by morphine. When the
same dose of ketamine was administered to tolerant rats whose morphine pumps had been removed
two days earlier, no similar effect was seen suggesting an morphine-dependent inhibition of ketamine
elimination.
Conclusion: The positive effects of ketamine in attenuating morphine tolerance are mediated also via
a pharmacokinetic interaction between the two drugs as the concentrations of both ketamine and
morphine are increased in the brain.
478
DOES THE HUMAN Μ-OPIOID SYSTEM MODULATE PREFERENCE FOR CT OPTIMAL TOUCH?
1
1
1
1
2
G.E. Løseth , O. Chelnokova , J. Riegels , M.H. Eikemo , F. Willoch , S.G. Leknes
1
1
2
Department of Psychology, Faculty of Medicine, University of Oslo, Oslo, Norway
Background and aims: CT afferents are activated by caress-like pleasant touch - a social reward
associated with increased β-endorphin release in non-human primates, and shown to reduce
experimental pain. Studies in non-human animals suggest that the opioid system specifically
mediates preference for the most valuable rewards. We hypothesized that preference for CT optimal
touch would increase with opioid agonism and decrease with opioid antagonism in humans.
Methods: In a randomized double blind cross-over study 30 healthy males orally received a µ-opioid
agonist (morphine 10 mg), a non-selective opioid antagonist (naltrexone 50 mg) or placebo. Soft
brush strokes were administered to their forearms with three different speeds: 0.3 cm/s, 3 cm/s (CT
optimal) and 30 cm/s. In a hedonic task, pleasantness ratings and pupil diameter change was
recorded for each 15-second trial. In a preference task, participants manipulated individual trial
durations through key presses while total task duration was fixed. Pupil responses and stimulus
durations (log transformed) were analyzed using a 3x3 multiple regression design with drug type and
brushing velocity as main factors. Session- and stimulus numbers were included as nuisance
regressors.
Results: As expected, 3 cm/s was the preferred stimulus. Compared to placebo (P), morphine (M)
increased and naltrexone (N) decreased preference for this CT optimal velocity only, as measured by
duration (median M=19s, P=18s, N=17s, M>P p=.091, P>N p=.001) and pupil response
(M>P p=< .001, P>N p=< .001).
Conclusions: Overall, our results point to a role of the endogenous opioid system for CT optimal
touch in humans.
479
SLOWED EEG RHYTHMICITY IN PHARMACO-EEG SPECTRAL INDICES AFTER LOW DOSE
REMIFENTANIL IS CORRELATED TO THE ANALGESIC EFFECT IN HEALTHY VOLUNTEERS
1
1,2
L.P. Malver , C. Graversen , A.M. Drewes
1
1,3
2
Mech-Sense, Department of Gastroenterology, Mech-Sense, Department of Radiology, Aalborg
3
University Hospital, Center for Sensory-Motor Interactions (SMI), Department of Health Science and
Technology, Aalborg University, Aalborg, Denmark
Background and aims: To pursue personalized medicine, novel approaches for assessment of
individual effect of opioids are warranted. This may be achieved by multivariate pattern analysis
(MVPA) of the alterations in the electroencephalography (EEG) after drug administration to determine
the overall alterations in several spectral indices simultaneously.
Methods: To verify this approach, we recorded 62 channel resting electroencephalography (EEG) in
21 healthy males before and during remifentanil infusion in a placebo-controlled double-blind crossover study. EEG spectral indices were extracted by a continuous wavelet transform and normalized
into spectral distribution in the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz) and beta (12-32 Hz)
bands. Alterations relative to pre-treatment responses for all subjects were calculated for both
remifentanil and placebo and used as input to the MVPA, which was implemented as a support vector
machine (SVM) applied in regression mode. Additionally, subjective pain scores immediately before
the EEG recordings were obtained for bone and heat pain.
Results: Compared to placebo, remifentanil increased the delta band and decreased the theta and
alpha band oscillations as a mean over all electrodes (all P< 0.001). The MVPA had a classification
performance of 88.1% (P< 0.001) in the F3 and F5 channels. By calculating the overall alteration of
the spectral indices as the mean regression value of the SVM for these channels, the pharmaco-EEG
findings were correlated to individual changes in heat pain (P=0.03).
Conclusion: This study has shown that MVPA of pharmaco-EEG is a novel approach for monitoring
the individual efficacy of opioids.
480
THE EFFECTS OF PENTAZOCINE ON BISPECTRAL INDEX VALUES DURING NITROUS OXIDE
ISOFLURANE ANESTHESIA
1
1
1
1
2
Y. Yamanishi , H. Nagasaka , T. Nakamura , Y. Horikoshi , K. Onuki , N. Matsumoto
1
1
2
Dept. of Anesthesiology, Saitama Medical University, Moroyama-Machi, Dept. of Anesthesiology,
Meikai University, Sakado, Japan
Background: Pentazocine is often used as an analgesic perioperatively. It is reported that
pentazocine increases bispectral index (BIS) values during nitrous oxide (N 2O) sevoflurane
anesthesia. However, another anesthetics, such as isoflurane might affect pentazocine-induced BIS
changes. Therefore, we have examined the effects of pentazocine on BIS values during N 2O
isoflurane anesthesia.
Methods: The study was approved by the ethics committee of our institution. ASA I patients,
scheduled for elective oral surgery were enrolled in the trials. Patients were randomly assigned to one
of 2 groups: pentazocine 0.6mg/kg group (n = 15) or saline (n = 15). Anesthesia was induced with
thiopental and vecuronium bromide and maintained with N2O (64-67%) -isoflurane (0.7%). Patients
were assigned to receive either a bolus of pentazocine or saline 15 min after the intubation. Fifteen
min after the intubation, mean arterial blood pressure (MAP), heart rate (HR), and BIS values was
recorded as a baseline values. MAP, HR, and BIS values were measured every 5 min after the
intubation up to 30 min.
Results: MAP and HR showed no significant differences among the 2 groups during the study. BIS
values were significantly increased at from 5 to 15 min from the baseline values in pentazocine group
(P< 0.01). BIS values in the both groups were not significantly differences.
Conclusions: We have found that the BIS value is increased by pentazocine even during isoflurane
anesthesia. The depth of sedation during general anesthesia should be assessed carefully by using a
BIS monitor when pentazocine is also administered.
481
THE EFFECTS OF SEVOFLURANE CONCENTRATIONS ON BLOOD PRESSURE, HEART RATE,
AND BISPECTRAL INDEX AFTER INTRAVENOUS ADMINISTRATION OF PENTAZOCINE
1
1
2
2
1
1
1
T. Nakamura , Y. Horikoshi , Y. Yamanishi , K. Onuki , H. Nakayama , H. Nagasaka , N. Matsumoto
1
2
Anesthesiology, Saitama Medical University, Moroyama-machi, Anesthesiology, Meikai University,
Sakado, Japan
Backgrounds: It is reported that pentazocine increases bispectral index (BIS) values during 1%
sevoflurane anesthesia. Although sevoflurane has concentration-dependently suppressive actions on
the central nervous systems, it has been reported as sevoflurane concentration is increased, the
incidence of abnormal excitatory action is higher in EEG activity in the frontal lobe. However, there are
no reports on the concentration-dependent effects of sevoflurane regarding the pentazocine-induced
BIS changes.
Methods: Patients, ASA I, were randomly assigned to one of 2 groups: 1% sevoflurane group (n=41)
or 2% sevoflurane group (n=24). Anesthesia was induced with thiopental and vecuronium bromide
and maintained with N2O (64-67%) -sevoflurane. Fifteen min after the intubation, pentazocine
(0.6mg/kg) was administered intravenously (IV). At this time, mean arterial blood pressure (MAP),
heart rate (HR), and BIS values was recorded as a baseline values.
Results: In 1% sevoflurane group, BIS values were significantly increased from 5 to 15 min after IV
pentazocine. In 2% sevoflurane group, BIS values were significantly increased 15 min after IV
pentazocine. However, BIS values in 1% sevoflurane group were significantly larger from baseline to
15 min after IV pentazocine than those in 2% sevoflurane group. MAP and HR showed no significant
differences between the 2 groups during the study.
Conclusions: It is confirmed that BIS values were significantly increased after IV pentazocine during
1% sevoflurane anesthesia in our present study. As a first report, present results showed that BIS
values were significantly increased at 15 min from the baseline values after IV pentazocine during 2%
sevoflurane anesthesia.
482
EFFICACY OF FENTANYL PECTIN NASAL SPRAY IN ELDERLY PATIENTS WITH NON-CANCER
BREAKTHROUGH PAIN
R. Salazar Vecino
Hospital Comarcal d´Inca, Inca, Spain
Introduction: Breakthrough pain in non-cancer patients has the same characteristics as pain in
neoplasic cases. The incidental pain in relation to motor activity is the most frequent and predictable
form of presentation.
Material and methods: A 6-week evaluation was made of 20 patients, (18 females, 2 males; mean
age 74.7 years) with vertebral pathology and gonarthrosis. Resting pain was controlled with
oxycodone/naloxone, tapentadol, fentanyl TTS and hydromorphone, in addition to other drugs. Base
treatment was not modified during the study to evaluate the efficacy of fentanyl pectin nasal spray.
To this effect, the following was measured:
· VAS: Pain Visual Analog Scale at rest and in movement, after 0, 2, 4 and 6 weeks;
· SF-12 and EQ-5D scales (Quality of Life)
· Oswestry functional test (Disability); and
· MOS (Sleep Problems Index)
Were measured after 0, 4 and 6 weeks.
· Patient Global Impression of Change (PGIC) was also lastly rated.
Results: Improved all measured parameters:
Resting VAS: 1,7 - 1,5 - 1,3 and 1,2
Moving VAS: 6,55 - 3,35 - 3,15 and 2,8
SF-12: 33,33 - 40,16 and 46,22
EQ-5D : 0,44 - 0,537 and 0,599
Oswestry: 56,5 - 50,2 and 47,2
MOS II: 33,58 - 27,38 and 24,58
PGIC: Better: 8; Far better: 11
Conclusions: Fentanyl pectin nasal spray afforded important breakthrough pain relief. This improved
quality of life of patients by allowing a greater degree of mobility, improving self-care and enabling the
realization of simple domestic chores and leisure activities.
483
A COMPARISON OF THE EFFECT OF MORPHINE AND FENTANYL DERIVATIVES ON THE
ANTINOCICEPTION AND BODY TEMPERATURE IN RATS
1
1
1
1
2
3
1
K. Savic Vujovic , S. Vuckovic , D. Srebro , B. Medic , A. Vujovic , D. Obradovic , R. Stojanovic , M.
1
Prostran
1
Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University
2
of Belgrade, Belgrade, Serbia, Hospital for ENT, Clinical Hospital Center 'Dr Dragiša Mišović 3
Dedinje', Belgrade, Serbia, Neurology Clinic, Clinical Center of Serbia, Belgrade, Serbia
Background and aims: In addition to producing antinociception, opioids exert profound effects on
body temperature. This study aimed at comparing antinociceptive and hyperthermic responses
between two groups of µ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine
(phenanthrene-type) derivatives in rats.
Methods: Analgesic activity was assessed by tail-immersion test in male Wistar rats (200-250 g). The
distal 5 cm of the tail was immersed in a warm water bath (55 ±0.5°C) and the time for tail-withdrawal
was measured as a response latency. The body temperature was measured by insertion of a
thermometer probe 5 cm into the colon of unrestrained rats.
Results: Fentanyl (F), (±)cis-3-methyl fentanyl (CM), (±)cis-3-carbomethoxy fentanyl (C), (±)trans-3carbomethoxy fentanyl (T) and (±)cis-3 butyl fentanyl (B) produced dose-dependent increase in
antinociception and hyperthermia. The relative order of analgesic potency was:
CM(11.27)>F(1)>C(0.35)≥T(0.11)≥B (0.056). Similar to this, the relative order of hyperthermic potency
was: CM(8.43)>F(1)>C(0.46)≥T(0.11)≥B(0.076). Morphine (M), oxycodone (O), thebacon (T) and
6,14-Ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-α,α,17-trimethyl-, (5α,7α) (E) also
produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives
the relative order of analgesic potency was: E(56)>O(5)≥T(2.6)>M(1), and similar to this, the relative
order of hyperthermic potency was: E(37)>O(3)≥T(2.3)>M(1).
Conclusion: Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives
produced hyperthermia in rats at doses about 2 times lower, and 6 to 11 times higher, than their
median antinociceptive doses, respectively. This study is first to identify difference between these two
classes of opioid drugs in their potencies in producing hyperthermia.
Supported by Ministry of Education, Science and Technological Development of Serbia (Grant No.
175023).
484
GRT-TA2210, A SELECTIVE NOP RECEPTOR AGONIST, IS ACTIVE IN MOUSE MODELS OF
INFLAMMATORY AND NEUROPATHIC PAIN
K. Linz, T. Christoph, K. Schiene, T. Koch, W. Englberger
Grünenthal GmbH, Grünenthal Innovation, Aachen, Germany
Background and aims: GRT-TA2210 is a new chemical entity displaying selective agonistic activity
at the nociceptin/orphanin FQ (NOP) receptor. The present study investigated its anti-hyperalgesic
and anti-allodynic activity in comparison to the established NOP receptor agonist Ro65-6570.
Methods: GRT-TA2210 and Ro65-6570 were tested in vitro and in mouse models of inflammatory
pain (formalin test) and neuropathic pain (chronic constriction injury, CCI) after intravenous (i.v.),
intrathecal (i.th.), or intracerebroventricular (i.c.v.) administrations.
Results: GRT-TA2210 binds to the NOP receptor with Ki of 0.5 nM. Its affinity to the µ-opioid receptor
is approximately 100 times lower. In a GTPgS assay the compound displayed full agonistic activity at
the NOP receptor.In the formalin test, 1-10 mg/kg i.v. of GRT-TA2210 dose-dependently reduced
hyperalgesia by up to 86% (ED50 = 3.6 mg/kg i.v.). In CCI, GRT-TA2210 reduced cold allodynia
following i.v. (ED50 = 4.5 mg/kg), i.th. (ED50 = 1.2 nmol), and i.c.v. (ED50 = 1.4 nmol) administration.
Anti-hyperalgesic and anti-allodynic activities of GRT-TA2210 were comparable to the effects of
Ro65-6570 in these models. However, while higher doses of Ro65-6570 induced side effects limiting
the dose range in pain models, GRT-TA2210 did not induce any side effects up to the highest tested
doses.
Conclusions: The selective NOP receptor agonist GRT-TA2210 displayed full anti-hyperalgesic
activity in an inflammatory pain model after i.v. administration and a significant anti-allodynic activity in
a neuropathic pain model after i.v., i.th., and i.c.v. administrations. This supports that the NOP system
is important in chronic pain states at different levels of the neuraxis.
485
COMPARATIVE EVALUATION OF THE NOP RECEPTOR AGONIST RO64-6198 IN THERMAL
NOCICEPTION IN RHESUS AND CYNOMOLGUS MONKEYS
1
1
1
2
W. Schröder , K. Linz , K. Schiene , C. Cruz
1
2
Grünenthal GmbH, Grünenthal Innovation, Aachen, Germany, Porsolt Inc., San Antonio, TX, USA
Background and aims: The nociceptin/orphanin FQ peptide (NOP) receptor agonist Ro64-6198 was
reported to produce full thermal antinociception in Rhesus monkeys without side effects. This study
was designed to confirm these findings and to test whether this result also extends to Cynomolgus
monkeys.
Methods: Thermal nociception was assessed in Rhesus and Cynomolgus monkeys using the 50°C
tail dip test. Tail withdrawal latencies (TWL) were determined prior to and at 15, 30, 60, 90, 120, and
150 min after intravenous administration of 0.001, 0.003 and 0.01 mg/kg Ro64-6198. Morphine (3
mg/kg s.c.) and vehicle served as positive and negative controls, respectively. A cutoff of 20 s was
applied to avoid tissue damage.
Results: Ro64-6198 increased baseline TWL (2.0 ± 0.7 s [Rhesus], 4.0 ± 1.5 s [Cynomolgus]) in a
dose- and time-dependent manner with peak effects of 15.8 ± 4.3 s (Rhesus) and 12.5 ± 3.2 s
(Cynomolgus) at 0.003 mg/kg, 30 min post-dose. Antinociceptive efficacy did not increase further at
0.01 mg/kg because of confounding side effects (2/4 Rhesus and 3/4 Cynomolgus monkeys appeared
agitated and hyper-reactive to touch from 30 to 150 min post-dose). Baseline TWL after vehicle
administration as well as antinociceptive effects of Ro64-6198 were not significantly different between
Rhesus and Cynomolgus monkeys, except at 0.01 mg/kg, 150 min post-dose.
Conclusions: Rhesus and Cynomolgus monkeys showed similar sensitivity to thermal nociceptive
stimulation. Antinociceptive efficacy of Ro64-6198 was limited, probably due to side effects at the
highest dose, and did not differ between monkey species.
486
IN VIVO PROFILING OF SEVEN COMMON OPIOID LIGANDS FOR ANTINOCICEPTION,
CONSTIPATION AND RESPIRATORY DEPRESSION: NO TWO HAVE THE SAME PROFILE
1
1
1
M.T. Smith , A. Kuo , B.D. Wyse , W. Meutermans
2
1
Centre for Integrated Preclinical Drug Development & School of Pharmacy, The University of
2
Queensland, Alchemia Ltd, Brisbane, QLD, Australia
Background and aims: We previously showed that the in vitro profiles of seven opioid ligands
(morphine, morphine-6-glucuronide (M6G), fentanyl, oxycodone, buprenorphine, DPDPE and
U69593) are subtly different with no two ligands having the same profile when assessed using the
forskolin stimulated cAMP assay in cells over-expressing single populations of µ, δ or κ-opioid
receptors. Hence, this study assessed whether these in vitro differences translated into betweenopioid differences in their in vivo activity profiles.
Methods: Ethics approval was obtained from The University of Queensland. Male Sprague-Dawley
rats were anaesthetized with xylazine (8 mg/kg i.p.) and zoletil (50 mg/kg i.p.). An
intracerebroventricular (ICV) guide cannula was inserted and rats were kept warm during surgical
recovery. Five days later, rats received single ICV doses of one opioid or vehicle. Antinociception,
constipation and respiratory depression were assessed using the warm water tail flick test, the castor
oil-induced diarrhoea test and whole body plethysmography, respectively.
Results: Single ICV doses of morphine, M6G, fentanyl and oxycodone evoked dose-dependent
antinociception in rats. Buprenorphine was a partial agonist, whereas DPDPE and U69593 evoked
moderate and weak antinociception, respectively. For constipation, M6G, fentanyl, and buprenorphine
evoked dose-dependent effects, oxycodone was a partial agonist, DPDPE and U69593 were inactive
and the morphine dose-response curve was an inverted V-shape. Morphine, M6G, fentanyl and
buprenorphine evoked dose-dependent respiratory depression. Oxycodone was a partial agonist,
whereas DPDPE and U69593 were inactive.
Conclusion: For the seven opioid ligands tested, no two have the same activity profile for
antinociception, constipation and respiratory depression in rats.
487
OPIOIDS AND THE SEROTONIN SYSTEM: HUMAN 5-HT-TRANSPORTERS AND 5-HT-PLASMA
CONCENTRATIONS ARE INFLUENCED BY SPECIFIC OPIOIDS
1,2
3
1
3
2
M. Barann , U.M. Stamer , M. Lyutenska , F. Stüber , H. Bönisch , B.W. Urban
1
1
2
Department of Anaesthesiology and Intensive Care Medicine, Institute for Pharmacology and
3
Toxicology, University of Bonn, Bonn, Germany, Department of Anaesthesiology and Pain Medicine,
Inselspital, University of Bern, Bern, Switzerland
Background and aims: Serotonin (5-HT) plays a role in analgesia and some opioids are known to be
involved in 5-HT toxicity if administered concomitantly with serotonergic drugs. Serotonin receptors
have been ruled out as a target for several opioids at clinically relevant concentrations. As a further
component of the 5-HT system 5-HT-transporters (5-HTT) are now investigated. This study tests
whether opioids and ketamine inhibit the platelet 5-HTT and whether this leads to an increase in free
plasma 5-HT concentrations.
Methods: Effects of opioids, ketamine and citalopram (specific 5-HTT inhibitor; "active control") on
3
the human 5-HTT were quantified by determining the uptake of [ H]5-HT in stably transfected HEK293
cells and by measuring 5-HT concentration in human blood plasma (ELISA).
3
Results: Citalopram (1 µM) completely suppressed [ H]5-HT uptake in HEK293 cells. Citalopram also
prevented 5-HT uptake in platelets after spiking with 100 nM 5-HT. Free 5-HT plasma concentrations
increased by 174%. Tramadol (1-20 µM), pethidine (meperidine; 10-100 µM) and ketamine (30-300
3
µM) also suppressed [ H]5-HT uptake and increased free plasma 5-HT concentration-dependently. In
contrast, morphine, hydromorphone, fentanyl and alfentanil did not change either parameter at
concentrations ≤30 µM.
Conclusions: Opioid effects on the 5-HTT in-vitro and human 5-HT-plasma concentrations were
corresponding: drugs which inhibited 5-HTT in-vitro (tramadol, pethidine, ketamine, but not alfentanil,
fentanyl, hydromorphone, morphine) also caused an increase of free plasma 5-HT by inhibition of 5HT uptake of platelets in blood samples. The effects may contribute to serotonergic effects produced
by opioids and toxicity when given in combination with serotonergic drugs.
488
INTERACTIONS OF OPIOID AND NOCICEPTIN/ORPHANIN-FQ (NOP) RECEPTORS IN ACUTE
HEAT-NOCICEPTION AND DIABETIC HEAT-HYPERALGESIA AS REVEALED IN OPIOID/NOPRECEPTOR KNOCK-OUT MICE
1
1
2
1
T. Christoph , T. Koch , T.M. Tzschentke , B.Y. Kögel , K. Schiene
1
1
2
Grünenthal GmbH, Grünenthal Innovation, Global Research and Development, Department of
Pharmacology, Grünenthal GmbH, Aachen, Germany
Background and aims: µ-opioid receptor (MOP) agonists are standard analgesics for moderate to
severe pain conditions. Their use is limited by side effects. Two other opioid receptors, δ (DOP), and κ
(KOP), and the nociceptin/orphanin FQ (NOP) receptor have been cloned and are known to interact in
various ways. The interaction of these receptors was investigated in mouse pain models.
Methods: MOP, DOP, KOP and NOP receptor knock-out and congenic wild-type mice were tested for
acute heat nociception in naïve animals, and for heat hyperalgesia in streptozotocin-treated diabetic
animals. Reference agonists morphine (MOP), SNC-80 (DOP), U50488H (KOP) and Ro65-6570
(NOP) or vehicle were administered intraperitoneally.
Results: In wild-type mice, 60-100% antinociceptive and antihyperalgesic efficacy was reached with
similar (morphine: 10; 10) or different (SNC80: no effect up to 10; 3.16; U50488: 21.5; 3.16; Ro656570: 1; 0.1) doses (mg/kg). While the respective agonists showed lack of efficacy in the
corresponding knock-out strains, clear attenuation of efficacy was also seen in heterologous knockouts. Only morphine showed full efficacy in heterologous knock-outs. The interaction appeared to be
most prominent for KOP-DOP and NOP-DOP receptors in heat hyperalgesia. For example, although
the DOP agonist was ineffective in heat nociception, an interaction with KOP receptors is suggested
by reduced KOP agonist efficacy in DOP receptor knock-outs. Furthermore, while morphine
equipotently inhibited acute and chronic pain, all other agonists showed a higher potency against heat
hyperalgesia.
Conclusions: The observation that heterologous knock-out affected the response to selective ligands
suggests an interaction between the respective receptor types.
489
ANTINOCICEPTIVE, ANTIHYPERALGESIC AND ANTIALLODYNIC ACTIVITY OF THE NOP
RECEPTOR AGONIST RO65-6570 IN RODENT MODELS OF PAIN
1
1
1
K. Schiene , T. Christoph , B.Y. Kögel , T.M. Tzschentke
1
2
2
Grünenthal GmbH, Grünenthal Innovation, Global Research and Development, Department of
Pharmacology, Grünenthal GmbH, Aachen, Germany
Background and aims: The nociceptin/orphanin FQ (NOP) system plays a significant role in pain
conditions. The aim of this study was to examine the antinociceptive, antiallodynic and
antihyperalgesic effect of the NOP receptor agonist Ro65-6570.
Methods: Ro65-6570 was tested in different animal models of acute, inflammatory, visceral and
neuropathic pain after systemic (intravenous, i.v. and intraperitoneal, i.p.) administration in rats and
mice.
Results: In the rat tail-flick test, Ro65-6750 showed full efficacy at 681µg/kg. In the rat formalin test,
Ro65-6570 had moderate but significant antinociceptive efficacy (21% at 313µg/kg i.v.). In rat CFAinduced paw inflammation, Ro65-6570 also showed moderate antihyperalgesic efficacy (16% at
316µg/kg i.v.). In mouse mustard oil colitis, Ro65-6750 completely abolished spontaneous pain
behavior (at 215µg/kg) and reduced referred tactile hyperalgesia and allodynia. In chronic constriction
injury in mice, Ro65-6570 reduced cold allodynia (39% at 316µg/kg i.v.), and reduced heat
hyperalgesia in streptozotocin-induced diabetic neuropathy in mice (84% at 100µg/kg i.p.). In the rat
spinal nerve ligation and streptozotocin-models, Ro65-6579 showed an effect of 66% (200µg/kg i.v.)
and 33% (316µg/kg i.v.), respectively. In all pain models, Ro65-6570 was tested up to the highest
dose without overt side effects. Doses below 1mg/kg (i.v.) were shown to be without confounding
locomotor side-effects in naïve rats. In mice, doses below 1mg/kg i.p. did not affect exploratory
activity.
Conclusions: Ro65-6570 was active across different pain models, with effects being most
pronounced in models of visceral and neuropathic pain. This validates the NOP-receptor as an
important pain target.
490
PERIPHERAL MECHANISMS OF ELECTROACUPUNCTURE IN RELIEVING INFLAMMATORY
HYPERALGESIA
1
1
2
3
1
1
1
Y. Wang , R. Truemper , S. Mousa , F. Peng , D. Hackel , H. Rittner , A. Brack , Molecular Pain
Research Group
1
2
Department of Anesthesiology, University Hospital of Würzburg, Wuerzburg, Department of
3
Anesthesiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Department
of Computer Science, University of Applied Sciences, Augsburg, Germany
Background and aims: Endogenous opioid peptides like Met-enkephalin (ENK), beta-endorphin
(END) and dynorphin (DYN) are produced by leukocytes infiltrating inflammatory tissue in humans
and animals. Release of endogenous opioid peptides and binding to opioid receptors leads to
peripheral endogenous analgesia. In CFA inflammation neutrophils are the major producers of opioid
peptides in early inflammation while later macrophages and T cells are responsible. Previous studies
have shown that electroacupuncture (EA) could inhibit inflammatory hyperalgesia at different phases
of CFA inflammation. In this study we aimed to establish a reproducible model of EA treatment and to
elucidate anti-hyperalgesic mechanisms at late phase (96 h) of CFA-induced inflammatory
hyperalgesia.
Results:
1. EA elicited sustained thermal and mechanical analgesia in CFA inflammation up to 144 h post
CFA.
2. Thermal or mechanical antinociception produced by EA at late phase (96 h) post CFA was
mediated by peripheral opioid receptors and opioid peptides.
3. EA significantly attenuated CFA evoked inflammation.
4. Cytokine expression patterns were altered by EA, including upregulation of specific local analgesic
mediators as well as inhibition of certain inflammatory cytokines.
Conclusions: EA suppresses inflammatory hyperalgesia via increasing the local opioid peptide
release and changes in cytokines expression patterns at late phase (96 h) of CFA-induced local
inflammatory hyperalgesia.
Reference:
1. Wang Y et al. Eur J Pain. 2013 May 6. doi: 10.1002/j.1532-2149 2. Rittner, H.L. et al. (2009). Plos
Pathogens 5, e1000362.
491
INDIVIDUALIZED PHARMACOTHERAPY OF CANCER- RELATED PAIN IMPROVES EFFICACY
AND SAFETY
J. Woroń, I. Filipczak- Bryniarska, J. Wordliczek
Dept of Clinical Pharmacology and Dept. of Pain Medicine and Palliative Care, Jagiellonian University
College of Medicine, Krakow, Poland
In the current pharmacotherapy to strive for individualized treatment, which should include both the
pathogenesis and the intensity of pain and its location. Except that you should take into account the
age of the patient´s pharmacogenetic aspects, co-morbidities and other concomitant treatment that
may be included in any potential adverse interactions with analgesics. To apply adequate to the
intensity of pain dose titration is recommended therapeutic dose so that it showed maximum efficiency
while minimizing the risk of drug-induced side effects. The study compared the effectiveness of
pharmacological pain in two groups of patients counting on 50 people, where one performed the
procedure necessary to individualize therapy, in the second decision to use drugs was not preceded
by a clinical analysis of factors that are described in the introduction, and which have an impact on the
effectiveness and tolerance of treatment. In the group in which no individualized therapy until the 32
(64%) cases occurred ineffective mastery of pain or are side effects of analgesics that forced a
change of the treatment, while that of individualized therapy in only 3 (6%) cases, it was necessary to
change medications because of unsatisfactory analgesic efficacy or the appearance of side effects.
due to the fact that, in practice, should individualize analgesic action.
492
ARE HIGH-DOSE COMBINED ORAL OXYCODONE / NALOXONE ARE EFFECTIVE AND SAFE IN
PATIENTS WITH PAIN ASSOCIATED WITH CANCER?
J. Woroń, I. Filipczak-Bryniarska, K. Krzanowska, J. Wordliczek
Dept of Clinical Pharmacology and Dept. of Pain Medicine and Palliative Care, Jagiellonian University
College of Medicine, Krakow, Poland
Combination of oxycodone with naloxone used by oral under the trade name Targin is an effective
connection in patients in whom an optimal analgesia interfere with existing constipation. according to
a summary of product characteristics of the drug Targin, the maximum dose which can be used daily
to 80 mg of oxycodone combined with 40 mg naloxone. Makes it difficult to treat patients whose daily
dose of more than 80 mg oxycodone, while constipation often appear resistant to laxatives. In our
work, we describe five patients in whom the need for oxycodone was higher than 80 mg per day, and
at the same time were difficult to control constipation. In three cases, oxycodone is used because of
pain associated with pancreatic cancer, and in one case it was cancer of the bladder and prostate
cancer 1. In all cases due to the visceral pain that occurs is used as the selection opioid oxycodone.
Rotation as the Targin was a consequence of constipation, which prevented continuation of analgesic
therapy. Targin minimum dose used in these cases was 240 mg oxycodone and 120mg naloxone,
whereas the maximum 540 mg oxycodone and 270 mgnaloxone. In all cases, we observed the same
as the level of analgesia as with oxycodone alone and significantly reduced the intensity of the
measured index BFI constipation. In our opinion high Connection dose of oxycodone with naloxone
are effective and do not cause adverse reactions or turn away analgesia induced by opioids.
493
THE ROLE OF PAIN ANTICIPATION IN A VISCERAL NOCEBO PARADIGM: A RESPONDER
ANALYSIS IN HEALTHY SUBJECTS EXPECTING PAIN SENSITIZATION
1
2
1
2
3
1
J. Schmid , N. Theysohn , C. Mewes , C. Gramsch , E.R. Gizewski , S. Elsenbruch , S. Benson
1
1
2
Institute of Medical Psychology and Behavioral Immunobiology, Institute of Diagnostic &
Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg3
Essen, Essen, Germany, Clinic of Neuroradiology, Medical University of Innsbruck, Innsbruck,
Austria
Background and aim: We implemented a nocebo paradigm that does not involve the administration
of an inert substance but rather negative expectations of increased visceral pain due to sensitization.
Methods: Eighteen volunteers underwent consecutive fMRI sessions during which cued painful rectal
distensions were delivered. To induce an expectation of increasing pain across sessions (nocebo
response) subjects were instructed to expect pain sensitization (although in reality habituation is
seen). For analysis, a median split based on expectation of pain was performed to compare
responders and non-responders using ANOVA (behavioral data) and two-sample t-tests (BOLD
whole-brain analysis, p < .001 uncorrected).
Results: Nocebo responders not only revealed higher expectation of pain prior to painful stimulation,
but also greater pain ratings, anxiety and arousal when compared to non-responders (all p < .01).
Responders also demonstrated significantly greater activation during anticipation in right insula
compared to non-responders. Against our expectation, no group differences were observed for the
pain delivery phase.
Conclusion: Nocebo effects can be induced even in the absence of administration of an inert
substance. Our results support the role of anticipation in mediating nocebo effects in visceral pain.
These findings have implications for the pathophysiology of IBS, but need replication and extension in
larger samples.
494
PARADOXICAL SLEEP DEPRIVATION INCREASES PLACEBO ANALGESIA: AN
EXPERIMENTAL CONTROLLED POLYGRAPHIC SLEEP STUDY
1,2
3
1
F. Chouchou , J.-M. Chauny , P. Rainville , G. Lavigne
1
1,2
2
Faculties of Dental Medicine and Medicine, Université de Montréal, Center for Advanced Research
3
in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Trauma and Emergency Units, Surgery
Department, Hôpital du Sacré-Cœur de Montréal, Montreal, QC, Canada
Background and aims: Paradoxical sleep (PS) has been recently associated with a reduction in
expectation-mediated placebo effects that might reflect a sleep-dependent reprocessing of
expectations. The objective of our study was to assess whether selective paradoxical sleep
deprivation (PSD) could raise expectations of relief and placebo analgesia the next morning.
Methods: Twenty six healthy subjects slept in the laboratory and were double-blind randomized into
two groups: a control group (placebo) and an experimental group deprived from PS (0.3 mg clonidine
p.o.). Subjects were submitted to a placebo analgesic conditioning in the evening wherein the
intensity of the painful stimulation was surreptitiously reduced after the application of an inert cream.
Expectations and placebo analgesia were measured in the next morning.
Results: The sleep analysis showed that duration of PS (p< 0.001) is strongly reduced whereas
duration of stage 2 (p< 0.001) was increased in the PSD group in comparison to control group.
Although the expectations of relief was similar between groups (p=0.927), a higher level of placebo
analgesia was observed in PSD subjects (p=0.006). Placebo analgesia correlated positively and more
strongly with relief expectation in the PSD group (r=0.91, p=0.005) than the control group (r=0.54,
p=0.152; PSD vs. control group: p=0.039).
Conclusion: These results support the role of PS in the reprocessing of analgesic expectations which
may lead to a reduction of expectation-induced placebo effects. This study has important implications
for the understanding of sleep-dependent learning processes and the improvement of clinical pain
relief (FC is a FRSQ-RSBO fellow).
495
PREDICTORS OF PLACEBO ANALGESIA ACROSS MULTIPLE CENTRES
1
2
3
1
4
5
B. Horing , U. Bingel , S. Elsenbruch , P. Enck , H. Flor , R. Klinger , B. Doering
6
1
Internal Medicine VI - Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen,
2
Tübingen, Department of Neurology, University Medical Center Hamburg Eppendorf, Hamburg,
3
Institute of Medical Psychology & Behavioral Immunobiology, Essen University Hospital, Essen,
4
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical
5
Faculty Mannheim, Heidelberg University, Mannheim, Department of Psychology, Outpatient Clinic of
6
Behavior Therapy, University of Hamburg, Hamburg, Department of Clinical Psychology and
Psychotherapy, Universität of Marburg, Marburg, Germany
Background and aims: Placebo mechanisms in pain are increasingly well understood, but the
determinants of placebo responsiveness have remained obscure: Among psychosocial predictors,
findings are rarely replicated, and adequate control groups are often omitted. In this post-hoc
analysis, we attempted to identify placebo analgesia predictors with a meta-regressional approach
involving patients/volunteers from different study centres of a trans-national centre grant.
Methods: Prerequesite for inclusion was the use of a VAS for pain intensity; otherwise, studies
showed heterogeneity in terms of paradigms, pain modalities, and study populations. From a pool of
possible predictors, only eight achieved sufficient N for inclusion: age, trait anxiety, and subscales of
the Beliefs about Medicine Questionnaire (BMQ). Exploratory correlational analyses were performed.
Subsequently, predictors were entered into single moderator analyses, i.e. linear regressions
including interaction terms of the categorical predictor “placebo group” versus “no-treatment control
group”, with an average sample size of N=162.
Results: Significant correlations were discovered in the placebo group but not the control group:
BMQ subscales medicine harms and medicine is beneficial were positively correlated with symptom
reduction after placebo (r=.20, r=.23), BMQ illness-specific concerns correlated negatively (r=-.24). In
the regression analyses, the only differential predictor was the BMQ scale medicine is beneficial
(beta=.37, r²=.17).
Conclusion: Dispositional belief in the positive efficacy of medical treatment in general can partially
account for the amount of response to placebo. Moderator analyses involving heterogeneous studies
are feasible. Several pitfalls of inter-study-analyses can be delineated. (Supported by a trans-national
centre grant from Deutsche Forschungsgemeinschaft, FOR 1328).
496
PLACEBO ANALGESIA EFFECT SIZES DIFFER SIGNIFICANTLY DEPENDING ON WAYS OF
ESTIMATION
1
2
2
1
K. Lund , L. Vase , G.L. Petersen , T.S. Jensen , N.B. Finnerup
1
1
2
Danish Pain Research Center, Aarhus University Hospital, Aarhus C, Department of Psychology,
School of Business and Social Sciences, Aarhus University, Aarhus, Denmark
Background and aim: Placebo effects have traditionally been calculated as the difference between
placebo treatments and no treatments. Recently, placebo effects have also been investigated via
open vs hidden administrations of active treatments. So far no studies have directly compared these
two types of placebo effects within the same study.
Methods: In an experimental BTPD, 46 healthy volunteers received four injections with hypertonic
saline (HS, 5%) in the masseter muscle. Pain intensity was registered on a continuous electronic
visual analogue scale. Two injections were given with HS alone: one with verbal suggestions for pain
relief (placebo) and one without (control). Another two injections included HS along with lidocaine
(1%): one was open (the subjects were aware of the administration of an analgesic) and one was
3
hidden. Primary outcome measure was pain intensity measured as area under the curve (AUC, mm ).
Results: Placebo effects were significant in the traditional paradigm (mean placebo AUC 1626 (SD
2315) (p< 0.001)) as well as in the open vs hidden paradigm (mean placebo AUC 801 (SD 2177),
(p=0.016)) Furthermore, there was a significant difference between the two approaches to the
placebo effect (p=0.049).
Conclusions: The magnitude of placebo effects differs significantly depending on the way in which
the placebo effect is conceptualized and estimated. In this study the open vs hidden paradigm
showed a smaller placebo effect than the traditional paradigm. Further analyses of psychological data
will be presented at the congress.
Acknowledgements: This study is part of the Innovative Medicine Initiative project EUROPAIN,
www.imi.europa.eu.
497
THE ROLE OF METACOGNITIVE FUNCTIONS IN PLACEBO ANALGESIA: AN ACTIVATION
LIKELIHOOD ESTIMATION META-ANALYSIS
1
S. Palermo , M. Amanzio
1
1,2
2
Department of Psychology, University of Turin, National Institute Neuroscience, Turin, Italy
Background and aims: Understanding placebo analgesia (PA) by studying the neuropsychologicalrelated-network modulated by expectation is an endeavour that has strong clinical implications.
Indeed a patient´s expectancy of improvement influences outcomes in placebo response. Up till now
we have a limited understanding of the neuropsychological factors that influence patients' response to
placebo treatment. We recently used Activation Likelihood Estimation meta-analysis (ALE) to search
for the cortical areas involved in PA in human experimental pain models. The expectation-placeborelated analgesic mechanisms were found in the left anterior cingulate, right precentral, lateral
prefrontal cortex and in the left periaqueductal gray (Amanzio et al., 2013). Since anterior cingulate is
part of the medial prefrontal cortex (MPFC), it would be interesting to study the role of executivemetacognitive functions in PA and the functional network on the basis of this phenomenon.
Methods: Following a forward inference between PA in human experimental pain and selected
metacognitive functions (monitoring, response-inhibition and set-shifting), we used focused ALE metaanalysis to estimate related consistent activation. To test whether these results differed statistically,
we performed subtraction analyses using a contrast studies procedure.
Results: We found an effective overlap between these two functional networks with a particularly
important role of MPFC, thus emphasizing the relation between PA and metacognitive functions.
Conclusions: Our results demonstrate how the PA response arises as a result of cognitive abilities
emphasizing the role of specific metacognitive functions in order to achieve a more comprehensive
approach compared to previous studies in this field.
498
VISCERAL PLACEBO ANALGESIA IN IRRITABLE BOWEL SYNDROME PATIENTS,
INFLAMMATORY BOWEL DISEASE PATIENTS, AND HEALTHY SUBJECTS
1
1,2
1
2
3
J. Schmid , F. Gass , S. Benson , J. Langhorst , E. Gizewski , S. Elsenbruch
1
1
Institut of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of
2
Duisburg-Essen, Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, University of
3
Duisburg-Essen, Essen, Germany, Department of Neuroradiology, Innsbruck Medical University,
Innsbruck, Austria
Background and aims: Although the relevance of placebo effects is well-established, comparatively
little experimental evidence exists in the context of visceral pain. We studied behavioural and neural
responses of expectation-induced placebo analgesia in two patient populations with chronic
abdominal pain, i.e., irritable bowel syndrome (IBS; N=17) and ulcerative colitis (UC; N=15), each
compared to healthy controls (N=17).
Methods: Participants underwent three fMRI sessions during which cued painful rectal distensions
were delivered. After an adaptation session, two conditions with specific instruction followed: In one
condition, subjects received a clearly marked saline solution, whereas in the other condition they were
deceptively told that a potent painkiller was given. The conditions were carried out in counterbalanced
order. State anxiety, tension and expected pain intensity were assessed prior to each session.
Perceived pain intensity was assessed with online ratings.
Results: Within-group analyses revealed significant placebo-induced pain reduction in all three
groups (paired t-tests: IBS: p=.014; Colitis: p=.003, healthy subjects: p=.002). Expected pain intensity
was reduced in all three groups, but only reached statistical significance within IBS patients (p< .001).
No significant reductions in state anxiety or arousal were observed. Between-group comparisons
revealed a significantly reduced placebo response for perceived pain intensity in IBS patients
compared to healthy controls (p=.04).
Conclusion: Patients with chronic abdominal pain due to either a functional or an inflammatory
gastrointestinal condition show visceral placebo analgesia based on suggestions. This response may
be diminished in IBS which is relevant within a bio-psycho-social conceptualization of this condition.
499
PLACEBO ANALGESIA IN CHILDREN AND ADOLESCENTS - AN FMRI STUDY
1
2
2
1
2
N. Wrobel , T. Fadai , C. Sprenger , C. Ritter , S. Brassen , U. Bingel
1
1
2
Department of Neurology, Department of Systems Neuroscience, University Medical Center
Hamburg-Eppendorf, Hamburg, Germany
Placebo analgesia is a prime example of endogenous pain modulation. Clinical studies suggest that
children may have larger placebo responses than adults. However, these studies can not distinguish
whether age-related differences in the underlying disease (e.g. migraine attack) or differences in
placebo responsiveness explain the righ placebo rates in clinical trials in children. Here we used an
established experimental placebo analgesia paradigm involving expectancy and conditioning
components to investigate placebo responses and their underlying mechanisms in healthy children
and adults.
25 healthy children and adolescents (M=13.5 ± 0.2 SEM years) and 23 healthy adults (M=27 ± 0.8
SEM years) were included in this study.
A significant placebo response was elicited in children and adults(Δ VAS rating [control - placebo]
M(children)=6.35, SEM=2.5; M(adults)=5.45, SEM=2.4). No difference was observed in the placebo
analgesic response between the two groups. However, children showed a significantly stronger
correlation between the Δ VAS ratings in the conditioning and test phase compared to adults
(rchildren=0.4, radults=-0.2, z=2.06, p=0.02).
The results of the fMRI analysis will be reported at the poster.
Our results do not support the notion of a stronger placebo response in children compared to adults.
We did observe a correlation between pain reduction during the conditioning phase with the later
placebo response in children suggesting that treatment experience strongly influences later treatment
outcomes. Both these findings have important implications for clinical care of children and emphasize
the need for systematic, evidence-based treatment approaches and prevention of unnecessary
treatment failure in children.
500
A SENSORY NEURON SPECIFIC GCAMP3 REPORTER MOUSE FOR IMAGING OF PRIMARY
AFFERENT CENTRAL TERMINALS IN SPINAL CORD
D. Guo, J. Hu
Centre for Integrative Neuroscience (CIN) / University of Tübingen, Tübingen, Germany
Background and aims: Synaptic plasticity does not only occur during learning and memory, but also
under many pathological situations, such as chronic pain. Most studies on synaptic plasticity focused
on post-synaptic function because of lack of techniques to investigate pre-synaptic function directly.
Therefore, we have designed a primary sensory neuron specific GCaMP3 reporter mouse line for
unambiguous imaging of primary afferent central terminals in spinal cord.
Methods: Advillin-GCaMP3 mice were generated by crossing Ai38 mice, which has a GCaMP3 gene
following a loxP-flanked STOP cassette, with mice expressing Cre recombinase under the regulatory
elements of sensory neuron specific Advillin gene. Offsprings from this breeding carried both
GCaMP3 gene and Cre recombinase expressed the fluorescent calcium indicator protein, GCaMP3,
exclusively in sensory neurons.
2-photon imaging was performed on spinal cord slices and whole DRG tissues to detect GCaMP3
+
fluorescence signal. High [K ] solution perfusion and electrical stimulation were applied to induce
2+
neuron firing, and examine GCaMP3's ability to respond to the consequent Ca influx.
To study the pre-synaptic activity changes, nerve injured mice were used.
Results: Fluorescence was only detected in DRGs and in white matter of spinal cord dorsal horns,
+
where presynaptic terminals innervate. Neuronal activity was observed in these areas after high [K ]
solution perfusion or electrical stimulus.
Conclusions: Our calcium imaging data on whole DRG tissues and spinal cord slices showed that
the Advillin-GCaMP3 mouse is an ideal tool for studying the pre-synaptic activity changes in live
tissues after tissue or nerve injury.
782
PAIN PROGRESSION IN KNEE OSTEOARTHRITIS: ASSOCIATIONS WITH MORPHOLOGICAL
BRAIN CHANGES
1,2
2,3
2,3
1
H. Alshuft , T. Kurien , B. Scammell , R. Dineen , D. Auer
1
1,2
2
3
Radiological and Imaging Sciences, University of Nottingham, Arthritis Research UK, Bone and
Joint Research Group, Orthopaedic and Accident Surgery, University of Nottingham, Nottingham, UK
Background and aims: Pain duration as a predictor of structural brain changes has been
controversial among different neuroimaging chronic pain studies. We previously found a significant
time-dependant cortical thinning in several brain areas in a cohort of knee OA patients. In this study
we contrast the association between shorter- and longer-pain groups in reference to age and gender
matched healthy controls
Methods: 30 patients with chronic knee-OA pain (1-38years) but no other major co-morbidities were
median-split (8.5years) into short (63.7±10.1 M±SD, 7males) and long (66.3±10.1 M±SD, 9males)
pain duration. 15 age and gender matched healthy controls (59.9±6.6 M±SD, 5males). All participants
underwent 3D brain scans using GE 3T-MRI and 32-channel head-coil. Informed consent was
obtained. Nottingham-REC2 approved the study.
Cortical thickness was estimated using FreeSurfer (http://surfer.nmr.mgh.harvard.edu/). Regions of
interest (ROIs); bilateral precuneus, bilateral inferior-parietal, Lt. superior-temporal and Rt. Rostralfrontal were predefined from our previous findings. ANOVA and post-hoc analyses were used to test
mean differences, P< 0.05.
Results: Compared to HC, long-pain group showed thinner cortex in all ROIs except Rt. Precuneus
and Rt. Rostral-frontal, whereas short-pain group had only thinner Rt. Precuneus.
Longer vs. shorter revealed thinner cortex in the long-pain group in all except Lt. inferior-parietal and
Rt. Precuneus.
Conclusion: Our results suggest that pain-related changes in cortical thickness cumulate over pain
duration and indicate a late stage of chronic pain. Longitudinal studies are required to investigate the
reversibility of theses changes and to test weather incurable chronic pain can be explained by
irreversibility of these changes.
783
STUDYING THE BRAIN SIGNATURE IN CHRONIC PAIN: A SYSTEMATIC REVIEW AND METAANALYSIS OF 146 PAIN FMRI EXPERIMENTS
1
1,2
1
1,2
R. Tanasescu , W.J. Cottam , C.R. Tench , D. Auer
1
2
Division of Clinical Neuroscience, Arthritis Research UK Pain Centre, University of Nottingham,
Nottingham, UK
Background: The aim of this study was to perform a systematic review and meta-analysis of
cutaneous nociceptive brain activation in chronic pain patients (CPP) compared to healthy subjects
(HC) in fMRI experiments.
Methods: 94 nociceptive fMRI studies were included (27 experiments in 280 CPP, 119 experiments
in 1545 HC). LocalALE (an in-house toolbox) was used to estimate, synthesize and compare ALE
from reported activation foci (MA-A), their contrasts (MA-AC) and where available from reported
contrasts (MA-C). Significance level was set at p< 0.05, false cluster detection rate corrected.
Results: MA-A: Reported activations show convergent activation in the insula (INS), anterior
cingulate (ACC) and secondary somatosensory cortices (S2) for all groups and stimuli except for the
low mood condition. MA-AC: The pattern of activation likelihood did not differ between CPP and HC
regardless of modality, but there was a modality effect in CPP (increased S2, decreased thalamic
activation for mechanical vs. thermal). Thermal hyperalgesia increased prefrontal activation in HC.
MA-C confirmed the increased prefrontal activation in thermal hyperalgesia and also revealed a
mechanical hyperalgesia effect (increase in ACC, right INS, left S2), and showed a disease effect for
mechanical pain (increase in ACC).
Conclusion: Published data in chronic pain does not support consistent shift in nociceptive brain
activation nor strong generalised central sensitisation. The subgroup of studies reporting disease
contrasts however suggests altered pain processing with increased ACC activation in response to
mechanical pain.
784
A PUTATIVE NITROUS OXIDE ANALGESIA MECHANISM: A RESTING STATE FMRI STUDY IN
HEALTHY VOLUNTEERS
1,2
3
3
N. Dashdorj , K. Corrie , R.P. Mahajan , D.P. Auer
1,2
1
Division of Radiological and Imaging Sciences, School of Clinical Sciences, University of Nottingham,
3
Arthritis Research UK Pain Centre, University of Nottingham, Division of Anaesthesia and Intensive
Care, School of Clinical Sciences, University of Nottingham, Nottingham, UK
2
Background and aims: Nitrous oxide (N2O) in a subanaesthetic dose has well-established analgesic
effect both in humans and animals. N2O is thought to modulate pain processing by inducing release of
opioid peptides in periaqueductal grey area. In this study we aim to investigate functional connectivity
alterations in central pain processing pathways following 30% N 2O administrations in healthy subjects.
Methods: Brain network was studied using low frequency BOLD fluctuation from resting state fMRI
acquired at 3T in 19 healthy volunteers undergoing three inhalation conditions (medical air, oxygenenriched medical air (40% oxygen), and 30% N2O with oxygen-enriched medical air (40% oxygen)).
Results: Inhalation of 30% N2O in 40% oxygen, but not 40% oxygen alone, significantly increased the
connectivity of default mode network (DMN) with the parts of executive control network (ECN) and the
salience network connectivity with posterior DMN was greater. In addition, rACC seed-based
connectivity revealed that N2O induced an increase in connectivity with the left supramarginal gyrus,
reduced connectivity within the rACC itself and with the right thalamus. These changes were not
accompanied by BOLD amplitude changes.
Conclusions: This study demonstrates that 30% N2O in oxygen enriched air (40% oxygen)
significantly alters the baseline brain network dynamics. This may reflect analgesic effects of nitrous
oxide, but could also be related to additional anxiolytic properties.
785
STRUCTURAL BRAIN ALTERATIONS IN INDIVIDUALS WITH CHRONIC PAIN
M. de Kruijf, D. Bos, F.J.P.M. Huijgen, A. Hofman, M.W. Vernooij, A.G. Uitterlinden, M.A. Ikram,
J.B.J. van Meurs
Erasmus MC, Rotterdam, The Netherlands
Background: Experienced pain severity not always reflects the extent of pathology. Identification of
brain areas involved in chronic pain could provide insight in these discrepancies. Previously, structural
brain alterations in chronic pain were investigated in case-control studies. We examined structural
brain alterations in a large population-based study, using state-of-the art tools for brainsegmentation.
Methods: In the Rotterdam study, a prospective population-based cohort study of individuals 45yrs
and over, 3967 subjects underwent brain MRI. Brain volumes are segmented and quantified in
millilitres. Chronic pain is defined as pain in at least one site for at least half of the days in the last six
weeks.
We studied total grey and white matter and the four main lobes. Next, we investigated limbic system
and signal-processing structures(hippocampus, amygdala, thalamus and caudate). For analysis,
volumes were Z-score normalised, gender stratified and adjusted for intracranial volume, age and
depression.
Results: In 1527 males and 1856 females, MRI and pain data were available. Chronic pain was
present 27% in males versus 42% in females.
Grey matter volume was smaller in females with chronic pain (Beta=-0.06; P=0.031), mostly in the
temporal lobe (Beta=-0.08; P=0.011) and hippocampus in females (Beta=-0.10; P=0.003). In males
with chronic pain, the amygdala was larger (Beta=0.09;P=0.036).
Conclusions: Females with chronic pain have smaller grey matter volume, specifically in the
temporal lobe and hippocampus. In males, the amygdala is larger in chronic pain.
These findings indicate sexually dimorphic handling and emotional processing of pain, which might be
important in personalized gender-specific pain treatment.
786
AUDITORY BINAURAL BEAT ENTRAINMENT REDUCES BEHAVIOURAL AND
ELECTROPHYSIOLOGICAL RESPONSES TO PAIN
K. Ecsy, C. Brown, A.K.P. Jones
Human Pain Research Group, University of Manchester, Manchester, UK
Background and aims: It has previously been well established that brain oscillatory alpha power (812Hz) is reduced when we experience pain. There appears to be a negative correlation between
alpha power, and both the behavioural and electrophysiological responses to acute pain. Increasing
alpha power could hence decrease pain ratings and the amplitude of laser-evoked potentials,
measurable through electroencephalography (EEG). Oscillatory frequencies can be modulated by
auditory entrainment, where brainwave frequencies adapt to the rhythm at which they are being
stimulated.
The aim of this study was to determine whether 10 minutes of auditory entrainment at 8 Hz, 10Hz and
12Hz will affect the volunteers' pain perception of the acute heat laser stimulus, compared to the white
noise control.
Methods: Each volunteer (n=12) was asked to attend two visits, one randomly allocated control
session and one entrainment session. During the entrainment session, baseline electrophysiological
and behavioural responses to the heat laser induced painful stimulation were compared to pain
responses after a 10 minute 8Hz, 10Hz, and 12Hz binaural beat entrainment. The control session had
an almost identical set up, with white noise replacing alpha.
Results: Both the behavioural pain ratings and laser evoked responses were significantly reduced
compared to control after the 8Hz and 10Hz entrainment. No significant difference was found after the
12Hz entrainment.
Conclusions: Auditory entrainment at low alpha frequencies can successfully reduce the perception
of acute pain. These results are in line with previous findings demonstrating opposite effects of low
and high alpha frequencies on pain perception.
787
IMAGING PAIN ANTICIPATION AND PAIN PERCEPTION IN DRUG-NAÏVE PATIENTS WITH
IDIOPATHIC PARKINSON'S DISEASE
K. Forkmann, W. Grashorn, K. Schmidt, C. Buhmann, U. Bingel
Department of Neurology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Background: Pain is a frequent but often neglected non-motor symptom of Parkinson's disease (PD).
It's prevalence in PD seems to be increased compared to other neurodegenerative diseases and agematched healthy adults. The neuronal mechanisms underlying pain in PD are far from being
understood. Alterations in central processing or a dysfunction of the descending pain control are
hypothesized to explain the high frequency of pain symptoms in PD.
Method: In this study we investigated brain mechanisms associated with the anticipation and
perception of pain in PD. To this aim, we used a well-established fMRI paradigm in which we applied
15 individually calibrated heat stimuli to the subjects' left volar forearm. Controls and PD patients were
asked to give an intensity rating for each stimulus on a visual analogue scale [VAS 0-100]. This study
was approved by the local ethics committee. 23 PD patients (Hoehn&Yahr 1-2, 12 male, age, M±SD =
64.9±9.6) and 22 healthy controls (matched in age, gender, education; 12 male, age, M±SD =
64.9±8.3) were enrolled in this study. Patients were drug-naïve and have never been treated with
dopaminergic medication in order to avoid confounding drug effects.
Results: PD patients and controls did not differ in their heat pain thresholds (M±SD, 45.5±2.0 °C),
temperatures applied (M±SD, 46.1±1.4 °C), and mean pain intensity ratings (VAS: M±SD, 63.6±13.5;
all t < 1.0). As we completed data collection of this unique patient sample only recently, the analyses
of functional data is still in progress and will be presented on the poster.
788
DIFFERENT LEVELS OF FUNCTIONAL CONNECTIVITY DURING THE CORTICAL PROCESSING
OF PAIN AND ITCH
H.O. Handwerker, C. Forster, V. Vierow
Physiologie & Pathophysiologie, FAU Erlangen/Nürnberg, Erlangen, Germany
Many imaging studies on the cortical processing of sensory input have been performed. A lot of them
focused on pain and some on itch. Interestingly, most of these studies described more or less the
same pattern of brain regions to be involved, independently from the type of the applied stimulus. This
raises the question how a particular pain or itch sensation is generated within these brain areas. Our
hypothesis was that the modality of a sensation is represented by the functional connectivity within
the affected brain regions.
Methods and results: Tonic pain which was induced by squeezing an inter-digital web of the left
hand three times for two minutes. Itch was induced by iontophoretic application of histamine.
Standard fMRI sequences were used to record cortical BOLD signals. BOLD time courses obtained
during the stimulations were extracted from brain regions of interest (ROI) and were correlated to
selected seed regions.
Functional connectivity was more pronounced during pain than during itch. This effect was more
prominent within the lateral system and the thalamus. Less synchronicity was found between regions
of the lateral system and the medial system or frontal areas, respectively, during both stimulation
conditions.
Conclusions: Higher values of functional connectivity during pain are a sign of highly synchronized
activity during pain and less during itch. The level of synchronicity between the brain regions which
are involved in the processing of a sensory input could be a potential source to associate a sensation
with certain quality like pain or itch.
789
QUANTITATIVE ASSESSMENT OF THE RELIABILITY OF PERFUSION MRI AND VISUAL
ANALOGUE SCALE IN A CLINICAL MODEL OF ON-GOING POST-SURGICAL PAIN
1
1,2
3
3
1
1
D.J. Hodkinson , K. Krause , N. Khawaja , T.F. Renton , F.O. Zelaya , M.A. Thacker , S.C.
1
1
Williams , M.A. Howard
1
2
Department of Neuroimaging, MRC Social, Genetic and Developmental Psychiatry Centre, King's
3
College London, Institute of Psychiatry, King's College London, Dental Institute, London, UK
Background and aims: Neuroimaging research has begun to unravel the cerebral response to pain
using arterial spin labelling (ASL) perfusion Magnetic Resonance Imaging (MRI) techniques. Here we
evaluate the test-retest performance of concurrent pulsed-continuous ASL (pCASL) and visual
analogue scale (VAS) indices of clinical on-going pain following third molar extraction (TME).
Methods: 16 male subjects requiring bilateral lower-jaw TME attended four scanning sessions: two
pre-surgery sessions (S1 & S3), and two post-surgery sessions following first (S2) and second tooth
extraction (S4). MRI was performed at 3T using pCASL. Subjects also provided in-scanner ratings of
pain using VAS. Regional cerebral blood flow (rCBF) changes were calculated using a two-way
ANOVA of the combined session-pairs (Pair 1[S1,S2]/Pair 2[S3,S4]). Reliability of VAS reports and
rCBF values in brain regions (ROIs) acknowledged to underpin the pain experience, were quantified
at both group and individual case levels using intra-class correlation coefficient (ICC).
[Figure 1]
Results:
[VAS] Pain ratings were significantly higher in post-surgical sessions (Figure1). Interestingly, only
within-subject VAS scores were reliable (ICC Between-subject=0.457; Within-subject=0.602).
[pCASL] Significant post-surgical rCBF increases were identified in all ROIs (Figure2A). Within-and
between-subjects, regional ICC values were highly reliable across post-surgical pain states (see
Figure 2B).
[Figure 2]
Conclusions: Used together, VAS and pCASL-derived rCBF pain-indices provided reliable measures
of within- and between-subject baseline differences in pain response. rCBF measures offer the
enticing potential to add value to conclusions derived from traditional patient self-reports.
Between-subject reliability
Within-subject reliability
Visual Analogue
Scales
ICC
CV
ICC
CV
Pain
0.457
0.285
0.602
0.200
Alertness
0.664
0.359
0.640
0.203
[Table 1]
790
A NOVEL APPROACH TO PREDICT SUBJECTIVE PAIN PERCEPTION FROM SINGLE-TRIAL
LASER-EVOKED POTENTIALS
1
2
2
1
P. Xiao , G. Huang , Z. Zhang , L. Hu , G. Iannetti
3
1
Key Laboratory of Cognition and Personality (Ministry of Education), School of Psychology,
2
Southwest University, Chongqing, Department of Electrical and Electronic Engineering, The
3
University of Hong Kong, Hong Kong, China, Department of Neuroscience, Physiology and
Pharmacology, University College London, London, UK
Background and aims: Pain is a subjective first-person experience, and self-report is the gold
standard for pain assessment in clinical practice. However, self-report of pain is not available in some
vulnerable populations (e.g., patients with disorders of consciousness), which leads to an inadequate
or suboptimal treatment of pain. Therefore, the availability of a physiology-based and objective
assessment of pain that complements the self-report would be of great importance in various
applications. Here, we aimed to develop a novel and practice-oriented approach to predict pain
perception from single-trial laser-evoked potentials (LEPs).
Methods: We applied a novel single-trial analysis approach that combined common spatial pattern
and multiple linear regression to automatically and reliably estimate single-trial LEP features. Further,
we adopted a Naïve Bayes classifier to discretely predict low and high pain and a multiple linear
prediction model to continuously predict the intensity of pain perception from single-trial LEP features,
at both within- and cross-individual levels.
Results: Our results showed that the proposed approach provided a binary prediction of pain
(classification of low pain and high pain) with an accuracy of 86.3±8.4 % (within-individual) and
80.3±8.5 % (cross-individual), and a continuous prediction of pain (regression on a continuous scale
from 0 to 10) with a mean absolute error of 1.031 ± 0.136 (within-individual) and 1.821 ± 0.202 (crossindividual).
Conclusions: The proposed approach may help establish a fast and reliable tool for automated
prediction of pain, which could be potentially adopted in various basic and clinical applications.
791
INTRINSIC CONNECTIVITY NETWORKS IN CHRONIC PAIN
A. Khusnullina, N. Goulden, J. Jones, P. Mullins
School of Psychology, Bangor University, Bangor, UK
Background and aims: Chronic pain has been associated with changes in brain activity. This study
aimed to explore these changes within widespread (fibromyalgia-FM) and local pain (knee
osteoarthritis-OA) as reflected by activity within and between three regions of interest (ROI): the
default mode network (DMN) and the executive attention networks left and right (EANL and EANR) in comparison to each other and to healthy controls (HC).
Methods: Resting-state fMRI data from 9 FM patients, 14 OA patients and 12 HC were acquired.
Seed regions were placed in the posterior cingulate cortex and superior temporal gyrus: extracted
signals were correlated with brain activity within all ROI. Then results were narrowed down by
applying masks representing DMN, EANL and EANR.
Results: Functional connectivity (FC) was elevated in FM compared to HC within all ROI and in
comparison with OA in ROI1 when applied DMN mask. Moreover, FC was increased in OA compared
to HC in ROI1 and ROI2 by applying DMN mask. In contrast, resting state FC was decreased in OA in
comparison with HC within ROI2 and ROI3 when applied EANL mask. In FM it was reduced in ROI2
by applying EANL and EANR masks.
Conclusions: This study demonstrates differences in resting state FC of chronic pain conditions.
Investigation of further chronic pain conditions using fMRI would enable the elucidation of the
mechanisms underlying pain. The finding of increased FC in DMN and suppressed FC in EAN in
chronic pain may assist the development of new target therapies.
792
STRUCTURAL BRAIN CORRELATES OF PAIN CATASTROPHISING IN HEALTHY PEOPLE
X. Li, N. Fallon, H. Wright, A. Stancak
Department of Experimental Psychology, University of Liverpool, Liverpool, UK
Pain catastrophising, an exaggerated negative orientation towards actual and anticipated pain, is
increasingly considered to be an important factor in the experience of pain. The purpose of this study
was to analyse associations between the structure of the cortical grey matter and pain
catastrophising.
T1-weighted, high-resolution anatomical images of the head have been acquired in 46 healthy
participants (33 females, age range 18-55 years) using a 3-Tesla Siemens Trio MR scanner. A VoxelBased Morphometry (VBM) involving Diffeomorphic Anatomical Registration Through Exponentiated
Lie Algebra (DARTEL) was employed to evaluate grey matter volumes. A Gaussian kernel sized 10mm at full width at half maximum was employed to smooth anatomical images. Multivariate regression
analysis was computed in SPM8 using the scores of Pain Catastrophising Scale, State and Trait
Anxiety Inventory, Fear Of Pain, age and gender as independent variables. An uncorrected threshold
of P < 0.001 and a cluster size of 50 contiguous voxels were employed.
Multiple regression analysis showed a positive correlation between pain catastrophising scores and
regional grey matter volume of left superior frontal gyrus, right temporal medial gyrus, right
parahippocampal gyrus, anterior mid-cingulate cortex (BA31), and right paracentral lobule (BA5/7),
controlling for age, gender, anxiety and fear of pain.
Results suggest that increased volume in regions participating in emotional processing
(parahippocampal gyrus), pain (anterior mid-cingulate cortex) and frontal and temporal association
cortices may predispose to a heighted level of pain catastrophising.
793
DECODING THE PAINFUL QUALITY OF SENSORY PERCEPTS FROM HUMAN BRAIN ACTIVITY
1
2
M. Liang , A. Mouraux , G.D. Iannetti
1
1
Department of Neuroscience, Physiology and Pharmacology, University College London, London,
2
UK, Institute of Neuroscience (IoNS), Université Catholique de Louvain, Brussels, Belgium
Background and aims: The identification of neural activity specifically underlying the emergence of
painful sensations has both fundamental implications in sensory neuroscience and clinical relevance.
In this study we aimed to identify patterns of cortical activity specific for the painful quality of the
elicited sensations in humans.
Methods: Multivariate pattern analysis (MVPA) identifies the representational content of the fMRI
responses elicited by, e.g., different stimuli. MVPA is more sensitive than univariate analysis in
disclosing differences in brain activities between experimental conditions, and allows obtaining novel
physiological information (e.g. Liang et al Nat Commun 2013). Here we applied within-subject
searchlight MVPA to fMRI responses to iso-salient stimuli of four sensory modalities (pain, touch,
audition and vision), in 14 healthy participants. Quality discriminations (“pain vs. touch”, “pain vs.
audition” and “pain vs. vision”) resulted in three accuracy brain maps which were further statistically
thresholded at group level (against chance level; P< 0.01, FDR corrected). A conjunction map was
finally obtained with the voxels surviving in all three maps, to identify areas encoding painful percepts.
Results: Several brain areas contained unique pain signatures. Notably, these were also present in
areas outside the so-called “pain matrix”, and included primary and higher-order association areas.
Conclusions: The painful quality of sensory experience is widely encoded in many brain areas,
beyond the so-called “pain matrix”. This finding represents a necessary step towards understanding
the mechanism of pain perception and identifies a biomarker for painful percepts.
794
FUNCTIONAL TRACING BY FREQUENCY CODING REVEALS CONVERGENCE IN HUMAN
PAINFUL AND PLEASANT TOUCH PATHWAYS
L. Löken, E. Duff, I. Tracey
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
Background and aims: We here investigated the central processing of firing rates in Aβ and CLTMs
on normal and sensitized skin during ongoing pain, in order to determine how their respective firing
rates influences C fibre activity to produce affective experiences spanning pain, pleasure and
analgesia.
Methods: Using a within subjects design, we compared perception and central neural processing of
soft brush stroking at varying velocity on normal and capsaicin sensitized skin in 19 healthy
individuals while recording behaviour and functional magnetic resonance imaging (fMRI), respectively.
The protocol was designed to modulate known firing rates in CLTM and Aβ afferents.
Results: Within the area of sensitization, Aβ afferent discharge rates interact with C fibre
hyperexcitability in a linear fashion such that the percept shifts from allodynia to analgesia. Outside
the sensitized area, all brushing was assessed as pleasant but most efficient when producing high
discharge rates in CLTM afferents. Modeling the unique firing rate signatures of Aβ and CLTMs to
fMRI data showed that the central processing of activity related to these two fibre classes were
modulated in different ways depending on whether brushing was on the area of sensitization or on
normal skin.
Conclusion: We show that brush evoked allodynia and analgesia in sensitized skin depends on Aβ
fibre discharge rate and that patterns of activity from specific afferents interact centrally to produce
affective sensations. Previously designated discriminative, nociceptive and hedonic circuits are not
separate static channels but shared across modalities, integrated and modulated to produce affective
percept.
795
AXON REFLEX-MEDIATED VASCULAR RESPONSE IN PERSONS WITH MIGRAINE
1
1
2
3
1
4
A. Plinta , I. Logina , P. Tretjakovs , R. Erts , L. Meksa , I. Kalere , G. Bahs
1
5
2
Department of Neurology and Neurosurgery, Department of Human Physiology and Biochemistry,
4
5
Department of Physics, Riga Stradins University, Health Centre - 4, Department of Family
Medicine, Riga Stradins University, Riga, Latvia
3
Aims: The aims of the present study was evaluation of main parameter of micro-vascular reactivityaxon reflex-mediated or 1st maximum, in response to heating during interictal period in persons,
suffering from migraine and healthy volunteers, and compare the results.
Methods: 43 women suffering from migraine (group M; 41+/- 9,7 y.o.) and 46 age and body mass
index (BMI) matched healthy volunteers (group C; 34+/-7,1 y.o.) underwent laser Doppler imaging
(laserDopplerMoor, LDI) to measure cutaneous microvascular blood flow on the dorsal side of palm
0
as a response to the local heating (+44,0 C). BMI in group M: 23,4+/-3,4; group C: 24,2+/-4,9. Time
(min) to reach the first peak perfusion and perfusion peak (perfusion units, PU) was measured.
Results: The axon reflex-mediated peak maximum statistically significantly earlier was achieved in M
group (6.33 + / -1.29 min., C group 8.26 + / -2.56 min.), p< 0.001. Although the increase of perfusion
peak value from baseline in migraineurs and healthy persons did not differ significantly (p> 0.05),
however statistically significant variance dispersion over a wide range in M group (Leuven test, p <
0,05) was found. Age, BMI, hormonal contraceptives, smoking, and a scan season (winter or
summer), had no statistically significant impact on axon reflex-mediated cutaneous microvascular
blood flow maximum (p> 0.05).
Conclusions: The data show significant differences in microvascular vasodilatation reaction in
migraine compared to the control group even during interictal period. Maximum neuropeptide-induced
vasodilatation is reached markedly earlier in migraine sufferers.
796
LEPS ARE DEPENDENT ON THE DISTANCE BETWEEN THE STIMULATED HAND AND THE
FACE
1,2
1
3
I. Ronga , C. Sambo , A. Mouraux , G.D. Iannetti
1
1
Department of Neuroscience, Physiology and Pharmacology, University College London, London,
2
UK, Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (NICO), University of Turin, Turin,
3
Italy, Institute of Neuroscience (IoNS), Universite Catholique de Louvain, Brussel, Belgium
Background and aim: Laser-evoked potentials (LEPs) are dependent on the spatial position of the
stimulated hand within the body-centred frame of reference (Gallace et al. Pain 2011). Furthermore,
the eye blink elicited by hand stimulation is enhanced when the stimulated hand is located close to
the face, thus defining a defensive peripersonal space (DPPS; Sambo et al. J Neurosci 2012). Here
we tested whether LEPs are also enhanced when the hand is closer to the face.
Methods: LEPs elicited by single laser pulses delivered to the right hand dorsum were recorded in 17
healthy volunteers. Participants were seated with the hand in three different positions:
(1) resting on a table, at ~60 cm from the body midline, on the right side;
(2) ~4 cm from the stomach;
(3) ~4 cm from the ipsilateral side of the face.
Results: We observed a trend of a modulation of the amplitude of the N2 LEP as a function of the
distance between the hand and the face - with larger amplitudes of the N2 peak when the hand was
closer to the face (p=0.04, test for linear trend at Cz).
Conclusion: Given that LEPs are largely related to the detection and reaction to potentially
dangerous sensory events (Ronga et al. J Neurophysiol 2013), this result suggests that (1) stimuli
delivered in the space surrounding the body induce more efficient self-protective actions, and (2) the
space surrounding the face represents a “highest-risk area” that needs to be protected more
effectively.
797
NEUROPHYSIOLOGICAL CORRELATES OF TONIC PAIN
E. Schulz, L. Tiemann, M. Postorino, M. Ploner, PainLabMunich
Department of Neurology, Technische Universität München, München, Germany
Recent functional imaging and neurophysiological studies have significantly extended our knowledge
about the cerebral processing of pain. However, most of these results originate from experimental
studies using brief painful stimuli. Whether and how these findings translate to the main clinical
problem of tonic and chronic pain is largely unknown yet.
Here, we used EEG to explore neuronal activity that code for the intensity of long-lasting tonic pain.
During the recording of a 64 channel EEG, we applied tonic heat pain and phasic laser pain in two
counterbalanced experiments to healthy human subjects. The intensity of the stimuli was adapted to
the subjects' individual pain level (analogue scale: 30 to 70, max. 100). Our results confirm recent
findings showing that the intensity of phasic pain is related to neuronal theta, alpha and gamma
activity. Moreover, our results reveal that neuronal activity at theta, beta and gamma frequencies code
for the intensity of long-lasting tonic pain. Interestingly, these topographies differ from those of phasic
pain.
Taken together, the present investigation shows an ecologically more valid representation of the
perception of pain in the human brain. It supports other evidence that a number of neuronal
processes, brain regions and brain responses (such as gamma and theta activity) contribute to the
highly subjective experience of pain.
798
BRAIN MORPHOMETRY IN CHRONIC LOW BACK PAIN
1,2
1
1
N. Spahr , D. Hodkinson , S. Williams , M. Thacker
1,2,3
, M. Howard
1
1
Pain Research Group, Department of Neuroimaging, Institute of Psychiatry, King's College London,
3
Physiotherapy Department, Guy's and St Thomas' NHS Foundation Trust, Centre of Human and
Aerospace Physiological Sciences, King's College London, London, UK
2
Background and aims: There is growing evidence that chronic low back pain (LBP) is associated
with grey matter brain abnormalities. Here we investigated the effect of chronic LBP on patients' grey
matter (GM) volumes using voxel-based morphometry (VBM).
Methods: 49 patients with CLBP [26 with mechanical low back pain (MLBP) and 23 subjects with
neuropathic LBP (NuLBP)] were compared to 19 age and sex-matched healthy controls. 3D T1weighted MRI data were acquired using an SPGR sequence available on a GE 3T scanner. VBM
preprocessing (normalisation and segmentation using DARTEL and smoothing with a 8mm isotropic
Gaussian kernel) and analyses were performed using the VBM8 toolbox available in SPM8.
Groupwise differences in absolute GM volume were assessed using ANCOVA. Daily pain scores,
age, gender and intra-cranial volume were included as co-variates. Results images were thresholded
at alpha-p< 0.05 following non-stationarity cluster-extent correction.
Results: Compared to controls, patients with CLBP demonstrated significant reduction in GM volume
in bilateral superior frontal gyri and left hemisphere postcentral gyrus. In patients with NuLBP,
compared to MLBP, significant relative GM reductions were identified in medial orbital-frontal cortex
bilaterally and left hemisphere precentral gyrus; relative GM increases were found in brainstem and
precuneus (Figure 1).
[Fig 1: Grey matter alterations among groups]
Conclusions: We have demonstrated significant GM volume alterations in patients with CLBP that
differ due to underlying clinical phenotypes. These novel findings add weight to the burgeoning
evidence-base of disease-state specific 'neurosignatures' in patients with persistent pain states.
799
COMBINED FMRI OF THE HUMAN BRAIN AND THE CERVICAL SPINAL CORD TO STUDY THE
CNS PROCESSING OF PAIN
C. Sprenger, J. Finsterbusch, C. Buechel
Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg,
Germany
Background: Numerous studies used BOLD-sensitive whole-brain fMRI to investigate the central
representation of pain. More recently also fMRI of the human spinal cord became feasible. However, it
is desirable to acquire activity in both regions within one single measurement to study the functional
interplay between the brain and the spinal cord.
Methods: Measurements were performed on a Siemens Trio 3T system using a 12-channel head and
4-channel neck coil. Two subvolumes, consisting of 32 slices covering the brain and 8 slices centred
at the spinal segment C6. Acquisition parameters were individually adapted to the favored setting for
each region. Importantly, a dynamic update of resonance frequency and linear shims was
implemented in order to provide an optimized shim adjustment for both regions. 17 healthy volunteers
completed a pain experiment consisting of 3 sessions. During each session 8 low and 8 high intensity
thermal stimuli were applied to the left forearm (dermatome C6).
Results: In the brain, we observed a typical pattern of pain-related BOLD responses to both thermal
intensities. At the spinal level we observed strongest BOLD responses to high thermal intensity
ipsilateral to the side of stimulation in the dorsal horn of the spinal segment C6. A significant higher
activation to high thermal intensity compared to low intensity was present at the same spinal level. A
psychophysical interaction analysis demonstrated the functional coupling between the spinal cord and
pain responsive brain regions.
Conclusion: Combined spinal and supraspinal fMRI is feasible and opens up new perspectives for
pain research.
800
NEURONAL CODING OF BOTTOM-UP AND TOP-DOWN MODULATIONS OF PAIN PERCEPTION
L. Tiemann, E. Schulz, M. Ploner
Technische Universität München, Munich, Germany
Background and aims: The perception of pain does not linearly reflect nociceptive input, but
essentially depends on contextual parameters. In the brain, painful stimuli yield different neuronal
responses, which provide complementary information about pain perception. Whereas neuronal theta
oscillations (3-8 Hz) reflect stimulus-driven bottom-up determinants of pain, previous studies suggest
that neuronal gamma oscillations (30-100 Hz) may relate to top-down mediated modulations of pain
perception.
Methods: We recorded electroencephalography (EEG) and applied painful laser stimuli while healthy
subjects participated in two paradigms. In the first paradigm, variations of pain were induced by
variable objective stimulus intensities (bottom-up). In the second paradigm, we applied placebo
analgesia to induce variations of pain due to different expectations (top-down). Theta and gamma
oscillations were related to changes in subjective pain perception by means of logistic regression.
Results: First results suggest that changes in theta oscillations particularly reflect modulations of
objective sensory input. On the other hand, changes in gamma oscillations appear to particularly
reflect those changes in subjective pain perception, which are solely based on expectations.
Conclusions: Our study directly compares bottom-up and top-down mediated modulations of pain.
First results suggest that different modulations of pain are differentially related to neuronal responses
at different frequencies, indicating that they represent different steps in the integration of external
sensory information and top-down mediated contextual information into a subjective percept.
801
FUNCTIONAL MICROSTATE ANALYSIS AS A MEANS TO ASSESS THE EFFECT OF STIMULUS
REPETITION ON NOCICEPTIVE-EVOKED POTENTIALS
1,2
3
3
E. Valentini , C. Zhao , L. Hu
1
2
3
Psychology, Sapienza University of Rome, Santa Lucia Foundation, Rome, Italy, School of
Psychology, Southwest University, Chongqing, China
Background and aims: The processes of deviance detection and sensory memory trace formation in
nociceptive and somatosensory systems are largely unknown if compared to the auditory system. A
novel analytical approach based on functional microstates (i.e., scalp topographies with quasi-stable
landscape) was devised to identify the effect of stimulus repetition on nociceptive-evoked potentials
(NEPs) and somatosensory-evoked potentials (SEPs), compared to auditory-evoked potentials
(AEPs).
Methods: NEPs, SEPs and AEPs were recorded using electroencephalography in 30 volunteers.
Trains of intraepidermal, transcutaneous, and auditory stimuli were delivered either while participants
were attending to (active), or distracted from (passive), the stimulation. Stimuli were administered
according to a roving paradigm: the first stimulus in each train is a deviant that become a standard
through repetition. A topographical segmentation analysis was performed on the ´repetition´
modulated and signed F-value time courses of NEPs, SEPs and AEPs, to identify their respective
functional microstates.
Results: The ´repetition´ modulated microstate in NEPs, detected at 155-273 ms, showed a negativity
at bilateral temporal regions. The ´repetition´ modulated microstates in SEPs, detected at 64-160 ms
and 161-245 ms, showed a negativity at bilateral temporal regions. The ´repetition´ modulated
microstate in AEPs, detected at 92-193 ms, showed a negativity at bilateral frontal region. Generally,
st
nd
ERP amplitudes suppressed largely from the 1 stimulus to the 2 stimulus, and varied minimally
th
after the 4 stimulus in a train.
Conclusions: The effects of stimulus repetition are spatially distinct but temporally similar for NEPs
and SEPs as compared to AEPs.
802
CENTRAL INTEGRATION OF BILATERAL ACUTE PAIN
N. Vartiainen
1,2,3
1,2
4
, Y. Hlushchuk , E. Kalso , N. Forss
1,5,6
1,2
, R. Hari
1
Brain Research Unit, O.V. Lounasmaa Laboratory, Aalto Neuroimaging, School of Science, Aalto
2
University, Magnetic Imaging Centre, Aalto Neuroimaging, School of Science, Aalto University,
3
Espoo, Finland, Central Integration of Pain (NeuroPain), Lyon Neuroscience Research Center
4
(INSERM U 1028 / CNRS UMR 5292 / Univ. Lyon 1), Lyon, France, Department of Anaesthesia and
5
Intensive Care Medicine, Pain Clinic, Helsinki University Central Hospital, Department of Neurology,
6
Helsinki University Central Hospital, Department of Neurological Sciences, University of Helsinki,
Helsinki, Finland
Background and aims: Sensory stimuli to the two body halves are integrated in the CNS. To
auditory and somatosensory stimuli, the cortical responses to bilateral stimuli are smaller than the
sum of responses to unilateral stimuli presented in isolation, suggesting bilateral suppressive
integration. We aimed to characterize the so-far unknown bilateral integration of acute pain in the
human brain.
Methods: We measured blood-oxygen-level-dependent responses from eleven healthy subjects,
receiving painful heat stimuli to the left and right hands, or at the same time to both hands. Regions of
interests were defined on the basis of pain-related activations in a prior experiment.
Results: We found three differently behaving groups of brain areas. In the anterior and middle insular
cortex, the secondary somatosensory cortex/posterior insula, and the striatum bilaterally, and in the
anterior cingulate cortex, the pain-related activations to bilateral stimuli were equal in amplitude to the
sum of unilateral responses (linear additivity). In the posterior parietal cortex and premotor cortex, the
activations to bilateral stimuli were stronger than the sum of responses to unilateral stimuli (supraadditivity). In the primary sensorimotor cortices, the medial prefrontal cortex and the precuneus, the
deactivations were equally strong to bilateral and unilateral stimuli (suppressive integration).
Conclusion: The brain regions showing linear additivity suggest independent processing of
nociceptive input from both sides of the body. The regions showing supra-additive behaviour likely are
involved in sensorimotor planning for coordination in pain-eliciting environment. The areas showing
deactivations appear to be maximally recruited already by unilateral pain.
803
NEURAL CORRELATES OF PAIN RELIEF EXPECTATION IN A DOUBLE BLIND PLACEBO
CONTROLLED STUDY SETTING
V. Wanigasekera, M. Mezue, Y. Kong, I. Tracey
University of Oxford, Oxford, UK
Background: Expectation of pain relief is central to placebo analgesia. Increased functional
connectivity (FC) between perigenual cingulate (pgCC) and nuclei such as the amygdalae and
periaqueductal grey (PAG) has been shown in placebo-induced analgesia. We studied how subtle
expectancy, induced in a double blind placebo controlled study (DBPCs) modulates such connectivity.
Methods: In healthy subjects, FC of amygdalae was compared between a no treatment arm and
placebo arm of a DBPCs investigating analgesic efficacy. Using a visual analogue scale, subjects
rated expectation of pain relief (EPR) 90mins after study medication but before inducing pain with
topical capsaicin. Resting state functional scans were acquired after 1.5hours of capsaicin. Subjects
returned on a separate day on completion of the DBPCs. Study procedures were repeated with no
expectation of pain relief.
Results: A significantly higher placebo induced FC between amygdalae and pgCC was found in
subjects with higher EPR scores despite an overall small EPR magnitude [mean (±SD) 18.87
(±16.97)] insufficient to induce placebo analgesia. No such effect was found between amygdalae and
PAG.
Conclusions: Dorsolateral prefrontal cortex (dlPFC) is key to maintaining expectancies. pgCC
projects directly to amygdalae and dlPFC. Direct projections between amygdalae and dlPFC are
sparse. The subtle EPR effects in a DBPCs without analgesic effects allowed isolation of effects
specific to EPR. Our data suggest pgCC links dlPFC with amygdalae to mediate expectancy-induced
effects, but increased FC between amygdalae and PAG during expectancy is needed for placebo to
induced analgesia.
Acknowledgements: Innovative Medicines Initiative project EUROPAIN
804
STRUCTURE, FUNCTION AND EXPERIENCE: A MULTIMODAL INVESTIGATION OF THE
LATERAL PAIN SYSTEM
T. Warbrick, V. Fegers-Stollenwerk, I. Maximov, F. Grinberg, N.J. Shah
Institute of Neuroscience and Medicine, Forschungszentrum Juelich, Juelich, Germany
Background and aims: Changes in DTI metrics such as fractional anisotropy (FA) are associated
with pain disorders such as fibromyalgia, trigeminal neuralgia and irritable bowel syndrome. However,
the relationship between measures of microstructure integrity, functional brain responses and the
subjective experience of pain are poorly understood. We investigate the relationships between these
measures in healthy control subjects to illustrate how multimodal investigations can advance our
knowledge of the pain system.
Methods: BOLD fMRI was measured from 16 healthy male subjects during painful thermal stimulation
of the right arm. Ratings of perceived stimulus intensity were obtained after each block. Diffusionweighted images were acquired for each subject and all subjects' data were coregistered to MNI
space before extracting FA estimates from SI, thalamus and putamen. Pain ratings and mean FA
values were included as regressors in the fMRI analysis to investigate the relationships between
these measures and fMRI BOLD response.
Results: Pain intensity ratings were positively related to BOLD activation in the putamen and
thalamus but not S1. FA was negatively related to BOLD activation in the thalamus, putamen and S1.
FA was not related to subjective pain ratings.
Conclusions: Pain intensity ratings were related to BOLD activation in the lateral pain system.
Increased FA in these regions was related to reduced BOLD signal suggesting that microstructure
integrity in these regions is related to the functional brain response to pain. These data show that
multimodal imaging can contribute to the further investigation of pain disorders.
805
ISOBOLOGRAPHIC ANALYSIS OF THE ANTINOCICEPTIVE INTERACTION BETWEEN SODIUM
VALPROATE AND TRAMADOL
1
1
2
V. Bild , C.L. Chitac , W. Bild
1
2
Pharmacodynamics and Clinical Pharmacy, Physiology, University of Medicine and Pharmacy 'Gr T
Popa' Iasi, Iasi, Romania
Background and aim: This work is part of a larger approach concerning the interactions between
anticonvulsants and drugs with analgesic action.
Method: the study used Swiss male mice wighing 20-25 grams, separated in groups of 6-10 animals.
As nociception model was used the abdominal constrictive response, induced with zymosan. The
data were interpreted in a quantal manner, characterized by the presence or absence of responses.
The substances were administered orallly, alone or in combinations. For the study of fixed-ratio
combination we used the isobolar analysis. the experimental protocols were in agreement with the
national and international bioethical regulations.
Results: Experimental data demonstrated a synergism between sodium valproate and tramadol
(Zmix=4.39±1.06, Zadd=16.00±3.08, gamma=0.275, tc=4.18, tt=3.57, FC=12.78, Ft=4.46, p< 0.05).
Conclusions: the results encourage the use of combinations between anticonvulsants and opiate
analgesics on pain conditions. The advantage resides in the reduction of the doses for both drugs
(synergistic effect), which will reduce the risk of side-effects and it might lead to a multi-modal
covering of a wider spectrum of pain types.
806
DEVELOPMENT AND CHARACTERISATION OF A NOVEL, ANATOMICALLY RELEVANT RAT
MODEL OF ACUTE POSTOPERATIVE PAIN
1
1
1
1
1
2
3
1
D. Bree , O. Moriarty , C. O'Mahony , B. Morris , K. Bannerton , D. Broom , M. Roche , D. Finn , J.
1
Kelly
1
2
Pharmacology and Therapeutics, NUI Galway, Galway, Ireland, Research and Development,
3
Covidien, New Haven, CT, USA, Physiology, NUI Galway, Galway, Ireland
Background/aims: Acute postoperative pain remains a significant healthcare issue. Development of
anatomically relevant models of postoperative pain, with improved predictive validity, would advance
understanding of postoperative pain mechanisms and improve treatment outcomes. We aimed to
develop, characterise and validate a rat model of acute postoperative pain associated with inguinal
hernia repair.
Methods: Under isoflurane anaesthesia (5% induction, 2.5% maintenance), adult male Lister-Hooded
rats underwent surgery to model Lichtenstein inguinal hernia repair, or a sham procedure (n=6-12 per
group per experiment). Post-surgical characterisation involved extensive monitoring of home cage
and open field locomotor activity. Rats received morphine (7mg/kg, 10mg/kg), carprofen (5mg/kg,
10mg/kg), paracetamol (75mg/kg, 150mg/kg) or vehicle s.c. 1hr before and/or immediately after
surgery. Animals were transcardially perfused and spinal cord sections stained for c-Fos. Data were
analysed by repeated-measures or one-way ANOVA or by t-tests as appropriate.
Results: Rats that underwent hernia repair surgery exhibited significantly (p< 0.05) lower horizontal
and vertical activity than sham rats in the home cage and open field in the early post-surgical period.
Carprofen and paracetamol significantly attenuated the surgery-induced decreases in locomotor
activity, without affecting activity of sham animals. Morphine significantly increased activity in both
sham and surgery rats compared to vehicle-treated controls. Surgery was associated with significantly
increased c-Fos expression in the ipislateral dorsal horn of the spinal cord.
Conclusions: These results support the development and characterisation of a novel, anatomically
relevant model of acute postoperative pain, which may facilitate development of improved treatments
for postoperative pain.
Supported by the IDA and Covidien.
807
ROLE OF SEROTONERGIC AND ENDOCANNABINOID SYSTEMS ON THE ANTINOCICEPTION
INDUCED BY ORAL ACUTE ADMINISTRATION OF SWEET SUBSTANCE IN ADULT RODENTS
F.A. Oliveira, R.L. Freitas, N.C. Coimbra, M.A. Rédua
Department of Pharmacology, Ribeirão Preto Medical School - University of São Paulo, Ribeirão
Preto, Brazil
Background and aims: There is evidence that sweetened substances cause antinociception in
young and adults rats. Considering the lack of pharmacological explanations of this phenomenon, the
aim of the present work was to investigate the role of 5-HT1A and CB1 receptors, as well as the
interaction between endocannabinoid and serotonergic systems in the antinociception induced by
acute intake of sucrose in an animal model of pain.
Methods: Male Wistar rats (n=6-8 per group) were submitted to the tail-flick test baseline recording
and pre-treated by intraperitoneal (IP) administrations of the non-selective serotonergic receptors
antagonist methysergide, the 5-HT1A serotonergic receptors antagonist WAY100635, the
endocannabinoid agonist cannabidiol, the CB1 receptors antagonist AM251, at different doses (0.25,
1.0 and 4.0mg/kg), or vehicle. It was also performed the pre-treatment with IP-administration of
AM251, methysergide, WAY100635, followed by IP-administration of cannabidiol (at the higher dose,
in all cases), or vehicle. After, each animal was submitted to an oral treatment with 25% sucrose or
tap water and the nociceptive threshold was measured for 30 minutes.
Results: The sweet substance-induced antinociception was decreased by the pre-treatment with
methysergide, WAY100635 and AM251 (P< 0.05, in all cases). The cannabidiol increased the
antinociception induced by oral administration of 25% sucrose; effect antagonized by IPadministration of AM251, methysergide or WAY 100635 (P< 0.05, in all cases).
Discussion: These findings suggest the recruitment of 5-HT1A and CB1 receptors in the organization
of sucrose-induced antinociception. Moreover, cannabidiol potentiated the sweet substance-induced
antinociception through the activation of CB1 and 5-HT1A receptors in adult rodents.
808
TLR4-A1, A TOLL-LIKE RECEPTOR 4 ANTAGONIST, REDUCES OPIOID HYPERALGESIA IN A
RAT MODEL OF POSTOPERATIVE PAIN
1
1
2
1
M.Á. Martínez-García , D. Pascual , E. Quesada , M.I. Martín-Fontelles , C. Goicoechea
1
1
2
Pharmacology, Universidad Rey Juan Carlos, Alcorcón, Instituto de Química Médica, CSIC, Madrid,
Spain
Background: Postoperative pain is a common form of acute pain. Treatment with opioids can induce
hyperalgesia in humans and animals, and activation of Toll-like receptor 4 (TLR4) has been proposed
to induce such hyperalgesia.
Aim: To assess whether TLR4 receptors blockade can prevent the development of morphine-induced
hyperalgesia and alodynia in a rat model of postoperative pain.
Methods: Adult (250-300g) male Wistar rats were used. After baseline measurements of nociceptive
threshold, the rat model of incisional pain (Brennan et al. 1996) was performed. Heat-hyperalgesia
and tactile-allodynia were tested to evaluate after the following treatments (all drugs were i.p.
administered): saline, morphine (5mg/kg/twice-a-day), TLR4-A1 (5mg/Kg/twice-a-day) and TLR4-A1 +
morphine). Tests were carried out daily, immediately before drugs administration.
Results: Incision of the plantar surface of the hind paw produced a statistically-significant
mechanical-allodynia (decrease of mechanical threshold on 58.31% vs 100% control) and heat
hyperalgesia (decrease of thermal threshold on 42.4% vs 100% control). Morphine treatment did not
reduce tactile-allodynia nor heat-hyperalgesia during the 9 days following. TLR4-A1 treatment
reduced tactile-allodynia and heat-hyperalgesia; values returned to control threshold, (on day 5 for
allodynia and on day 2 for hyperalgesia). Co-administration of TLR4-A1 and morphine accelerates the
recovery to the control threshold, compared with morphine-treated animals.
Conclusion: This study suggests that blocking TLR4 receptor may be a stand-alone or coadyuvant
therapeutic option for treating postoperative pain.
Ackowledgements: Maria del Carmen Merino for technical support.
809
NOCICEPTIVE BEHAVIOURAL THRESHOLDS FOR CUTANEOUS MECHANICAL AND HEAT
STIMULATION OF THE TAIL ROOT IN PIGS
1
2
3
3
P. Di Giminiani , D. Sandercock , R. Rukwied , M. Schmelz , M.S. Herskin
1
1
2
Dept Anim Sci, Aarhus University, Tjele, Denmark, Animal and Vet Science Research Group,
3
SRUC, Edinburgh, UK, Dept Anesthesiology and Intensive Care Medicine, Heidelberg University,
Mannheim, Germany
Background and aims: The use of pigs in translational pain research is increasing. However, only
few methods are available to behaviourally quantify porcine nociceptive thresholds. Our aim was to
determine baseline mechanical and thermal nociceptive thresholds using behavioural assays in pig
with the tail root as stimulation site.
Methods: Eight female pigs were used (50±5 kg, 15 weeks of age) and habituated to procedures
before testing. Two mechanical (von Frey filaments (vF), pressure application measurement device
(PAM)) and one thermal assay (CO2 laser) were used. Behavioural responses to stimulation at a 2 x 2
cm test area on the dorsal tail base were measured during one test session while the pigs were kept
in a test cage and accompanied by a pen mate for social support. Within the test session each assay
involved three stimulations per pig.
Results: All assays provided robust values for nociceptive thresholds, with a mean of 5±1 sec (CO 2);
422±35 gf (PAM) and 73±11 gf (vF). The responses to the 24 single stimulations ranged from 1-17
sec, 212-890 gf and 26-300 gf for CO2, PAM and vF. The observed behavioural responses were tail
flicks (88, 8 and 29 %), tail clamps (0, 0 and 63 %), rump flinches (4, 83 and 0 %) and body
movements (8, 8 and 8 %) respectively.
Conclusions: Using these experimental approaches and behavioural assays already described for
rodents, it was possible to quantify mechanical and thermal nociceptive thresholds on the tail roots of
standing pigs.
810
THE EFFECT INTRADERMAL NGF INJECTION ON TEMPORAL CHANGES IN CUTANEOUS
MECHANICAL AND THERMAL SENSITIVITY IN PIGS
1
2
2
3
3
D. Sandercock , P. Di Giminiani , M. Herskin , R. Rukwied , M. Schmelz
1
2
Animal and Veterinary Science Research Group, SRUC, Edinburgh, UK, Department of Animal
3
Science, Aarhus University, Foulum, Denmark, Department of Anaesthesiology and Intensive Care
Medicine, Heidelberg University, Mannheim, Germany
Background and aims: We investigated effects of intradermal NGF injection on cutaneous
mechanical and thermal sensitivity in pigs.
Methods: Eight female pigs (50±5kg; 15 weeks of age) were habituated to the procedures before
testing. Treatment pigs (n=4) received either 10µg NGF (in PBS; 0.1% BSA) or PBS vehicle (control)
in 25 x 20µl intradermal injections into a 5x5cm area tail root. Two mechanical (von Frey filaments
(vF), pressure application measurement device (PAM)) and one thermal assay (CO 2 laser) were used.
Behavioural responses (skin twitch, tail flick and clamp) to stimulation at a 2x2cm test area on the
dorsal tail base were measured during test sessions at 1 day before and 3, 7, 14 and 21 days after
NGF or vehicle administration, while the pigs were kept in a test cage and accompanied by a pen
mate for social support. Within the test session each assay involved three stimulations per pig. Data
were analysed by GLM repeated measures ANOVA.
Results: NGF injection induced increased (p< 0.05) punctate mechanical sensitivity 3-7 days post
injection, compared with controls. At 14 and 21 days no significant effects on noxious sensitivity were
detected.
Conclusions: In this pilot study we showed signs of NGF-induced mechanical hyperalgesia on day 3
and 7, but the measurements of cutaneous sensitivity appeared to differ depending on the mode of
stimulation used. Further research is needed to clarify whether these findings, apparently differing
from the temporal profiles found in humans, are species differences or can be explained by
methodological differences.
811
EFFECT OF ELECTROMAGNETIC RADIATION (EMR) EMITTED FROM 3G MOBILE PHONE ON
NOCICEPTIVE BEHAVIOR IN WISTAR RAT: ROLE OF MAGNETIC FIELD
1
1
2
A. Jha , S. Jain , J. Behari , R. Mathur
1
1
2
Physiology, All India Institute of Medical Sciences, Environmental Science, Jawaharlal University,
New Delhi, India
Objective: To investigate the role of magnetic field on pain behavior of 3G frequency band exposed
wistar rat
Methods: Wistar rats were exposed to magnetic field and 3G frequency band. Tail flick latency (TFL)
and nociceptive behavior were performed at different time point of EMR exposure (Basal, 15, 30 and
45 days). Tonic pain behavior was studied at the end of exposure.
Results: There was no significant difference in TFL between 3G frequency band (5.0±0.56 and 3.9±
0.37) vs control (4.14± 0.42 and 3.8± 0.38) at basal and 45 days of exposure, respectively. However,
a significant decrease in forepaw lick-latency was observed (9.2 ± 0.78 Vs 6.0±1.16) at 45 days of 3G
frequency band exposure. Temporal pattern in nociceptive behavior of rat will be presented. Tonic
pain rating was also significantly increased specifically during the early phase while no difference
during late phase was observed between the groups. Effect of magnetic field on nociceptive behavior
of 3G frequency band exposed rat will be presented.
Conclusion: 3G frequency band exposure for 2h/day x 45 days increased the sensitivity to phasic
thermal and tonic chemical noxious stimuli.
812
CO-ADMINISTRATION OF CR4056 AND MORPHINE INDUCE ANALGESIC SYNERGY IN A RAT
MODEL OF POSTOPERATIVE PAIN
M. Lanza, F. Ferrari, I. Menghetti, D. Tremolada, G. Caselli
Pharmacology & Toxicology, Rottapharm S.p.A, Monza, Italy
We have previously reported the effect of CR4056, an I2 ligand, on mechanical hyperalgesia using
the Brennan's model of postoperative pain in the rat. In the present study we have investigated if the
efficacy of CR4056 and morphine was mutually increased when co-administrated 24 hours after the
surgical injury. This animal model was produced by a plantar incision of skin, fascia and muscle and
pain threshold determined by using the Randall-Selitto method. Since CR4056 and morphine induce
their analgesic effect with a different temporal response, we have synchronized the maximum peak
effect of each drug by administrating CR4056 1 hour before morphine. Thus, mechanical hyperalgesia
was measured 90, 180 and 360 minutes after CR4056 administration corresponding to 30, 120 and
300 minutes after morphine administration.
CR4056 (0.1-10 mg/kg, orally), morphine (0.1-10 mg/kg, subcutaneously), and their combination
produced a significant, dose-dependent analgesic effect. Isobolographic analysis revealed a
significant synergistic interaction between CR4056 and morphine. When these agents were
combined, the doses needed to reach the median effective dose were about 5-fold lower than those
seen after administration of each drug alone (ED50: 0.42 vs. 2.71 mg/kg for CR4056, 0.42 vs. 1.90
mg/kg for morphine).
CR4056 could, therefore, represent a new highly effective treatment option for postoperative pain in
patients both as stand-alone treatment and in association with morphine. CR4056, after having been
tested for pharmacokinetics and safety in healthy volunteers, is currently entering the first POC study
in humans.
813
THE EFFECT OF INHOMOGENEOUS STATIC MAGNETIC FIELD-EXPOSURE ON PAIN
RESPONSE IN AN ACUTE VISCERAL PAIN MODEL IN MICE
1
2
3
J.F. Laszlo , M. Kellermayer Jr. , K. Gyires , B. Kiss
1
2
2
Department of Computer Science, University Debrecen, Debrecen, Department of Biophysics and
3
Radiation Biology, Department of Pharmacology and Pharmacotherapy, Semmelweis University,
Budapest, Hungary
Static magnetic field (SMF)-exposure has been shown to reduce the number of acute visceral pain
responses in the writhing test in mice. We extended the present double-blind examination to entryavoidance and site preference between SMF- and sham-exposed sides with the help of a special
cage, whose part protruded in the exposure chamber of an SMF generator. Animals were free to
move in the cage within geometric limits. Typical magnetic induction values of the vertical components
of SMF were between 3 and 477 mT. We expected that beyond social effects, aversive effects and
cognitive recognition of pain inhibition would govern the locomotion of mice in the cage. Writhing
response was monitored in a 30 min period in 3 segments: 0-5, 6-20, and 21-30 min. No significant
difference was found in the side preference between exposed and unexposed sides. SMF-exposure
significantly reduced the number of writhings compared to sham-exposed (81%, p< 0.03). Exploration
dominated the ambulance of mice in the first 10 min. Deeper statistical analysis clarified that the
lateral SMF gradient between SMF and sham sides could be responsible for most of the analgesic
effect (54%, p< 0.02).
814
ENDOCANNABINOID SYSTEM MEDIATES THE ANTINOCICEPTION INDUCED BY SUCROSE
THROUGH 5-HT2A AND 5-HT2C SEROTONERGIC RECEPTORS ACTIVATION
1
2
P. Medeiros , R.L. de Freitas , N.C. Coimbra
1
2
2
Neurocience and Behavioural Sciences, Pharmacology, Medical School of the University of São
Paulo (FMRP-USP), Ribeirão Preto, Brazil
There is evidence that sweetened substances cause antinociception in rodents. It was elucidated the
involvement of the µ1-opioid, cholinergic and serotonergic non-selective receptors on the elaboration
of antinociception induced by sucrose solution. The aim of the present work was to investigate the
involvement of the endocannabinoid system in sweet substance-induced antinociception, and the role
of 5-HT2A and 5-HT2C receptors in the endocannabinoid modulation of the antinociception induced by
acute administration of sucrose in an animal model of pain. Male Wistar rats (n=6-8 per group),
weighing 250g, were submitted to the tail-flick test baseline recording and were pre-treated with
intraperitoneal (IP) administrations of RS-99544 (0.001, 0.01, or 0.1mg/kg), a selective 5-HT2A
serotonergic receptors antagonist, or RS-10221 (0.1, 0.5 or 0.01mg/kg), a selective 5-HT2C
serotonergic receptors antagonist, followed by IP-administration of cannabidiol, an endocannabinoid
receptors agonist (at 4.0mg/kg, in all cases), or vehicle. After the peripheral pharmacological
pretreatments, each animal was submitted to an oral treatment with 25% sucrose or tap water and the
nociceptive threshold was measured for 30 minutes. Sucrose administration caused sweet substanceinduced antinociception. Cannabidiol significantly increased the hypo-algesic effect of sucrose on
nociceptive thresholds. The effect of the cannabidiol increasing the antinociception induced by oral
administration of 25% sucrose was decreased by IP-administration of RS-99544 and RS-10221 (P<
0.05, in all cases). These findings suggest the involvement of the endocannabinoid system and
recruiting serotonergic receptors in the organisation of sucrose-induced antinociception. Cannabidiol
seems to mediate the sweet substance-induced antinociception through the activation of 5-HT2A and
5-HT2C serotonergic receptors.
815
CHARACTERIZATION OF THE PIG AS A CLINICALLY RELEVANT ANIMAL MODEL FOR
STUDYING INCISIONAL PAIN
1
2
2
3
D. Castel , E. Wilentz , O. Doron , O. Brenner , S. Meilin
4
1
The Neufeld Cardiac Research Institute and Dept. of Physiology and Pharmacology, Sackler School
2
3
of Medicine, Tel Aviv University, Tel Aviv, Lahav Research Institute, Kibutz Lahav, Department of
4
Veterinary Resources, The Weizmann Institute of Science, Rehovot, MD Biosciences, Neurology
Division, Ness-Ziona, Israel
Background: Management of acute pain related to surgical intervention, termed postoperative pain,
is a major problem facing physicians and patients today. While the rat plantar incision model provides
valuable data to researchers about the mechanisms driving postoperative pain, the development of
topical and localized treatment methods in this model is limited. To address these issues, a pig model
of postoperative pain has been developed. As the pig skin similarity to human is an established fact,
this model might offer better resemblance to the human condition.
Methods: After anesthesia, domestic piglets underwent left flank incisions extending either through
the skin and fascia (“full skin” incision), or the skin, fascia and muscle (“full skin and muscle” incision).
Incisions were closed and pain was assessed during recovery by application of Von Frey stimulus
(VF). Assessment occurred 3 hours post surgery and daily for an additional 7 days. IM morphine was
dosed systemically. A third group of animals received Ropivacaine HCl (Naropin) immediately prior to
wound suturing. In addition to pain levels, inflammation and wound closure were also scored.
Results: Animals incurring full skin and muscle incisions demonstrated slightly more pain than
animals that underwent full skin only incisions. Treatment with 1 mg/kg Naropin reversed pain at early
time points and significantly reversed pain for a period of 6 hours.
Conclusions: This study suggests that the pig can serve as an effective animal model for predicting
new approaches for localized treatment of postoperative pain.
816
CYCLOOXYGENASE 2 BUT NOT CYCLOOXYGENASE 1 REDUCED MECHANICAL
HYPERALGESIA IN NEONATE RATS
1
1
1
2
3
S. Reichl , S. Neuffer , D. Segelcke , S. Mertsch , P.K. Zahn , E.M. Pogatzki-Zahn
1
1
2
Department of Anesthesiology, Intensive Care and Pain Medicine, Institute of Experimental
3
Ophthalmology, University Hospital Muenster, Muenster, Department of Anesthesiology, Intensive
Care Medicine, Palliative Care Medicine and Pain Management, Berufsgenossenschaftliches
Universitätsklinikum Bergmannsheil GmbH, Bochum, Germany
Background and aims: There is considerable evidence that spinal COX-1 but not COX-2 contributes
to mechanical hyperalgesia after incision (1). However, in young rats (14 days old), COX-1 is not
relevant (2, 3). We therefore hypothesized, that spinal COX-2 plays a role for incision-induced
mechanical hyperalgesia in young rats.
Methods: Rat pups (P5; P14; n=55) underwent plantar incision; mechanical withdrawal thresholds
(WT, calibrated von Frey filaments) were assessed before and after incision and after IT
administration of SC-560 (COX-1 inhibitor), or NS-398 (COX-2 inhibitor) or vehicle. In 36 rats, spinal
expression of COX-1 and COX-2 after incision was investigated by immunohistochemistry and realtime PCR.
Results: IT administration of NS-398 but not SC-560 significantly reversed the decreased WT after
incision in 5-day-old rats (p< 0.05 vs vehicle). In 14-day-old animals IT injection of SC-560 or NS-398
did not modify WT. Spinal COX-1/2 immunoreactivity was unchanged after incision (P5; P14). There
was a slight increase of spinal COX-2 mRNA in P5 rats after incision. Spinal COX-1 mRNA
expression was unchanged in P5 and P14 rats after incision.
Conclusion: We show for the first time, that spinal COX-2 but not COX-1 is involved in transmission
of incision-induced mechanical hyperalgesia in neonate (5 day old) rats; in P14 rats, neither COX 1 (in
congruence to ref. 3) nor COX-2 is relevant. There is a developmental switch from COX-2 to COX-1
that occurs between P14 and P28 (2, 3).
(1) Anesth Analg 2005; 100:1390-3
(2) Anesthesiology. 2006 Mar;104(3):426-31.
(3) Anesthesiology 2004; 101:1031-5
817
TRAMADOL, KETAMINE OR GABAPENTIN, PREVENT LATENT PAIN SENSITISATION (LPS) IN
A MOUSE MODEL OF POSTOPERATIVE PAIN
E. Romero-Alejo, A. Romero, M.M. Puig
Pain Research Unit, Dept. Anaesthesiology, IMIM- Parc de Salut Mar. Universitat Autònoma de
Barcelona, Barcelona, Spain
Background and aims: Surgery induces postoperative hyperalgesia (POH) lasting 4-7 days that is
re-established after a challenge with (-)naloxone; the neuroplastic changes responsible for this
delayed effect are known as LPS, and could be related to the development of chronic post-surgical
pain (CPSP). We investigated the preventive effects of likely anti-hyperalgesic drugs in an incisional
model of post-operative pain.
Methods: We assessed the effects of a single intraoperative dose of the following anti-hyperalgesics
on POH and LPS: dexketoprofen (100mg/kg), tramadol (100mg/kg), gabapentin (100mg/kg),
minocicline (50mg/kg), ketamine (50mg/kg), A-836339 (CB2 agonist, 30mg/kg) and midazolam (4
mg/kg). Mechanical POH (Von Frey) was assessed 4h, 1d, 20d and 21d postoperatively. On day 21, a
challenge with naloxone (1mg/kg) was administered. Statistical analysis: ANOVA and Student's t-test.
Results: Dexketoprofen completely prevented POH (day 1), but did not modify LPS. Tramadol
reduced (p< 0,001) POH and LPS by 30% and 46%, respectively. Similarly, gabapentin and ketamine
significantly decreased both POH and LPS, although ketamine had a more pronounced effect
decreasing LPS (60%). No significant effects were observed on POH or LPS after A-836339,
minocicline or midazolam. The global effect of the treatments assessed by the AAC (0-21days) shows
similar results.
Conclusions: Dexketoprofen could be useful in the management of POH altough does not prevent
LPS. Tramadol, gabapentin or ketamine decrease POH and partially prevent LPS, suggesting that
they could be clinically useful preventing the development of CPSP.
Supported by: FIS PS09/01270 and the Endowed Chair in Pain Management UAB- Parc de Salut
Mar- Menarini (MMP-4306900001).
818
THE EFFECT OF L-MENTHOL ON SKIN HYPERALGESIA INDUCED BY THE LOCAL IRRITANT
TRANS-CINNAMALDEHYDE
H.H. Andersen, H.G. Møller, R.V. Olsen, P.W. Eskelund, L. Arendt-Nielsen
Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of
Medicine, Aalborg University, Aalborg, Denmark
Background and aims: L-menthol has historically been used as a topical counterirritant and a mild
analgesic, effective on inflamed or sensitized skin areas. However, applying high-concentration Lmenthol to the skin of healthy humans leads to cold hyperesthesia and mechanical hyperalgesia.
Studies have indicated that a preexisting sensitization or pain condition is necessary to facilitate the
counterirritant properties of L-menthol. The aim of this study was to evaluate the effect of L-menthol
on skin hyperalgesia provoked by the local irritant trans-cinnamaldehyde (CA). The effect was
assessed by superficial skin perfusion, skin temperature, axon-reflex-flare and mechanical pain
sensitivity (MPS).
Methods: Four solutions were investigated in 10 healthy subjects: 98% ethanol (vehicle of all
substances), 40% L-menthol, 10% CA and a combination of 40% L-menthol and 10% CA. The
substances were applied to the volar forearm for 20 min. Infrared thermography, Laser Doppler
flowmetry and MPS were investigated before and after substance-application during two experimental
sessions.
Results: Topical 10% CA caused a significant increase in MPS, skin temperature, perfusion, axonreflex-flare and is subjectively described as burning, hot and pinprick-like. Co-administration of 40% Lmenthol significantly decreased skin temperature and the area of axon-reflex-flare but did not alleviate
mechanical hyperalgesia nor the increased perfusion in the area of CA administration.
[Area of axon-reflex-flare]
Conclusions: High-concentration L-menthol efficiently reduces the increased skin temperature and
axon-reflex-flare caused by CA-mediated C-fiber activation, but had no significant analgesic effect on
MPS or subjective pain descriptors.
819
ACID-INDUCED EXPERIMENTAL KNEE PAIN AND HYPERALGESIA IN HUMANS
1
1
1
2
1
T. Asaki , K. Wang , Y. Luo , T. Arendt-Nielsen , T. Graven-Nielsen , L. Arendt-Nielsen
1
1
2
Dept of Health Science and Technology, Aalborg University, Aalborg, Denmark
Background and aims: Animal studies have demonstrated that acid stimulation induces muscle pain
and hyperalgesia, suggesting that acidity plays a role in musculoskeletal pain. The aims were to
investigate 1) if local pain or hyperalgesia is induced by an acidic infusion into the fat pad of knee in
humans, 2) if referred pain is evoked, and 3) if gender difference is present.
Methods: Fourteen healthy men and 16 age-matched women participated. Buffered acid saline with
pH5 and pH7.4 were infused into the fat pad of the knee in 2 separate sessions. In addition, repeated
infusions were performed in 14 subjects with 2 days interval. Subjects were asked to rate the pain
intensity on a visual analogue scale (VAS, 0-10). Pressure pain threshold (PPT), pinprick, thermal
pain threshold over both knees were tested before, during, and after the infusion.
Results: The maximal VAS score was significantly higher in the pH5 compared with the pH7.4
session (5.6±0.3 and 2.0±0.3, P< 0.001), without gender differences. The referred pain was not
observed in most of the subjects after single or repeated infusion. PPTs around the stimulated knee
were significantly decreased in pH5 session during and after the infusion (P< 0.001). Pinprick and
thermal pain thresholds were not significantly changed. Facilitation of pain or hyperalgesia in the
repeated infusions was not observed.
Conclusions: Acidic infusion induces tonic local pain and hyperalgesia around deep tissues in
human knee, but widespread hyperalgesia was not observed after repeated infusions in contrast with
animal studies.
820
PAIN THRESHOLDS AND FATIGUE IN HEALTHY SUBJECTS: THE EFFECT OF TIME-OF-DAY
J. Aviram, T. Shochat, D. Pud
Faculty of Social Welfare and Health Sciences, Haifa University, Haifa, Israel
Background and aims: Pain and fatigue are complex affective, sensory, and cognitive phenomena.
Compelling evidence show reciprocity between sensitivity to pain and fatigue in patients with chronic
pain conditions, and both are affected by time-of-day.
There is a lack of studies on these associations in pain free subjects. The present study aimed to
assess time-of-day effects on experimental evoked pain and fatigue in healthy subjects in order to
increase the understanding of the net effect of the relationship between pain and fatigue without
chronic pain confounders.
Methods: Forty-five healthy men were tested in the morning and evening in this cross over random
order study. Mechanical (pressure algometer), heat (TSA) and cold (TSA and CPT) pain thresholds
(PT) as well as fatigue levels (Lee Fatigue Scale) were assessed in each session. Hierarchical
clustering and K-means cluster analysis was used to identify subgroups of subjects according to the
four standardized PTs at each time of day.
Results: Subjects were grouped as low or high PT cluster members. The subgroup of low PT
included 50% of the subjects in the morning and 86% in the evening. Fatigue levels were significantly
higher in the low PT subgroup in both morning and evening (p=0.01, for both).
Conclusions: Sensitivity to pain is characterized by high level of fatigue and is more prevalent in the
evening. Sub-grouping subjects based on their sensitivity to pain may be useful for identifying the
inter-individual variability in pain perception and provide valuable information for future clinical trials
on chronic pain patients.
821
MITOCHONDRIAL MODULATORS AND PERSISTENT OROFACIAL PAIN IN MICE
1,2
1
1
1
1
A. Dondas , T. Alexa , A. Luca , D. Negru , I. Chiriac , C.R. Bohotin
1
1
Centre for the Study and Therapy of Pain, University of Medicine and Pharmacy 'Gr T Popa',
Cardiovascular Surgery, Institute of Cardiovascular Diseases 'Prof. Dr. George I.M. Georgescu', Iasi,
Romania
2
Background: Mitochondrial modulators like methylene blue (MB) - which increases mitochondrial
complexes I-IV activity; disulfiram (DS) - an inhibitor of mitochondrial aldehyde dehydrogenase, and
Vitamin C (VitC) - a redox modulator, were used.
Aim: To investigate the effect of chronic administration of mitochondrial modulators on inflammatory
pain in mice.
Methods: Thirty-two BALB/c male mice were divided into 4 groups that received daily intraperitoneal
injections with MB - 5 mg/kg for 14 days; VitC - 500 mg/kg, saline 0.2 ml/ mice for 21 days. The DS
group received by oral gavage every other day 50 mg/kg DS for 3 weeks. At the end of the treatment,
mice received 20 µL of 5% formalin into the whisker pad. The intensity of the pain was assessed by
counting the time mice spent rubbing the injected area. The results were analyzed using one-way
ANOVA and unpaired Student´s t-test.
Results: Two weeks after MB administration there was a significant analgesic effect on both phases
of the formalin-induced pain (p=0.001, p=0.008). After 3 weeks of DS or VitC administration, there
were no significant modifications on the second phase for both substances and on the first phase for
VitC. A significant decrease on the first phase for DS (p=0.006) was registered.
Conclusion: Our results show that the mitochondrial modulators used in this study have different
effects on orofacial pain and on the peripheral and central components of formalin-induced pain.
Acknowledgements: Research supported by Executive Agency for Higher Education and Research
Funding (UEFISCSU) Romania project PN-II-ID-PCE-2011-3-0875.
822
A NOVEL EXPERIMENTAL MODEL OF BONE HYPERALGESIA AFTER MECHANICAL IMPACT
PERIOST STIMULATION
S. Finocchietti, T. Graven-Nielsen, L. Arendt-Nielsen
Aalborg University, Aalborg, Denmark
Background and aims: Bone pain and hyperalgesia are involved in many pain disorders. The
fundamentals of bone associated pain and hyperalgesia are still not fully understood. This study
aimed to develop a human experimental model of bone hyperalgesia provoked by standardised
mechanical impact periost stimulation.
Methods: Bone hyperalgesia was induced by different weights impacted on the shinbone in sixteen
healthy subjects. The mechanical impact pain threshold (IPT) was measured as the height from which
three weights (165g, 330g, 660g) should be dropped to elicit pain. Temporal summation of pain to
repeated impact stimuli (3 s inter-stimulus interval, 120%IPT) was assessed by scores of the evoked
pain intensity on a Visual Analogue Scale (VAS). IPT and temporal summation were recorded before,
24h, 72h, and 96h after the first impact stimulations. IPT were determined from five locations along
the tibia bone.
Results: The IPTs were reduced 24h after hyperalgesia induction for all weights and the effect lasted
up to 72h (P< 0.05). Repeated impact stimuli caused progressively increasing VAS scores and the
temporal summation was significantly facilitated after induction of hyperalgesia (P< 0.05). No
statistical difference was found among the five locations along the tibia.
Conclusions: Bone hyperalgesia was efficiently induced by repeated mechanical impact periost
stimulation on the shin bone. The developed model may provide the basis for studying the
fundamentals bone pain mechanism in humans and be used for profiling analgesic or antiinflammatory compounds developed for this target.
823
CUTANEOUS SENSITIZATION BY TOPICAL CAPSAICIN ALTERS CUTANEOUS VASOMOTOR
RESPONSES TO LOCAL CONTROLLED HEAT APPLICATION: A HUMAN EXPERIMENTAL
STUDY
1
1
1
T.A. Nielsen , L.B. da Silva , L. Arendt-Nielsen , P. Gazerani
2
1
Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty
2
of Medicine, Health Science and Technology, Aalborg University, Aalborg, Denmark
Background and aims: Cutaneous heat application provokes a transient vasomotor response. It was
not known whether this phenomenon can be facilitated by skin sensitization. Hence, the present study
was designed to test if cutaneous sensitization by topical application of capsaicin can alter size,
duration and spatial extension of a heat-evoked vasomotor response and whether men and women
respond differently.
Methods: Thirty healthy Caucasians (15 women, 15 men) were recruited. Vasomotor responses were
evoked by application of heat (43°C, 60 sec) on one volar forearm. Changes in cutaneous
temperature were monitored by thermography and alterations in blood flux by laser speckle contrast
imaging. Afterwards, capsaicin cream (1%, 30 min) was applied on one forearm to induce cutaneous
sensitization. The mirror forearm served as control site. Alterations in heat-evoked vasomotor
changes following capsaicin-induced sensitization were recorded for 30 minutes in five regions of
interest up to 10 cm away from the site of capsaicin application.
Results: Capsaicin-induced skin sensitization facilitated heat-evoked vasomotor reactions. Skin
temperature was elevated significantly higher in women than men (P< 0.05) and the alteration lasted
longer. However, regional expansion of the change was greater in men. Following sensitization,
women showed stronger and spatially more extended blood flux responses compared with men.
Conclusions: Capsaicin-induced sensitization led to gender-specific alterations in heat-evoked
vasomotor responses in terms of size, duration, and spatial distributions. A ceiling effect was
observed in this facilitation phenomenon most likely due to capsaicin-induced neurogenic
inflammation. Findings from this study may contain potential applications for topically applied drugs.
824
A-FIBER-INHIBITION OF THE SUPERFICIAL RADIAL NERVE - SOMATOSENSORY PROFILE OF
A HUMAN SURROGATE PAIN MODEL
1
1
1
1
2
2
1
F. Mahn , J. Höper , M. Tomforde , O. Klebe , T. Klein , D. Pfau , R. Baron , A. Binder
1
1
Department of Neurology, Division of Neurological Pain Research and Therapy, Christian-Albrechts2
Universität, Kiel, Department for Neurophysiology, Center for Biomedicine and Medical Technology
Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany
Background: Induction of cold hyperalgesia due to central disinhibition by A-fiber-blockade of
peripheral nerves has been introduced as a human surrogate pain model years ago.
Methods: In an open, two-center study in 24 healthy subjects A-fiber-blockade of the left superficial
radial nerve was induced by applying pressure at the wrist. Before, during and after blockade,
quantitative sensory testing (QST) was performed using standardized protocol of the German
Research Network on Neuropathic Pain (DFNS). Somatosensory profiles were created by calculating
z-scores.
Results: In the entire group, A-fiber-blockade induced significant increase of cold detection threshold
(CDT; p=0.001) and thermal sensory limen (TSL) indicating cold hypoesthesia (p< 0.001). Paradoxical
heat sensations (PHS) occurred (p< 0.001). Cold pain threshold was decreased due to 15 subjects
revealing cold hyperalgesia, but not significantly (p=0.317). Mechanical detection threshold (MDT; p<
0.001), mechanical pain threshold (p< 0.001), mechanical pain sensitivity (p< 0.001) and pressure
pain threshold were increased (p=0.001), indicating loss of A-fiber function. Subgroup analysis of
subjects without cold hyperalgesia showed significant increase for CDT (p< 0.001), TSL (p=0.003),
MDT (p=0.003) and vibration detection threshold (VDT; 0.011) and less frequent PHS (p=0.021)
compared with subjects developing cold hyperalgesia.
Conclusions: A-fiber-blockade of the superficial radial nerve induced cold and mechanical
hypoesthesia, occurrence of PHS and mechanical hypoalgesia. 15 subjects showed cold
hyperalgesia. Subgroup analysis may lead to the conclusion that induction of cold hyperalgesia in this
model requires preserved A-fiber-function to a certain extent.
Acknowledgements: Supported by Bundesministerium für Bildung und Forschung (BMBF, Grant
01EM0903 for DFNS).
825
IMPAIRED POSTURAL CONTROL BY ACUTE EXPERIMENTAL LOW BACK PAIN
1
2
1
M.K. Sohn , S. Kang , S.J. Jee , P.S. Hwang
1
1
2
Rehabilitation Medicine, Chungnam National University, Physical Medicine and Rehabilitation, Sun
General Hospital, Daejeon, Republic of Korea
Objective: To evaluate the changes in static and dynamic postural control after development of an
acute low back pain.
Subjects and method: Thirty healthy right-handed volunteers were divided into three groups; a right
back pain group, a left back pain group and a control group. 0.5 ml of 5 % hypertonic saline was
injected into L4-5 paraspinal muscle over 5 s to cause a muscle pain. The movement of the center of
gravity (COG) during their static and dynamic postural control was measured with their eyes open and
with their eyes closed before and 2 min after the injection.
Results: The COGs of healthy adults were shifted to the right quadrant and the posterior quadrant
during their static and dynamic postural control test (p< 0.05). The instability index during eyes closed
was significantly increased than that during eyes open both the static postural and the dynamic
postural control test in both conditions with and without acute back pain(p< 0.05). After the pain
induction, their overall and anterior/posterior instability was increased in both the right back pain
group and the left back pain group during static postural control test (p< 0.05). A right deviation and a
posterior deviation of the COG still remained with a posterior deviation being greater in the right back
pain group (p< 0.05).
Conclusion: The static instability, particularly the anterior/posterior instability was increased during
presence of the acute low back pain, regardless of the visual information and the pain location.
826
108/158
THE EFFECTS OF COMMON COMT VARIANTS RS4680(VAL
MET) AND FUNCTIONAL
RS4633-RS4818-RS4680 HAPLOTYPES ON EXPERIMENTAL PAIN ARE MODULATED BY
3´UTR-SNP RS887200
O. Kambur
1,2,3
4,5
, M.A. Kaunisto , E.A. Kalso
1,6
1
Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital,
Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki,
3
4
Department of Pharmacology, Institute of Biomedicine, Institute for Molecular Medicine Finland
5
(FIMM), University of Helsinki, Folkhälsan Institute of Genetics, Folkhälsan Research Center,
6
Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland
2
Background and aims: Polymorphisms in COMT-gene modulate COMT-activity and sensitivity to
108/158
pain. In our previous study in breast cancer patients SNPs rs4680 (Val
Met) and functional
rs4633-rs4818-rs4680 haplotypes did not show predicted effects whereas the strongest effects on
pain phenotypes were seen for SNP rs887200 located in the 3´UTR adjacent region.
The effects of common COMT variants on pain can be affected by variants in other genes (Lötsch
2009). We hypothesized that also the variants within the COMT gene, such as rs887200, can act as
confounders modulating the effects of rs4680 and functional haplotypes. The aim of our study was to
analyse their possible interactions with rs887200.
Methods: Cold water test was performed in 900 patients scheduled for breast cancer surgery. The
interactions between rs887200, rs4680 and rs4633-rs4818-rs4680-haplotypes were assessed by
epistatic interaction analysis and 2-way ANOVA.
Results: There was an epistatic interaction between rs887200 and CCG-haplotype. In all cases the
CCG/CCG-haplotype was accompanied by the C/C-variant of rs887200, both contributing to the
decreased pain intensity. Rs887200 also showed interaction with the TCA-haplotype decreasing cold
pain intensity.
The effect of rs4680 on pain intensity and tolerance during the cold water test was assessed
separately in rs887200C- and rs887200T-homozygotes. In both groups the effect of rs4680 was
evident and statistically significant (2-way RM-ANOVA, effect of genotype, CC, p< 0.01, TT, p<
0.0001).
Conclusions: Rs887200 modulates the effects of rs4680 and rs4633-rs4818-rs4680-haplotypes on
cold pain. Once the effect of rs887200 is controlled, the effects of other genotypes on pain follow the
predicted COMT-activity.
827
COMPLEX MUSCULAR ADAPTATION TO PERTURBATIONS AFTER INDUCTION OF
EXPERIMENTAL LOW BACK PAIN IN HEALTHY PARTICIPANTS
1,2
1
L.H. Larsen , R.P. Hirata , T. Graven-Nielsen
1
1
2
Center for Sensory-Motor Interaction, Aalborg University, Department of Physiotherapy, University
College of Northern Denmark, Aalborg, Denmark
Background and aims: Spine stability is affected in low back (LB) pain and potentially by muscle
fatigue and soreness. This study assessed standing motor control responses to unexpected surface
perturbations during experimental LB muscle pain combined with fatigue and muscle soreness.
Methods: Nineteen healthy participants were examined day 1-3 before and after bilateral injections of
hypertonic saline into m. longissimus. Pain intensity was scored on visual analogue scale (VAS). Day
2 included injections post-exercise LB muscle fatigue and day 3 during delayed onset back muscle
soreness (DOMS). Twenty perturbations were conducted randomly: tilts in sagittal and frontal or
displacements in the frontal plane. Bilateral electromyography (EMG) was recorded from 12 trunk
muscles. The root-mean-square (RMS-EMG) was extracted. Changes (DeltaRMS) and absolute
changes (DeltaRMSabs) in the RMS-EMG from the baseline of the day were calculated and averaged
among back and abdominal muscles.
Results: VAS scores during fatigue and DOMS were significantly higher compared with day-1 (P<
0.01). Back muscle RMS-EMG decreased and abdominal muscle RMS-EMG increased during
DOMS, compared with pain-free conditions (P< 0.01). Experimental LB pain increased DeltaRMS in
the abdominal muscles day 1 (P< 0.01) and in the fatigued back muscles day 2 (P< 0.01). Pain
increased DeltaRMSabs in day 1-3 in both muscle groups compared to baseline (P< 0.01) with a
minor effect of pain in the DOMS condition (P< 0.01).
Conclusions: Pain-related reorganization may challenge spine stability during motor tasks in acute
pain conditions and this seems to be even further implicated after fatigue and muscle soreness.
828
PERIPHERAL CYTOKINE RESPONSE TO BURN INJURY IN HUMANS: A MICRODIALYSIS
STUDY
H. Laycock, C. Bantel, I. Nagy
Anaesthetics, Pain Management and Intensive Care, Imperial College London, London, UK
Background: Pain associated with burn injury presents a major clinical challenge (Summer 2007)
and can lead to chronic pain, psychological issues and decreased social re-integration. Burn injury
causes major tissue damage and an inflammatory response (Laycock 2013) leading to the
accumulation of a complex milieu of biological agents. These likely sensitise a subset of primary
sensory nerve fibres (Gold 2005) leading to pain. However the composition of this milieu is
incompletely defined.
Aim: To investigate cytokine and chemokine response in two human models of burn injury.
Methods: Ten healthy volunteers received either a transient thermal or topical chemical (capsaicin)
injury (n=5 per model) imparted on their non-dominant forearm. Each was mapped for erythematous
flare, hyperalgesia and allodynia. Dermal microdialysis was performed in the injury and a control area
of the arm (diasylate samples collected between 60 and 120 minutes after probe insertion). Samples
were analysed using a 41 multiplex microbead array assay (MILLIPLEX® MAP using Luminex
xMAP®).
Results: Both models produced erythematous flare, primary and secondary hyperalgesia and
allodynia, mimicking burn injury associated sensory changes. Differential cytokine profiles occurred
both between the injury and control diasylate samples and additionally between the different injury
models. Thermal injury showed increased IL1α compared with control and IL6 and CCL11 increase in
chemical injury.
Conclusions: Inflammatory mediators present at 120 minutes following experimental injury in human
volunteers differed based in injury mechanism. It may be that targeting research into inflammatory
mechanisms in burn injury may help streamline personalised analgesic management in the future.
829
INTERACTION BETWEEN EXPERIMENTAL CUTANEOUS AND MUSCLE HYPERALGESIA: AN
EXPERIMENTAL STUDY IN HEALTHY VOLUNTEERS
1
1,2
1
1
1
S. Lo Vecchio , L.J. Petersen , S. Finocchietti , P. Gazerani , L. Arendt-Nielsen , T. Graven1
Nielsen
1
2
Aalborg University, Aalborg University Hospital, Aalborg, Denmark
Background and aims: Cutaneous hyperalgesia is prominent in the Ultraviolet-B (UVB) model of
inflammatory pain and hyperalgesia. There is no evidence indicating whether muscle pain and
hyperalgesia via somatic convergence affects the sensitivity of UVB- induced cutaneous
hyperalgesia. This study aimed to investigate whether muscle hyperalgesia affects the UVB-induced
cutaneous hyperalgesia.
Methods: Skin areas (3x4cm) on one side of the upper trapezius and lower back of 16 healthy
volunteers were UVB irradiated (3xMinimal-Erythema-Dose). At the same day subjects performed
eccentric exercise to induce delayed onset muscle soreness (DOMS) in the low back in order to
provoke muscle hyperalgesia. Inside and outside the UVB treated sites and at the mirrored
contralateral sites the assessments were performed before and one day after irradiation:
1) Superficial blood flow (Laser Doppler imaging);
2) Weight-calibrated cutaneous pin-prick thresholds;
3) Pressure pain thresholds (PPT) recorded by computer-controlled pressure algometer (2 cm
probe).
2
Results: Compared with before exercise the low back site without irradiation demonstrated DOMS
(mean score: 2.5) with significant reduced PPTs. After irradiation and exercise, cutaneous blood flow
showed a significant increase (P< 0.01) inside and outside the irradiated area in both UVB and
UVB+DOMS sites with a significant lower increase in the UVB+DOMS site compared with UVB site
alone. Pin-prick pain and pressure pain thresholds were significantly decreased within the irradiated
area (P< 0.01) regardless of DOMS.
Conclusions: The muscle hyperalgesia reduced the UVB-related vasodilatation without affecting the
UVB-related cutaneous and deep-tissue hyperalgesia. These data suggests an interaction between
cutaneous and deep-tissue hyperalgesia.
830
A FOVEA FOR PAIN AT THE FINGERTIPS
1
1
2
3
1
F. Mancini , C. Sambo , J.D. Ramirez , D.L. Bennett , P. Haggard , G.D. Iannetti
1
2
1
3
University College London, King's College London, London, Oxford University, Oxford, UK
The spatial resolution of sensory systems is not homogeneous across their receptive surfaces. For
example, tactile acuity is greatest on the fingertips, where mechanoreceptive fields are plentiful and
small. In contrast, pain is considered to lack any equivalent to the tactile fovea on the fingertips,
where the density of nociceptive fibers is remarkably low. Here, by combining psychophysics with
histology, we show that this established notion is incorrect. By delivering small-diameter nociceptivespecific laser pulses to human volunteers, we discovered that (1) the spatial acuity for pain is higher
on the fingertips than on proximal skin regions such as the hand dorsum, and (2) this distal-proximal
gradient for pain is comparable to that for touch. In contrast, skin biopsies in the same participants
showed that the intraepidermal nerve fiber density is lower in the fingertips than in the hand dorsum.
The increased spatial acuity for pain on the fingertips therefore cannot be explained simply by
peripheral innervation density.
831
THE EFFECT OF SLEEP RESTRICTION ON CORTICAL EVOKED RESPONSES TO PAINFUL
ELECTRICAL STIMULATION IS GENDER DEPENDENT
1
1,2
1,3
1
4
D. Matre , L.A. Viken , I.B. Hjelle , J.T. Stuenæs , L. Hu , K.B. Nilsen
1,5,6
1
Dept of Work Psychology and Physiology, National Institute of Occupational Health, Oslo,
3
Norwegian University of Science and Technology, Trondheim, Norwegian University of Life
4
5
Sciences, Ås, Norway, School of Psychology, Southwest University, Chongqing, China, Department
6
of Neurology, Oslo University Hospital, Oslo, Department of Neuroscience, Norwegian University of
Science and Technology, Trondheim, Norway
2
Background and aims: Adequate quantity and quality of sleep is essential to maintain health and
daytime functioning. We have investigated the effect of sleep restriction on cortical evoked responses
to painful stimuli.
Methods: Responses to painful electrical stimuli (custom made platinum electrode) after normal sleep
and after two nights of 50 % sleep restriction were recorded in 22 healthy subjects (8 men and 14
women) aged 18-31yr (mean 23 ± 4) with a within-subject crossover design. Responses were
obtained both subjectively and as cortical event related responses (ERP) using active electrodes
(Brain Products). ERPs (measured at electrode Cz, linked ear reference) were analyzed with both
time-domain (N2P2 amplitudes) and with time-frequency domain (0.5-20Hz /0-200ms). A linear mixed
model with random intercept was used.
Results: Subjective responses to painful electrical stimulation increases after sleep restriction (p =
0.019). A significant sleepxgender interaction was found for the cortical evoked responses (p ≤ 0.002).
For women, ERPs were unchanged after sleep restriction using time-domain averaging (p = 0.827),
but was increased after sleep restriction using time-frequency analysis (p = 0.003). For men, ERPs
were reduced using time-domain averaging (p < 0.001), but unchanged after sleep restriction for the
time-frequency analyses (p = 0.115).
Conclusion: The effect of sleep restriction on cortical evoked responses to painful stimuli is different
between men and women, and is also dependent on the features identified with the different analysis
domains (time vs. time-frequency). Earlier findings of increased subjective responses to painful stimuli
after sleep restriction were confirmed.
832
FINITE ELEMENT SIMULATIONS OF SKIN TEMPERATURE AT THE BASAL EPIDERMAL
LAYERS PREDICT THE THERMAL DETECTION THRESHOLD OF AΔ- AND C-FIBERS
1
1
2
A. Mouraux , L. Plaghki , F. Henrotte , E. Marchandise
1
2
2
Institute of Neuroscience, Institute of Mechanics, Materials and Civil Engineering, University of
Louvain, Brussels, Belgium
Background: Infrared laser stimulation of the skin is currently the most reliable method to elicit
responses related to the activation of nociceptors in humans. However, fine characterization of the
nociceptive stimulus requires knowledge of the spatio-temporal skin temperature profiles generated
by the laser. Recently, using a novel CO2 laser stimulator to deliver short-lasting (ms) constanttemperature heat pulses through a feedback regulation of laser power by surface skin temperature,
we showed that an adaptive staircase algorithm using reaction-time to distinguish between responses
triggered by Aδ- and C-fibres can be used to estimate reliably the surface skin temperature required
to elicit Aδ- and C-fibre related detections.
Methods: Here, using Finite Element simulations of skin heating taking into consideration the
variability of water content across skin layers, we examined whether the thermal detection threshold
of Aδ- and C-fibres was more closely related to the spatio-temporal temperature profiles in the basal
epidermal layers, i.e. where most heat-sensitive free nerve endings are located.
Results: Using the same adaptive staircase algorithm combined with stimuli of varying duration (25200 ms) and beam diameter (6-12 mm), we found that the surface skin temperature required to elicit
Aδ- and C-fiber detections was strongly dependent on the duration and on the surface area of the
stimulus. In contrast, the estimated skin temperature in the basal epidermal layers that predicted Aδand C-fiber detections was independent of stimulus duration and surface area.
Conclusions: Taken together, our results suggest that Finite Element simulations better characterize
the response properties of heat-sensitive nociceptors.
833
PHYCHOPHYSICAL ALTERATIONS INDUCED BY SENSITIZATION OF COLD-RECEPTORS
TRPM8 AND TRPA1
R.V. Olsen, P.W. Eskelund, H.G. Møller, H.H. Andersen, L. Arendt-Nielsen
Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of
Medicine, Aalborg University, Aalborg, Denmark
Background and aims: TRPM8 and TRPA1 mediate innocuous and noxious cold sensation
respectively and may be involved in clinical conditions i.e. cold allodynia and hyperalgesia. Using Lmenthol and trans-cinnamaldehyde (CA) it is possible to study the sensory alterations related to
sensitization of each receptor complex. Studies have found that while CA induces heat hyperalgesia
but has no effect on cold pain threshold (CPT), L-menthol significantly increase CPT, but has no effect
on heat pain threshold (HPT). These results indicate that the receptors have wider functional
properties than previously assumed. The aim of this study was to assess the sensory modulatory
effects of TRPM8 and TRPA1 sensitization using quantitative sensory tests (QST).
Methods: 10 healthy subjects were recruited. Three substances were investigated: 98% ethanol
(vehicle), 40%L-menthol and 10%CA. The substances were applied to the volar forearm for 20 min.
The QST-battery included: cold detection threshold (CDT), CPT, warmth detection threshold (WDT),
HPT, cold hyperalgesia (CHA), heat hyperalgesia (HHA).
Results: L-menthol and CA increased CDT while only L-menthol significantly increased CPT. Both
substances decreased WDT and HPT with significant difference in HPT between L-menthol and CA.
CHA was induced by L-menthol while HHA was induced by both L-menthol and CA. Both substances
decreased MPT equally. TSL was significantly decreased by CA but unaffected by L-menthol.
Conclusions: Both substances induce multimodal sensory alterations. CA primarily induces heat
hyperesthesia while L-menthol consistently induces cold hyperesthesia indicating that the assumption
of TRPA1 as a noxious cold receptor and TRPM8 innocuous cold receptor needs further
investigations.
834
SYNOVIAL FLUID (SF) IL-6 AND SOLUBLE IL-6 RECEPTOR INTERACTION IN ACUTE PAIN
AFTER KNEE SURGERY
1,2
3
4
4
L.A. Rosseland , A.-L. Lind , D. Wu , M. Kamali-Moghaddam , T. Gordh
1
3,5
2
Division of Emergencies and Critical Care, Oslo University Hospital, Institute of Clinical Medicine,
3
Faculty for Medicine, University of Oslo, Oslo, Norway, Department of Surgical Sciences,
4
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala
5
University, Pain Clinic, Uppsala University Hospital, Uppsala, Sweden
Background and aims: Upregulation of IL-6 correlates with acute inflammatory pain. The natural
pain intensity course and SF samples can be collected from patients after knee arthroscopic
procedures in general anesthesia. The aim of this analysis was to compare perceived pain and local
inflammatory biomarkers.
Methods: Ten patients for knee arthroscopy under general anesthesia were observed for
development of acute pain after surgery. No prophylactic analgesics were given. Frequent pain
intensity verbal ratings (no, mild, moderate, severe and very severe) were performed. SF was
collected when the patient needed analgesics (moderate-to-severe pain) or at discharge after 2 h with
only no or mild pain. SFs (1µL pr patient) were analyzed by antibody based multiplex immunoassay.
Output data is normalized and delivered as log2 base ΔΔCq values (Proseek Multiplex panel, OLINK,
Uppsala, Sweden).
Results: Mean SF IL-6Rα was 2.83 ΔΔCq (0.71) in patients with no or mild pain and 1.80 ΔΔCq
(0.49)(p= 0.025) in patients with moderate to severe pain after knee arthroscopy. Mean IL-6 was 6.73
ΔΔCq (2.39) and 4.03 ΔΔCq (3.20), respectively.
Conclusions: Higher soluble IL-6Rα ΔΔCq in patients with no or mild pain compared to patients with
moderate to severe pain was unexpected. The interaction between IL-6 and sIL-6Rα is not fully
understood. Increased IL-6R in peripheral tissue may act anti-inflammatory and antinociceptive. The
interpretation in this pilot study is limited by a small number and inter-individual differences in the
timing of SF collection.
835
COMBINED NGF-SENSITIZATION AND UVB-INFLAMMATION AS AN EXPERIMENTAL MODEL
FOR SPONTANEOUS PAIN IN HUMANS
R. Rukwied, B. Weinkauf, M. Main, O. Obreja, M. Schmelz
Dept. of Anesthesiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Background and aims: Antibodies capturing nerve growth factor (NGF) are analgesic in chronic
inflammatory pain without reducing inflammation. We hypothesized that sensitization and ongoing
pain by inflammatory mediators is increased when the skin has been pre-sensitized with NGF.
Methods: 13 male subjects received i.d. 1 µg NGF into the lower leg. UV-B irradiation (1 cm², 3-fold
MED) was performed 21 days later. Sensitization to mechanical, thermal and electrical stimuli was
assessed at days 21 - 22 - 24 - 28 - 35 - 49 - 70 after NGF-injection in (1) native, (2) NGF-sensitized,
(3) UV-B irradiated (days 22-70 only) and (4) NGF/UV-B treated skin (days 22-70 only).
Results: UV-B irradiation of NGF pre-sensitized skin caused spontaneous pain in about 70% of the
subjects. Hyperalgesia (VAS, 0-100) was additive after combined NGF/UV-B versus single NGF- or
UV-B-treatment for electrical, mechanical impact and tonic heat stimuli and paralleled the intensity of
UV-B inflammation. Ratings to tonic mechanical pressure (100 kPa, 10 sec) and pin prick (150 mN, 5
sec) increased in a supra-additive manner at 24 h after irradiation. After 48 h, heat and electrical
sensitization by UV-B alone remained increased, but supra-additive hyperalgesia to tonic pressure at
the NGF/UV-B spot had subsided. Hyperalgesia and spontaneous pain coexisted in NGF/UV-B
treated skin, but did not correlate significantly.
Conclusions: NGF sensitizes nociceptive endings such that inflammatory mediators may cause a
sufficient excitation to provoke spontaneous pain. Neuronal sensitization and level of inflammation
may represent independent therapeutic targets in chronic inflammatory pain conditions.
836
HOW SPATIALLY PRECISE IS MODULATION OF PAIN?
1,2
1,3
1
4
1,2
T.R. Stanton , H. Gilpin , E. Reid , C. Spence , G.L. Moseley
1
2
The University of South Australia, Adelaide, SA, Neuroscience Research Australia, Randwick, NSW,
3
4
Australia, The University of Nottingham, Nottingham, Department of Experimental Psychology,
University of Oxford, London, UK
Background and aims: Attention and expectation are well-known modulators of our nociceptive
system. We aimed to determine how spatially discrete modulation of pain is by investigating whether
pain is decreased when you expect to receive a painful stimulus on either side, that is, when
expectation/attention are spatially divided.
Methods: Noxious laser stimuli (Nd:YAP,1034µm) were applied in a randomised order to the dorsal
aspect of healthy volunteers' forearms under two conditions: Localisation (participants indicate which
zone, proximal or distal, was stimulated and provide pain scores) and No-localisation (provide pain
scores). Stimuli were also delivered to a middle zone (participants unaware) in both conditions. This
experiment was performed near the wrist (Experiment 1; 18 participants) and near the elbow
(Experiment 2; 16 participants).
Results: Mean pain ratings were significantly reduced in only the middle zone (and not in proximal or
distal zones), during Localisation vs. No-localisation (20.0 vs. 17.1) when stimuli were applied close to
the elbow. When stimuli were applied close to the wrist, pain was significantly reduced only in the
distal zone during Localisation (vs. No-localisation; 18.1 vs. 15.1). A third experiment, identical to
Experiment 1, but with addition of a fourth zone even closer to the wrist, confirmed the importance of
joint proximity finding significant reductions in pain scores during Localisation only in the most distal
zone (p=0.046).
Conclusions: These results suggest that spatially discrete modulation of nociception occurs,
although that proximity to a functionally relevant joint influences the effect. Possible mechanisms
include descending modulation and attention-related cortical mechanisms.
837
MECHANICAL PAIN MODULATION IN RESPONSE TO NOXIOUS CONDITIONING HEAT
STIMULUS IN CHRONIC LATERAL EPICONDYLALGIA: A CASE CONTROL STUDY
1,2
3
E. Lim , M. Sterling , B. Vicenzino
1
1
2
Physiotherapy, University of Queensland, Brisbane, QLD, Australia, Department of Physiotherapy,
3
Singapore General Hospital, Singapore, Singapore, Centre of National Research on Disability and
Rehabilitation Medicine, University of Queensland, Brisbane, QLD, Australia
Background and aims: Attenuation of pain from a noxious conditioning stimulus at a distinct site,
known as conditioned pain modulation (CPM), has been implicated in clinical pain states. Chronic
lateral epicondylalgia (LE), which is characterized by widespread mechanical hyperalgesia and spinal
cord hyperexcitability, is a clinical pain state that might plausibly involve a less efficacious CPM. The
aims were to determine if CPM occurs in LE and if it influenced by the site of the noxious conditioning
stimulation.
Methods: 41 LE and 44 healthy control participants indicated their pressure pain threshold (PPT)
over the lateral epicondyle(s) while experiencing a conditioning noxious heat stimulus at a forearm or
calf site. CPM was expressed as the difference in PPT before and during the conditioning stimulus.
Results: Conditioning Site (Calf v Forearm) by Group (LE v Control) and Conditioning Site by Side
(Affected v Unaffected; matched on dominance in Controls) interactions (p=0.036 and 0.048
respectively) were found on analysis of covariance (covariates: age, sex). Follow up tests of the
Group by Conditioning Site interaction showed a greater CPM score in Control compared to LE (89.6
kPa (95% confidence interval: 40.3 to 138.894)) when the calf was the heat pain-conditioning site.
This did not occur with the conditioning site at the forearm (P = 0.371).
Conclusions: The results suggest LE has a deficiency in the endogenous pain inhibition system. This
deficit in endogenous pain modulation might contribute to the mechanical hyperalgesia and spinal
cord hyperexcitability seen in LE.
838
ORAL ADMINISTRATION OF 2-HYDROXYOLEIC ACID INHIBITS REFLEX HYPERSENSITIVITY
AND OPEN FIELD-INDUCED ANXIETY AFTER SPARED NERVE INJURY IN THE RAT
G. Avila Martín, I. Galán Arriero, A. Ferrer Donato, J. Taylor
Sensorymotor Function Group, Hospital Nacional de Paraplejicos, Toledo, Spain
Background: The role of fatty acids in the modulation of change in sensory function in models of
neuropathic pain is unknown. In this study the antinociceptive effect of the omega 9 fatty acid 2hydroxyoleic acid was assessed on reflex sensitivity to mechanical and thermal stimuli, and in the
modulation of cerebrally-mediated behavioural responses measured with the place escape aversion
paradigm (PEAP) and open-field induced anxiety, up to 22 days after spared nerve injury (SNI).
Methods: Oral 2-Hydroxyoleic acid (400 mg/kg p.o.) was administered daily to 42 rodents (Wistar)
following SNI. OX-42 immunohistochemistry was performed to identify microglia modulation with 2hydroxyoleic acid treatment. Experimental groups included vehicle-treated sham operated animals
and Pregabalin (30 mg/kg p.o.) administered as a positive control.
Results: 2-hydroxyoleic acid significantly reduced microglia activation within the lumbar spinal dorsal
horn ipsilateral to the SNI, in addition to mechanical and thermal hypersensitivity, evident from 2 to 4
hours after administration. Furthermore 2-hydroxyoleic acid restored inner zone exploration of the
open field to the control level.
Conclusions: The omega 9 fatty acid modify, 2-hydroxyoleic acid, is antinociceptive following
peripheral nerve injury in the SNI model and prevents the development of open-field induced anxiety.
Acknowledgements: Study supported by the following research projects: Fundación Mutua
Madrileña 2010, INNPACTO IPT-010000-2010-016 from the Ministerio de Ciencia e Innovación. We
gratefully acknowledge LIPOPHARMA THERAPEUTICS, S.L. for 2-Hydroxy oleic acid.
839
MENTAL HEALTH AS A PREDICTOR FOR PATIENT-REPORTED OUTCOME AFTER A TOTAL
HIP ARTHROPLASTY - A COHORT STUDY OF 258 PATIENTS
1
2
1
R. Bilberg , B. Noergaard , K.K. Roessler , S. Overgaard
1
3
2
Institute for Psychology, University of Southern Denmark, Odense, Emergency Department, Koldin
3
Hospital, a part of Lillebael Hospital, Kolding, Department of Orthopaedics and Traumatology,
Odense University Hospital, Odense, Denmark
Background: Total hip arthroplasty (THA) is often very successful in alleviating hip pain, but a
minority of the patients has less favorable outcomes. The aim of this study is to investigate whether
patients' preoperative mental health is a predictor for the patient-reported outcome (PRO) after THA.
Method: Our prospective cohort study included 258 patients over a 14-months period, with two followups. The patients completed Common Mental Disorders - Screening Questionnaire (CMD-SQ),
Oxford Hip Score (OHS) and EuroQol 5 Dimension test (EQ-5D) before surgery and at 12 and 52
weeks after. Data on age, gender, Body Mass Index (BMI), co-morbidity, civil status, education level
and operation type were collected and analyzed by test-retest (Wilcoxon's rank test), logistic
regression and correlation analysis (Spearman's rho).
Results: Significantly improved outcomes about pain and mental health between baseline and
postoperative tests were reported. No correlation between patients' preoperative mental health and
PROs was found after adjustment for age and gender. Neither were baseline values as BMI, comorbidity, civil status, education level nor operation type found to affect mental health and OHS
outcomes.
Conclusion: Our research identified no correlation between patients' preoperative mental health and
PRO.
840
ROLE OF PERSISTENT INFLAMMATORY HYPERALGESIA IN THE DEVELOPMENT OF
DEPRESSION-LIKE BEHAVIOR IN RATS
L.C. Camargo, E.V. Dias, C.R. Sartori, C.A. Parada, C.H. Tambeli
Department of Structural and Functional Biology, Institute of Biology - University of Campinas,
Campinas, Brazil
Background and aim: Epidemiological studies have shown an association between depression and
chronic pain. Neural structures, neuronal circuitry and neurotransmission appear to be similarly
altered in chronic pain and depression, justifying the co-morbidity and several clinical peculiarities
shared in these situations. The physiological mechanisms underlying the relationship between chronic
pain and depression are not entirely elucidated. In this context, the aim of the present study was to
investigate whether persistent inflammatory hyperalgesia induces depression-like behavior in rats.
Methods: The persistent hyperalgesia was induced by daily injection of PGE 2 during 14 days
(100ng/50µl subcutaneous) in the hindpaw of male Wistar rats. Behavioral tests to evaluate the
mechanical hyperalgesia (Randall-Selitto) and the depressive-like behavior (sucrose preference) were
performed on days 0, 7 and 14. On days 7 and 14 after the interruption of the PGE2 injection, the
behavioral tests were repeated. All procedures were approved by Ethics Committee for Animal
Research at the Unicamp (protocol 2779-1).
Results: Persistent hyperalgesia, after 14 days of PGE2 injection, was confirmed by the significant
decrease in the nociceptive threshold of the group PGE2 (Figure 1), but no difference was observed in
the consumption of sucrose solution between the groups (Figure 2), which indicates the depressionlike behavior.
[Figura 1: Threshold nociceptive]
[Figura 2: Sucrose preference test]
Conclusions: Our data suggest that the PGE2-induced persistent hyperalgesia does not lead a
depressive-like behavior in rats when assessed by sucrose preference test.
Financial support: Fapesp.
841
EFFECTS OF NEFOPAM ON THE NEUROPATHIC PAIN IN STREPTOZOTOCIN-INDUCED
DIABETIC RATS
S.-S. Choi, Y.-G. Kong, J.-W. Shin, J.-H. Suh, J.-K. Leem
Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College
of Medicine, Seoul, Republic of Korea
Aims: The effect of nefopam on the diabetic neuropathic pain is unclear. Therefore, we investigated
the effect of nefopam on the diabetic neuropathic pain induced by streptozotocin in rats.
Methods: To determine if systemic administration of nefopam was involved in the streptozotocininduced diabetic neuropathic pain, pretreatment with nefopam (30 mg/kg) was performed i.p. for 30
min prior to streptozotocin (60 mg/kg) treatment. Mechanical and cold allodynia were tested before,
and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated in hot-plate
test.
Results: The withdrawal threshold to mechanical stimuli was reduced significantly after streptozotocin
treatment in a time dependent manner. The withdrawal response to cold stimuli was significantly
decreased in streptozotocin treated rats. In addition, streptozotocin treatment decreased the pawwithdrawal latencies in hot plate test. Pretreatment with nefopam significantly inhibited the
streptozotocin-induced mechanical and cold allodynia, but not thermal hyperalgesia.
Conclusions: These results demonstrate that nefopam has strong anti-allodynic effects on the
streptozotocin-induced diabetic rats.
842
DIFFERENTIAL CONTRIBUTION OF COLLATERAL REINNERVATION AND NERVE
REGENERATION TO NEUROPATHIC PAIN
S. Cobianchi, J.P. de Cruz, X. Navarro, Group of Neuroplasticity and Regeneration
Institute of Neuroscience, Universitat Autonoma de Barcelona, and CIBERNED, Barcelona, Spain
Peripheral nerve injuries induce plastic changes on primary afferents fibers affecting not only
damaged axons but also intact axons in nearby territories, contributing to neuropathic pain. Sciatic
nerve injury models are commonly used to assess changes in pain threshold and recovery of
nociception, often disregarding the pattern of skin innervation and thus leading to misinterpretation of
nerve regeneration. We present a standardized study of adjacent hyperalgesia mediated by intact
saphenous nerve, and recovery of sciatic sensory function.
After sciatic nerve section and suture repair, we mapped nociceptive reinnervation of the plantar skin,
and assessed mechanical and thermal pain thresholds in saphenous and sciatic test sites. Pain
testing was made during one month, before and after transection of the saphenous nerve at 2 and 4
weeks. Skin innervation was analyzed at the same test sites by immunohistochemistry.
Sciatic injury initially divided the rat paw into a sensitive and an insensitive area. Nociceptive fibers of
the saphenous nerve rapidly spread to the denervated sciatic territory and paralleled development of
mechanical allodynia and thermal hyperalgesia. After return of sensation mediated by the regenerated
sciatic nerve at 3 weeks, mechanical hyperalgesia developed also in its territory. Elimination of
saphenous nerve demonstrated that it mediates neuropathic pain before and after sciatic
regeneration. Analysis of sensory fibers revealed early reinnervation of overlapping skin territory, and
after sciatic regeneration nociceptors hyperreinnervated the epidermis.
In conclusion, after sciatic nerve injury collateral sprouting and nerve regeneration differently
contribute to sensory reinnervation and neuropathic pain.
843
INVOLVEMENT OF PRELIMBIC PREFRONTAL MEDIAL CORTEX ON THE NEUROPATHIC PAIN
INDUCED BY SCHIATIC NERVE CHRONIC CONSTRICTION INJURY
1
2
3
P. de Medeiros , R.L. de Freitas , S.H. Ferreira , N.C. Coimbra
1
1
Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology and
2
Department of Neurocience and Behavioural Sciences, Laboratory of Neuroanatomy and
3
Neuropsychobiology, Department of Pharmacology, Department of Pharmacology, Medicine School
of University of São Paulo, Ribeirão Preto, Brazil
The prelimbic division (PL) of medial prefrontal cortex (MPFC) is important for the perception of acute
and chronic pain. The aim of the present work was to investigate the involvement of the PL cortex in
the maintenance of the neuropathic pain induced by chronic constriction injury of the schiatic nerve
(CCI). Male Wistar rats (n=6-7 per group) were used. Neuropathic pain was induced by CCI and the
control group was submitted to sham surgery (without CCI). After 2 or 14 days of CCI or sham
procedure, a guide cannula was unilaterally implanted into the PL cortex through of stereotaxic
surgery. The withdrawal latency to mechanical stimulation was recorded using von Frey's tests 7, 14,
21 and 28 days after CCI. Furthermore, PL cortex-treatment with the synaptic blocker cobalt chloride
(1.0 mM/ 200 nL) or saline (NaCl 0.9%; 200nL) was performed 7, 14, 21, or 28 days after CCI or
sham procedure, followed by von Frey´s test stimulation during 60 minutes.The present data showed
that PL cortex-pretreatment with cobalt chloride did not increase the mechanical threshold in the von
Frey test after 7 and 14 days of CCI (P>0.05, in all the cases). However, cobalt chloride microinjected
into the PL cortex increased the nociceptive threshold after 21 and 28 days of neuropathic pain
induced by CCI (P< 0.05). These findings suggest that the PL division of the MPFC is involved in the
potentiation and maintenance of the chronic pain in the model of neuropathic pain in rodents.
844
SPONTANEOUS BURROWING, AN OUTCOME MEASURE OF GLOBAL WELLBEING, IN
CONTRAST TO MECHANICAL HYPERSENSITIVITY IS NOT SUBJECT TO EXPERIMENTERINDUCED VARIABILITY
A. Delaney, C.I. Svensson
Dept. of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden
Background and aims: Outcome measures used in pain research to assess injury-induced pain-like
behaviours in preclinical models are often dependent on the assessment of withdrawal reflexes,
typically evoked by mechanical or thermal stimuli. Advances in predictive validity may be improved by
assessing the global impact of pain and the reinstatement of innate behaviours suppressed by injury.
Burrowing, an indicator of the global “wellbeing” of the animal can be objectively measured. Observer
variability of pain-like behaviours is dependent on various factors, with one of the key factors being
the experimenter. We aimed to assess the impact of several environmental factors on burrowing
behaviour in naive mice.
Methods: Spontaneous burrowing behaviour in naive C57/Black6J mice was assessed to determine
the impact of the following environmental factors; test length (30 minutes, 1 or 2 hours); light levels
(50 or 90 lux); in addition to time of testing during the light cycle. To determine the effect of
experimenter-induced variability, male and female experimenters assessed burrowing behaviour and
mechanical hypersensitivity using von Frey filaments in the same animals.
Results: We show mechanical hypersensitivity is affected by the experimenter; with male
experimenters observing higher thresholds than female experimenters. Burrowing behaviour was
unaffected by the sex of the experimenter, but was affected by the length of the test.
Conclusions: Burrowing, which can be utilised as an outcome measure of the global impact of
wellbeing is not subject to experimenter-induced variability when compared to mechanical
hypersensitivity.
845
THE P38Α MAPK INHIBITOR UR13870 MODULATES SPINAL NOCICEPTIVE REFLEX AND
CEREBRALLY MEDIATED BEHAVIORS IN NEUROPATHIC PAIN MODELS IN THE RAT
I. Galan Arriero, G. Avila Martin, A. Ferrer Donato, S. Albu, J. Gomez Soriano, C. Simon, J. Taylor
Sensorimotor Function Group, Hospital Nacional de Parapléjicos, Toledo, Spain
Background: Microglial cells play an important role in the development and maintenance of
neuropathic pain following peripheral and central injuries of the nervous system. In this study, we
tested a novel inhibitor of p38α MAPK, UR13870, for its therapeutic efficacy to alleviate spinal
nociceptive reflex hypersensitivity and cerebrally mediated behavioural responses that develop in the
Spared Nerve Injury model (SNI) and contusion Spinal Cord Injury model (SCI) in rats.
Methods: Forty eight male SpragueDawley rats were divided into six groups:
i) Sham-SNI+Vehicle p.o.,
ii) SNI+Vehicle p.o.,
iii) SNI+UR13870 10mg/kg p.o.,
iv) Sham-SCI+Vehicle i.v.,
v) SCI+Vehicle i.v. and
vi) SCI+UR13870 1mg/kg i.v.
Animals were tested for mechanical and cold hyperreflexia. Place escape/avoidance paradigm
(PEAP) and Open Field-Anxiety tests were performed to document cerebrally-mediated behavioural
responses.
Results: Treatment with UR13870 inhibited microglia activation following SNI at 7 days, and reduced
von Frey-evoked reflex hypersensitivity with open-field induced anxiety at 22 days after injury. In the
SCI model, although no nociceptive reflex modulation was observed above or below the injury level
with the Randal-Sellito test, a reduction in PEAP avoidance behavior was demonstrated at 42 days
post injury.
Conclusions: The p38α inhibitor UR13870 is effective as an antinociceptive agent and prevents
anxiety in the SNI model, while controlling the affective component of SCI.
Acknowledgements: UR13870 was donated by PalauPharma, S.A. (Barcelona, Spain), and is
currently within clinical development.
846
EFFECT OF S (+) KETAMINE ON THE CYCLOOXYGENASE-2 (COX-2) EXPRESSION IN A
EXPERIMENTAL MODEL OF OSTEOARTHRITIS
L.M. Leite, J.B.S. Garcia, E.D.S. Neto, P.P.D.A. Pedro, M.D.S.D.S. Cartagen
Medicine, Federal University of Maranhão - UFMA, São Luís, Brazil
Background and aims: The mechanism of action of S (+)-ketamine after intraarticular injections is
not fully understood. Our objective was to investigate the peripheral effect of S(+) ketamine on the
cyclooxygenase-2 (COX-2) expression in a model of osteoarthritis in animals.
Methods: Seventy-two rats were divided in three groups (n=24). In one group only intra-articular
injections of saline were administered into the both knee joints and in two groups intra-articular
injections of Monosodium Iodoacetate (MIA) and saline were administered to rats into the right and
left knee joints, respectively. Seven days after the injection of MIA, the two groups receive a single
intra-articular application of Saline or Ketamine S (+) (0.5 mg/Kg). On days 7, 14, 21 and 28 the
animals were anesthetized and sacrificed, and the synovial membrane was extracted and submitted
to immunohistochemistry analysis of the cyclooxygenase-2. Throughout the study, there were 29
losses of materials that were to be analyzed, totaling n = 43. The protocol used for the
immunohistochemical interpretation was cytoplasmic immunostaining of COX-2 in cells of the synovial
membrane, conjunctive and adipose tissue, according to the intensity of the stain.
Results: COX-2 reactivity was positive in 53.8% of animals in the group without OA, in 60% of those
of the OA group with saline, and in 80% of group OA with ketamine, with no statistically significant
difference between the groups (p = 0.3069).
Conclusions: The study implies that intra-articular injections of S(+) ketamine did not inhibit the
COX-2 expression in osteoarthritis models in rats.
847
CHANGES IN THE DORSAL ROOT GANGLIA OF HORSES SUFFERING FROM SEVERE FOOT
PAIN
1
2
3
2
2
F.C. Gauff , H. Jerina , E. Jones , R. Mitchell , S. Fleetwood-Walker , T. Licka
4
1
Department of Horses and Small Animals, University of Veterinary Medicine, Vienna, Vienna,
2
3
Austria, Centre for Integrative Physiology, Sensory Neuroscience, Royal (Dick) School of Veterinary
4
Studies, University of Edinburgh, Edinburgh, UK, Department of Horses and Small Animals,
Veterinary University Vienna, Vienna, Austria
Equine laminitis is associated with signs of severe pain in the foot. The underlying basis is poorly
understood. Hyperinsulinaemia is a common clinical precursor for laminitis, and in this situation
increased concentrations of Endothelin 1 (ET-1) in nerve fibres have been documented in the foot.
The aim of this study was to identify how the dorsal root ganglia may contribute to ET-1 associated
nociceptive signalling in laminitis and compare it to ET-1 receptors (ETR) in foot tissue.
Dorsal root ganglia (DRG) from cervical segment eight (forelimb innervation) were obtained postmortem from five severely painful laminitic horses and four control horses. Additionally,
immunohistochemical changes in ETR A and B in foot tissue were assessed after hyperinsulinaemia
(5 limbs) and in controls (10 limbs).
Expression of ET-1 and ETRA but not ETRB was increased in peripherin-positive cells of DRGs in
laminitic horses. After hyperinsulinaemia, ETRA and ETRB stained more in the endothelium of
vessels in the foot, while ETRA in axons decreased.
Increased expression of ET-1 in DRGs and in peripheral nerves of affected tissue may relate to the
severity of laminitic pain. Increased expression of ETRA in the DRG potentially increases nociception
from increased ET-1 in the foot, as shown after intraplantar ET-1 injections in rodents. Horses
suffering from laminitis as a consequence of hyperinsulinaemia may be a naturally occurring model of
severe, chronic pain, potentially suitable for research into the underlying pain biology as well as for
testing new analgesic interventions.
(Authors Gauff & Jerina contributed equally to this work.)
848
HYPERALGESIC PRIMING IN THE KNEE JOINT: THE INFLUENCE ON DISTAL PAIN
RESPONSES
1
1
2
A. Haywood , V. Chapman , G. Hathway
1
2
Arthritis Research UK National Pain Centre, School of Life Sciences, School of Life Sciences,
University of Nottingham, Nottingham, UK
Background and aims: The aim of this study was to investigate sensitization mechanisms in the
knee joint and their influence on pain responses from sites distal to the joint. Here we describe
hyperalgesic priming of the knee joint following repeated injection of prostaglandin E2 (PGE2) and the
impact of this sensitization on changes in hind-paw pain thresholds.
Methods: All adult male Sprague-Dawley rats (250-300g) received intra-articular (i.a.) saline (35ul) on
day one and then i.a. injection of PGE2 (5ug/35ul) on day two. On day four, rats received a second
i.a. injection of PGE2 (5ug/35ul) co-administered with either vehicle or lidocaine (1mg). Weight
bearing asymmetry and mechanical hind-paw withdrawal thresholds (PWT) were assessed at
baseline and at 30, 60 and 120mins post-interventions. Statistical analysis: two way ANOVA with
Bonferroni, n=8 rats per group.
Results: The first intra-articular injection of PGE2 produced significant weight bearing asymmetry,
compared to vehicle (Figure 1), but no change in PWT. The second intra-articular injection of PGE2
two days later produced a significantly bigger shift in weight bearing asymmetry, compared to the first
PGE2 injection, and a significant (P< 0.05) decrease in PWT. Lidocaine abolished the PGE2 induced
weight bearing asymmetry and changes in PWT.
[Figure 1]
Conclusions: Repeated knee joint injection of PGE2 produces hyperalgesic priming and decreased
hind-paw withdrawal thresholds, suggesting that this priming is associated with changes in the central
processing of sensory inputs.
849
CD200R1 AGONIST ATTENUATES INFLAMMATORY REACTIONS IN A RAT MODEL OF
NEUROPATHIC PAIN
1
2
2
M. Hernangómez , P. Dubový , I. Svíženská , I. Klusáková
1
2
2
Central European Institute of Technology (CEITEC), Masaryk University, Central European Institute
of Technology (CEITEC), Department of Anatomy, Division of Neuroanatomy, Medical Faculty,
Masaryk University, Brno, Czech Republic
Background and aim: The existence of CD200 in glial cells and neurons of the central nervous
system is well-known, but there is limited information on the distribution of CD200 and CD200R in the
peripheral nervous system. Here, we investigate bilateral changes of CD200 and CD200R expression
in L4-L5 dorsal root ganglia (DRG) after chronic constriction injury (CCI) of the sciatic nerve and
evaluate the efficacy of CD200Fc (CD200R1 agonist) in CCI neuropathic pain model.
Method: Rats undergoing unilateral CCI were left to survive for 3, 7 or 14 days. In parallel, after 7
days CCI rats were treated with CD200Fc. Neuropathic pain induction was tested by measurement of
mechanoallodynia and thermal hyperalgesia. After the survival time, L4-L5 DRG and spinal cord were
removed from naive, operated, sham-operated and control (CCI+saline) rats and CD200, CD200R, IL1beta and OX-42 proteins were detected by immunohistochemical staining.
Results: Unilateral CCI induced a transient bilateral increase of CD200 and CD200R protein levels in
satellite glial cells after 3, 7 and 14 days from operation. Furthermore, CD200Fc treatment is able to
reduce the microglia activation in spinal cord and IL-1beta expression in DRG after 7 days from CCI
operation compared with CCI+saline animals.
Conclusion: Our results suggest that CD200/CD200R might play an inhibitory role of
neuroinflammatory reactions in the DRG and spinal cord to keep homeostasis after neuropathic
stress.
This work was supported by the project CEITEC (CZ.1.05/1.1.00/02.0068) from European Regional
Development Fund, InterBioNet (CZ.1.07/2.4.00/17.0042) and CZ.1.07/2.3.00/30.0009.
850
THE ANALGESIC ACTION OF P2Y12 RECEPTOR ANTAGONISTS IN ANIMAL MODELS OF
INFLAMMATORY AND NEUROPATHIC PAIN
G. Horvath, B. Sperlágh
Institute of Experimental Medicine Hungarian Academy of Sciences, Budapest, Hungary
Background and aims: P2Y12 receptor (P2Y12R) belongs to metabotropic purine receptors and is the
molecular target of widely used antithrombotic drugs, such as clopidogrel (Plavix). Our aim was to
assess the effects of P2Y12R antagonists in rodent models of inflammatory, neuropathic pain and on
acute thermal nociception.
Methods: To examine neuropathic pain behavior we ligated the nervus ischiadicus partially (Seltzer
model) and mechanical allodynia/hyperalgesia was measured by dynamic plantar aesthesiometer
(von Frey method) 7 days later in rats. In the inflammatory pain model Complete Freund adjuvant
(CFA) was injected into the right hindpaw and mechanical allodynia was tested 48h after the injection.
The hot-plate test was applied to investigate acute thermal nociception. In addition to clinically used
P2Y12 blockers, the effect of the potent and selective P2Y12 receptor antagonist PSB-0739 and
P2Y12R knockout (P2Y12R-/-) mice were also examined.
Results: All the tested P2Y12R antagonists had analgesic action in inflammatory pain with the
following rank order of potency (mED): PSB-0739 i.t. = cangrelor > reactive blue 2 > MRS2395 >
ticlopidine =clopidogrel. Similar findings were obtained in the neuropathic pain model: PSB-0739 i.t. =
cangrelor > MRS2395 > clopidogrel > ticlopidine.
P2Y12R-/- mice showed significant attenuation of mechanical hyperalgesia following CFA injection,
when compared to wild-type mice.
In the hot plate test the following rank order potency was obtained: PSB-0739 i.t.> MRS2395>
clopidogrel > ticlopidine, whereas reactive blue 2 and cangrelor was ineffective.
Conclusions: Our data suggest that P2Y12R can be a potential target for treating neuropathic and
inflammatory pain.
851
BEHAVIOR OF IBA1-IMMUNOREACTIVE CELLS IN THE TRIGEMINAL GANGLION OF THE RAT
WITH MENTAL NERVE LIGATION
1,2
1,2
2
1
K. Kadono , A. Kawano , H. Niwa , S. Honma , S. Wakisaka
1
1
2
Department of Oral Anatomy and Developmental Biology, Graduate School of Dentistry, Department
of Dental Anesthesiology, Graduate School of Dentistry, Osaka University, Suita, Japan
Background: Many studies focused on the role of microglia at the stage of neuropathic pain using
ionized calcium binding adaptor molecule 1 (Iba1) as a marker, and found that microglia releases
various cytokines, and are activated at the neuropathic stage caused by peripheral nerve injury. Little
is known, however, on the expression of Iba1 in the sensory ganglion following nerve injury. Thus, we
examined the behavior of Iba1-immunoreactive (IR) cells in the trigeminal ganglion following mental
nerve ligation (MNL).
Methods: Unilateral MNL was applied to the rat, and mechanical threshold was examined using von
Frey´s method. Expression of Iba1 in the trigeminal ganglion was examined by
immunohistochemistry.
Results: Mechanical threshold significantly decreased bilaterally following MNL. On the ipsilateral
side, mechanical hyperalgesia persisted up to 4 weeks following MNL, while it recovered 3 weeks
after MNL on the contralateral side. In normal trigeminal ganglion, Iba1-IR cells were round to oval
cells in shape and located between neurons. They co-expressed ED1, a marker for phagocyte.
Following MNL, Iba1-IR cells increased in number more apparently on the ipsilateral side, and they
extended spine near the trigeminal neurons.
Conclusion: The present study clearly demonstrated that Iba1 is expressed in phagocytotic cells in
the trigeminal ganglion, and extended spines toward trigeminal neurons following MNL that caused
mechanical hyperalgesia. Those findings suggest that Iba1-IR phagocytotic cells may contribute to
the stage of mechanical hyperalgesia caused by peripheral nerve injury.
852
ROLE OF SCHWANN CELL AUTOPHAGY IN AN ANIMAL MODEL OF NEUROPATHIC PAIN:
FUNCTIONAL AND STRUCTURAL INVESTIGATIONS
1,2
2
3
4
2,5
2,6
1,2
2,6
S. Marinelli , F. Nazio , A. Tinari , L. Ciarlo , M. D'Amelio , L. Pieroni , V. Vacca , A. Urbani ,
2,7
4,8,9
1,2
F. Cecconi , W. Malorni , F. Pavone
1
2
CNR - National Research Council, Cell Biology and Neurobiology Institute, IRCCS Fondazione
3
4
Santa Lucia, Dept of Technology and Health, Dept of Therapeutic Research and Medicine
5
Evaluation, Section of Cell Aging and Degeneration, Istituto Superiore di Sanità, Medical School,
6
University Campus-Biomedico, Dept of Experimental Medicine and Surgery, Division of Biochemistry,
7
8
Dulbecco Telethon Institute, Dept of Biology, Tor Vergata University of Rome, Rome, San Raffaele
9
Institute, Sulmona, Center of Integrated Metabolomics, Rome, Italy
Background and aims: Schwann cells (SCs) have a fundamental role in Wallerian degeneration, one
of the most elementary reaction of the peripheral nervous system that occurs when nerve fibre is
damaged. Immediately after injury, SCs activate the autophagic process and remove myelin debris
from the nerve. This physiological cytoprotective mechanism allows nerve regeneration. Neuropathic
pain (NeP), a chronic neurological disease, is concomitant to nerve lesion and can persist beyond
nerve regeneration. The role of SC autophagy in NeP mechanisms is still unknown.
Methods: Chronic constriction injury mouse model of NeP was used to in vivo investigate:
1) the pharmacological activation or inhibition (by rapamycin or 3-Methyladenine, respectively) of SCs
autophagy on long-term pain-associated behaviour in CD1 mice and
2) the behavioural response of Ambra1+/- transgenic mice, defective for the gene Ambra1 involved in
autophagy activation.
Behavioral responses, immunohistochemical analyses, electron microscopy for ultrastructural
evaluations and proteomic analysis for protein expression following pharmacological treatments were
used.
Results: Stimulation of SCs autophagy in the first week after lesion counteracts NeP. As a matter of
fact, a local administration of rapamycin induces analgesic and anti-inflammatory effects, blocks pain
chronicization and promotes nerve regeneration. On the contrary, the genetically or
pharmacologically-induced decrease of SCs autophagy leads to NeP maintenance.
Conclusions: These results demonstrate that a defect of SCs autophagy, an early peripheral nervous
mechanism, may be at the origin of long-term-pain processes.In a clinical perspective this study
suggests that an immediate intervention is desirable for preventing NeP chronicization.
853
CARRAGEENAN INDUCED INFLAMMATORY PAIN, IS IT A GOOD ANIMAL MODEL TO STUDY
CHRONIC MUSCLE PAIN?
M.I. Martín, A. Bagüés, E.M. Sánchez
Pharmacology and Nutrition, Health Sciences Faculty, Rey Juan Carlos University, Madrid, Spain
Background and aims: Chronic musculoskeletal pain is a major clinical problem, though few models
have been developed to study this pain. Previously, we have found differences in opioid and
cannabinoid pain modulation between the trigeminal and spinal systems in acute muscle pain animal
models.
Carrageenan has been extensively used to study inflammatory pain, though, when using it to study
muscle pain there is few and contradicting data.
Our aim is to evaluate acute/chronic nociception induced by carrageenan in masseter (trigeminal
territory) and gastrocnemius (spinal innervation) which will permit future comparisons of pain
modulation in both systems.
Methods: We have studied the nociceptive effect of 3mg of carrageenan injected in the masseter and
gastrocnemius muscles of male rats. All carrageenan injections were performed under isoflurane
anaesthesia. To assay this nociceptive effect, we evaluated the von Frey filaments for mechanical
allodynia, PAM (pressure application measurement) device for mechanical hyperalgesia, and
hypertonic saline injection for chemical hyperalgesia. These tests were performed at different time
points: baseline, 4, 24, 48 hours and 7 days after carrageenan injection.
Results: Under our experimental conditions carrageenan failed to induce muscle nociception in both
muscles in all the tests performed, though it tended to induce mechanical hyperalgesia in the
gastrocnemius.
Conclusions: Taking into account our results and previous data, carrageenan, at the tested dose,
does not seem to be a reliable model to study chronic muscle pain. Future studies are needed with
higher concentrations of carrageenan or using chemicals that potentiate the inflammatory response.
Supported by: SAF2009-12422-CO2-01, SAF2012-40075-C02-01
854
ANTIALLODYNIC EFFECTS OF INTRATHECAL ADMINISTRATION OF ATYPICAL
ANTIPSYCHOTICS IN RAT MODEL WITH OROFACIAL NEUROPATHIC PAIN
1
2
3
2
K. Nakai , A. Nakae , R. Hashimoto , Y. Fujino , K. Hosokawa
1
4
2
Department of Plastic and Reconstructive Surgery, Sakai City Hospital, Sakai, Department of
Anesthesiology & Intensive Care Medicine, Osaka University Graduate School of Medicine,
3
Molecular Research Center for Children's Mental Development, United Graduate School of Child
4
Development, Department of Plastic Surgery, Osaka University Graduate School of Medicine, Suita,
Japan
Background and aims: The atypical antipsychotics are drugs that have been widely used for the
treatment of psychiatric conditions, such as schizophrenia, acute mania, bipolar depression, and
psychotic agitation. They have high affinity to both dopamine and serotonin receptors. The central
dopaminergic and serotoninergic systems are involved in modulation of nociception at spinal level.
Even though, there is still limited evidence for the effect of atypical antipsychotics on orofacial
neuropathic pain. Chronic constriction injury to the infraorbital nerve (ION-CCI) has been proven to be
a useful model for orofacial neuropathic pain. This study evaluated the potential antiallodynic effects
of intrathecally atypical antipsychotic drugs administration in ION-CCI rat model.
Methods: Male Sprague Dawley rats underwent unilateral CCI to the right ION. Two nylon (5-0)
ligatures were tied around the ION. Series of von Frey filaments were used to determine pain
hypersensitivity to mechanical stimulation on day 14 after surgery.
A polyethylene (PE-10) catheter was implanted for upper cervical spinal drugs injection. The rats were
allowed to recover for 5 days. The time course of antiallodynic effects and the dose-response effects
of intrathecally administered four atypical antipsychotics; aripiprazole, quetiapine, olanzapine, and
risperidone, were evaluated. The time course data for the dose-response effects were analyzed by
two-way analysis of variance and Tukey-Kramer multiple-comparison test.
Results: Intrathecal administration of aripiprazole, quetiapine, olanzapine, and risperidone increased
mechanical thresholds in a dose dependent manner (P < 0.05).
Conclusions: The results indicated that atypical antipsychotics may elicit antiallodynic effects in rat
orofacial neuropathic pain model.
855
STRUCTURAL AND FUNCTIONAL SEX-RELATED DIFFERENCES IN NEUROPATHIC MICE: THE
RELEVANCE OF GLIAL CELLS
1,2
1,2
2,3
1,2
V. Vacca , S. Marinelli , L. Pieroni , S. Luvisetto , F. Pavone
1
1,2
2
CNR - National Research Council, Cell Biology and Neurobiology Institute, IRCCS Fondazione
3
Santa Lucia, Department of Experimental Medicine and Surgery, Division of Biochemistry University
of 'Tor Vergata', Roma, Italy
Background and aims: Recently the study of sex differences in pain received increased attention
even if the mechanisms underlying these differences, mainly as concerns neuropathic pain, are
complex and far from understood. It is increasingly recognized that glial cells are key players in the
development and maintenance of neuropathic pain and are affected by sex hormones. The aim of the
present study was to investigate how pain-related responses are differently modulated in male and
female neuropathic mice and how glia activation is critically involved.
Methods: Chronic Constriction Injury (CCI) of sciatic nerve was used as neuropathic pain model in
male and female CD1 mice. Behavioral responses and mechanical nociceptive threshold were tested.
Immunofluorescence staining of glial markers (GFAP: astrocytes; cd11b: microglia) at the spinal cord
level and of myelin-related proteins in sciatic nerve was performed. A proteomic analysis was also
carried out before and after CCI.
Results: Neuropathic pain and reactive gliosis induced by CCI disappeared in male mice, which
showed a complete recovery 81 days post surgery. In female mice both allodynia and gliosis were still
present 121 days after CCI. Faster nerve regeneration in males than in females was supported by the
expression of important proteins associated with nerve injury and repair.
Conclusions: The differences observed in the present research between males and females in the
evolution of neuropathic pain may ameliorate the comprehension of the mechanisms underlying this
chronic disease and significantly improve the development of more effective, more specific pain
therapies.
856
PHARMACOLOGICAL MODULATION OF INFLAMMATORY HYPERALGESIA IN
OSTEOPOROTIC FEMALE RATS
M. Ratkova, K. Surchev, A. Tsakova, S. Surcheva, M. Vlaskovska
Department of Pharmacology, Medical University of Sofia, Sofia, Bulgaria
Background: Osteoporosis is a slowly progressive disease characterized by low bone mass and
increased bone fragility, currently attributed to various endocrine, metabolic and mechanical
factors.Sufficient evidence suggests that pro-inflammatory cytokines have been implicated as primary
mediators of the accelerated bone loss at menopause.
Aim: The aim of our work was to study the development of inflammation in osteoporotic rats and to
determine the changes in analgesic activity of widely used NSAIDs by genistein.
Methods: The animal model of ovariectomy (OVX) was performed as commonly used in research on
postmenopausal osteoporosis. Six months after ovariectomy and 2 months after treatment with
genistein (2.5 mg/kg) inflammatory hyperalgesia was induced by intraplantar injection of 1%
carrageenan. Spontaneous pain was assessed with incapacitance analgesia meter. Hyperalgesia was
measured by paw pressure test and heat plantar test. Edema was determined using a
plethysmometer.Groups of control nonovariectomized (nonOVX), ovariectomized (OVX), OVX treated
with genistein 2.5 mg/kg s.c, every other day (8 rats each) were treated with metamizol (100 mg/kg),
ibuprofen (20 mg/kg). Results. Long term treatment of osteoporotic rats with genistein modulates the
carrageenan-induced edema, increases the antiexudative effect of metamizol and ibuprofen. Changes
in the weight-distribution ratio (incapacitance test) were significantly greater after carrageenaninduced hyperalgesia. Genistein alleviated painful behavior and increased analgesic activity of
metamizol in incapacitance test.
Conclusion: Our data demonstrate that long term treatment of osteoporotic rats with genistein
enhances the analgesic activity of some NSAIDs.
Acknowledgements: The research was supported by the Council of Medical Sciences of Medical
University Sofia (Grant 61/2012).
857
TRAMADOL REDUCES PAIN AND DEPRESSION IN AN ANIMAL MODEL OF NEUROPATHIC
PAIN
M.-C. Reitz, O. Caspani, R.-D. Treede
Chair of Neurophysiology, Medical Faculty Mannheim of the University of Heidelberg, Mannheim,
Germany
Background and aims: Depression is a common comorbidity of neuropathic pain. Tramadol is a
weak µ-opioid receptor agonist which also inhibits the re-uptake of norepinephrine and serotonin. In
this study we investigated the effects of Tramadol on pain as well as depression in a neuropathic pain
model in rats.
Methods: We used chronic constriction injury of the sciatic nerve (CCI) in rats as an animal model on
neuropathic pain. We then assessed mechanical sensitivity and depression-like-behaviors in sham
and CCI rats after saline and tramadol injection (10 mg/kg i.p.). Specifically, we used the electronic
von Frey test to measure mechanical sensitivity and the forced swimming test (FST) to record
depression-like-behaviors.
Results: In the electronic von Frey test rats with CCI showed an extensive decrease of the paw
withdrawal threshold (PWT) compared to sham. Tramadol injection substantially attenuated this
decrease.
During the FST rats with CCI showed longer immobility than sham. Tramadol reduced the immobility
time in the CCI rats while it had no effect on the sham rats.
Conclusions: Tramadol significantly reverses the changes in mechanical sensitivity as well as
depression-like-behaviors that are caused by nerve injury. A deeper investigation on the effects of
Tramadol on the serotonergic and noradrenergic system might reveal important information in the
treatment of depression related to neuropathic pain and help for better treatment.
Acknowledgement: This work was supported by the Europain Project from Innovative Medicines
Intitiative Joint Undertaking, including an unrestricted grant from Boehringer Ingelheim.
858
THE EFFECTIVE PIPERINE CONCENTRATION IN ANIMAL MODEL OF TEMPOROMANDIBULAR
JOINT PAIN
C.M. Rizzatti-Barbosa, A.P.V.B. Martins
Prosthesis and Periodontology, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil
Piperine is the main pungent black pepper and it activates the TRPV1 (Transient Receptor Potential
Vanilloid 1) of sensory neurons.
Objective: To determinate the minimum effective piperine concentration that stimulates sensory
neurons in animal model of temporomandibular joint (TMJ) pain.
Methods: Forty eight Wistar female rats were randomly divided in six groups (n=8), that received 30µl
injection in the right TMJ:
control group - ethyl alcohol, Tween 80, sterile saline;
-2
-2
-2
-2
-2
experimental groups: 1 x 10 µg/ml; 2 x 10 µg/ml; 3 x 10 µg/ml; 4 x 10 µg/ml or 5 x 10 µg/ml of
piperine diluted in the same solution used in the control group.
The animals were injected during the estrous hormonal cycle, and their nociceptive behaviors were
evaluated immediately after the injections in a custom-made cage (12x12x12 inches) with 4 mirrored
walls. The data were submitted to the ANOVA one-way test and Bonferroni´s test (post-hoc, α=0.05).
Results: The means (±SEM) for time (seconds) of control group and experimental groups of rubbing
were 33.37 (±5.74), 26.12 (±6.11), 100.37 (±30.42), 62.12 (±21.16), 51.12 (±10.81), and 100 (±27.82),
respectively; the head flinches data were 29.37 (±4.46), 38.87 (±7.07), 30.5 (±4.68), 44.87 (±4.76),
27.27 (±4.89), and 25 (±4.39), respectively; finally, the sum of both behavior were 61.87 (±2.98),
66.25 (±3.48), 130.87 (±27.53), 107 (±17.83), 78,87 (±11.04), and 125 (±27.55), respectively.
Conclusion: The results suggest the minimum effective concentration to promote pain in the TMJ is 2
-2
x 10 µg/ml, and also, this piperine concentration can be used in animal model of temporomandibular
joint (TMJ) pain.
859
TAPENTADOL HAS ANALGESIC EFFECT AND DECREASE EARLY PROINFLAMMATORY
CYTOKINES ON PACLITAXEL-INDUCED NEUROPATHY IN RATS
A. Rodríguez, D. Pascual, M.Á. García, E. Sánchez, M.I. Martín, C. Goicoechea
Farmacología y Nutrición, Universidad Rey Juan Carlos, Alcorcón, Spain
Background: Spinal cord glial cells are activated after nerve injury and contribute to the development
and maintenance of neuropathic pain. Paclitaxel, an antineoplastic drug, induces a painful peripheral
neuropathy as a common side-effect.
The aim of our study was to evaluate if tapentadol can reverse neuropathic symptoms (hyperalgesia
and allodynia) and to analyse the release of early proinflammatory cytokines in the spinal cord.
Methods: Painful neuropathy was induced in male Wistar rats (225-250g.) by intraperitoneal (i.p.)
administration of paclitaxel (1 mg/kg) on four alternated days (1, 3, 5 and 7). The plantar surface of
hindpaws was tested for heat-hyperalgesia and tactile-allodynia. Three groups of paclitaxel-treated
rats received tapentadol (2.5, 5 and 10 mg/kg, i.p.) or saline on day 28. On day 8, a quantitative
determination of spinal IL-1β, IL-6 and TNF-α level was performed by ELISA.
Results: Paclitaxel produced a statistically-significant mechanical-allodynia (decrease of mechanical
threshold on 21%). Tapentadol acute administration produced an antiallodynic effect at lower dose
(107%±5.7 vs 100% control) and an analgesic effect at doses of 5 and 10mg/kg (114%±6.5 and 125%
±6.8 vs 100% control).
Paclitaxel increased proinflammatory cytokines levels: 75% increased basal levels of TNF-alpha, and
50% of IL-6 and IL-1b levels. Tapentadol acute treatment, on day 8, returned cytokines levels to
control values.
Conclusions: These results indicate that tapentadol acute administration has analgesic effect and
blocks the release of early proinflammatory cytokines involved in the development of paclitaxel
neuropathic pain.
Acknowledgements: Carmen Merino and Iván Álvarez (for technical support). Supported by
Grünenthal Pharma.
860
ABNORMAL NEUROPATHIC PAIN IN THE CNS-SPECIFIC ERK2 KNOCKOUT MOUSE
1
1
2
2
3
Y. Satoh , Y. Otsubo , G. Pagès , J. Pouysségur , S. Endo , T. Kazama
1
1
2
Anesthesiology, National Defence Medical College, Tokorozawa, Japan, Institute of Developmental
Biology and Cancer Research, University of Nice Sophia-Antipolis, Centre National de la Recherche
3
Scientifique, Nice, France, Aging Regulation Research Team, Tokyo Metropolitan Geriatric Hospital
and Institute of Gerontology, Tokyo, Japan
Aim of Investigation: Extracellular signal-regulated kinase (ERK) has an important role in
neuropathic pain. However, the specific contribution of ERK2 isoforms to pain plasticity is not
necessarily elucidated. The aim of the investigation is to clarify the function of ERK2 in pain plasticity
using Erk2 conditional knockout (Erk2 CKO) mice.
Methods: Erk2 CKO mice were generated using the Cre-loxP system to cause a conditional, regionspecific, genetic deletion of Erk2. To induce recombination in the CNS, Erk2 floxed mice were crossed
with nestin promoter-driven cre transgenic mice. Resultant Erk2 CKO mice and Erk2 littermate were
subjected to mouse pain models.
Results: Erk2 CKO mice showed a normal baseline paw withdrawal threshold to mechanical stimuli.
However, these mice showed a reduced nociceptive response after formalin injection to the hind paw
and attenuated mechanical allodynia in a PSNL model compared with control mice. In Erk2 CKO
mice, compensatory hyperphosphorylation of ERK1 was detected in the spinal cord. However, the
systemic inhibition of ERK phosphorylation using the MEK inhibitor SL327 did not produce additional
changes in formalin-induced spontaneous behaviors in Erk2 CKO mice, indicating that ERK1
hyperphosphorylation did not influence nociceptive processing.
Conclusions: Our results indicate that ERK2, but not ERK1, plays a predominant and/or specific role
in pain plasticity.
861
EFFECTS OF ESLICARBAZEPINE ACETATE ON PAW WITHDRAWAL THRESHOLD IN A
MOUSE MODEL OF CHRONIC CONSTRICTION NERVE INJURY (CCI)
1
2
1
2
1,3
A.I. Loureiro , F.-Y. Zhao , L.C. Wright , D. Spanswick , P. Soares-da-Silva
1
2
Bial, Portela & Cª SA, S. Mamede do Coronado, Portugal, University of Warwick, Coventry, UK,
University of Porto, Porto, Portugal
3
Background and aims: Eslicarbazepine acetate (ESL) was approved in Europe in 2009 as
adjunctive therapy in adults with partial-onset seizures, with or without secondary generalization. In
humans and mice, ESL is rapidly and almost completely metabolized to eslicarbazepine via extensive
hydrolytic pre-systemic first-pass metabolism. This study evaluated the analgesic effects of orally
dosed ESL (50, 100, 150 and 200 mg/kg), on the paw withdrawal threshold (PWT) and compared
these effects with those of dose vehicle and gabapentin (100 mg/kg), in a mouse model of chronic
constriction nerve injury (CCI).
Methods: The baseline PWT was examined using a series of graduated von Frey hairs on 3
th
th
th
consecutive days before surgery and re-assessed on the 7 day after surgery and on the 14 to 16
days before compound dosing.
Results: The ESL vehicle did not affect PWT in CCI model mice. Gabapentin, at 100 mg/kg,
produced a significant increase in PWT in CCI model mice. ESL dose-dependently increased PWT in
the ipsilateral limbs in CCI model mice and did not significantly affect the PWT in the contralateral
side. Plasma bioanalysis showed that ESL was completely metabolized within 1 hour after
administration to mainly eslicarbazepine in a dose-dependent manner. ESL displayed potency and
efficacy similar to the reference compound gabapentin.
Conclusions: These results suggest that orally administered ESL has an anti-allodynic action in the
chronic constriction nerve injury model of neuropathic pain in mice.
862
STUDY OF THE SITE(S) OF ACTION OF ESLICARBAZEPINE ON ECTOPIC DISCHARGE IN A
MOUSE MODEL OF CHRONIC CONSTRICTION NERVE INJURY
1,2
3
1
1
P. Soares-da-Silva , F.-Y. Zhao , A.I. Loureiro , L.C. Wright , D. Spanswick
1
2
3
3
Bial, Portela & Cª SA, S. Mamede do Coronado, University of Porto, Porto, Portugal, University of
Warwick, Coventry, UK
Background and aims: Eslicarbazepine acetate (ESL) was approved in Europe in 2009 as
adjunctive therapy in adults with partial-onset seizures. In humans and mice, ESL is rapidly and
almost completely metabolized to eslicarbazepine. This study evaluated the effects of eslicarbazepine
on ectopic discharge of peripheral nerve filaments and spontaneous activity of dorsal horn neurones
in a mouse model of chronic constriction nerve injury (CCI).
Methods: The baseline paw withdrawal threshold (PWT) was examined using a series of graduated
th
th
von Frey hairs on 3 consecutive days before surgery and re-assessed on the 7 and on the 14 days
after surgery, before electrophysiological recording.
Results: Eslicarbazepine (100 mg/kg, i.p.) significantly inhibited ectopic discharge in peripheral
nerves of CCI adult male BL CB F1 mice. The effects of eslicarbazepine were similar on ectopic
discharge generated either at the neuroma or dorsal root ganglion level. In further experiments,
eslicarbazepine (100 mg/kg, i.p.), significantly inhibited spontaneous activity of dorsal horn neurones
in CCI mice. The effects of eslicarbazepine were similar in three CCI preparations with or without
spinalisation and following dorsal root section. After eslicarbazepine administration (100 mg/kg, i.p.),
maximal concentrations in plasma were detected at 30 min and then declined to half-maximal
concentrations at 2 hours. Eslicarbazepine maximal concentrations in brain and spinal cord were
observed at 30 min after administration and remained stable at 2 hours post administration.
Conclusions: Eslicarbazepine acts at the level of the central nervous system, spinal cord level, as
well as at the level of the peripheral nervous system.
863
SLEEP DISORDERS IN A MODEL OF FIBROMYALGIA INDUCED BY RESERPINE
1
2
1
1
1
A. Valverde-Amador , C. Tornero Tornero , A. Blasco-Serra , A. Cervera-Ferri , F. Escrihuela-Vidal ,
1
1
1
1
A. Taberner-Cortés , C. Blasco-Ausina , V. Teruel-Marti , T. Hernandez-Gil-de-Tejada , F. Martinez1
Soriano , Group for the Study of Anatomical Substrate of Pain and Analgesia
1
2
Human Anatomy and Embryology, University of Valencia, Anesthesia, Hospital Clínico Universitario
de Valencia, Valencia, Spain
Background and aims: The advances in neuroimaging and neurophysiological techniques show that
the patients with fibromyalgia have pain amplification at the CNS. Control of this system is mediated
by monoamine neurotransmitters and they are abnormally decreased in the cerebrospinal fluid of
such patients.
Methods: The monoaminergic system is also involved in the regulation of sleep and mood which
would explain, at least in part, the high prevalence of sleep disorders and/or depression in
fibromyalgia patients.
Recently, it has been proposed a model of fibromyalgia in rats based on central monoamine depletion
through the administration of reserpine. To have a valid model of fibromyalgia in experimental animals
is critical for advancing our knowledge of this syndrome.
This experimental model produced a decline in perceptual thresholds of pain and symptoms of
depression. Our goal is to check whether it also causes sleep disturbances. To do this, we evaluated
electroencephalographic and electromyographic patterns during sleep of reserpine-treated rats using
a chronic electrode implantation.
Results: Our results show an excess of hippocampal theta rhythm during most of the sleep period,
indicating a predominance of REM phase with a decrease of the slow waves phase.
These results, combined with the state of hypersomnia presented during wakefulness period, indicate
the presence of restless sleepin the fibromyalgia model used, which reinforces the validity of the
reserpine-induced fibromyalgia model.
Conclusions: These data suggest a disturbance of monoamines in the genesis of fibromyalgia and
point drugs such as duloxetine, a selective inhibitor of serotonin and norepinephrine, as the basis for
its treatment.
864
RELIABILITY OF QUANTITATIVE SENSORY TESTS IN A LOW BACK PAIN POPULATION
1
2
1
1
1
1
P. Vuilleumier , J. Biurrun Manresa , Y. Ghamri , A. Siegenthaler , S. Mlekusch , C. Oehler , L.
2
1
Arendt-Nielsen , M. Curatolo
1
2
Bern University Hospital, Bern, Switzerland, University of Aalborg, Aalborg, Denmark
Background: Reliability is essential when quantitative sensory testing (QST) is used for clinical and
research purposes. Most previous studies have addressed reliability in healthy volunteers, but the
results are not necessarily applicable to patients. We evaluated the reliability of multiple QST
assessments in chronic low back pain patients.
Methods: 107 chronic low back pain patients were analyzed after undergoing two identical
experimental sessions, 7-21 days apart. Performed measures were: pressure pain detection and
tolerance thresholds, single and repeated (temporal summation) electrical pain thresholds, pain
intensity after electrical stimulation, heat pain detection and tolerance thresholds at the arm and leg,
cold pain detection thresholds at the arm and leg, and conditioned pain modulation using ice water as
conditioning and pressure stimulation as test stimulus. Reliability was analyzed with the Coefficient of
Variation (CV) and the Intra-class Correlation Coefficient (ICC).
Results: The results of the best 8 tests are shown in the table.
Electrical
single
stimulation
pain
threshold
Electrical
repeated
stimulation
pain
threshold
Pressure
pain
detection
threshold
toe
Pressure
pain
tolerance
threshold
toe
Heat pain
detection
threshold
arm
Heat pain
tolerance
threshold
arm
Heat pain
Conditioned
detection
pain
threshold
modulation
leg
Intra-class
correlation 0.80
coefficient
0.80
0.78
0.77
0.70
0.72
0.59
0.64
Coefficient
of
23.1%
variation
23.0%
18.3%
15.9%
5.7%
2.3%
4.1%
22.4%
[Results for the best 8 tests.]
Conclusions: Reliability of QST measures was in most cases suitable for experimental and clinical
purposes. The largest variations were observed in cold pain detection thresholds, heat pain tolerance
threshold at the leg and pain intensity after electrical stimulation.
865
EXPERIMENTAL ASSESSMENT OF THE EFFECTS OF PAIN AND OPIOIDS ON COGNITIVE
FUNCTION
1,2
3,4
3
4
3
5
1
G.P. Kurita , L.P. Malver , T. Andresen , R. Polianskis , A.M. Drewes , L. Christrup , J. Højsted ,
2,6
P. Sjøgren
1
2
Multidisciplinary Pain Centre, Section of Palliative Medicine, Rigshospitalet, Copenhagen University
3
Hospital, Copenhagen, Department of Gastroenterology, Mech-Sense, Aalborg Hospital,
4
5
Multidisciplinary Pain Centre, Aalborg Hospital, Aalborg, Dept. Drug Design and Pharmacology,
6
Faculty of Health and Medical Sciences University of Copenhagen, Dept. Clinical Medicine, Faculty
of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Background and aims: Pain and opioids are frequent in cancer, but their interference on patients'
cognitive function is not clear. This study aimed to analyse the effects of pain and remifentanil on
sustained attention (SA).
Methods: Randomized, double-blind, placebo controlled, crossover study with 22 healthy Caucasian
male volunteers (20-28y). SA, the ability to respond rapidly to external stimuli for an extend period of
time, was evaluated by a Continuous Reaction Times (CRT) software. Three experiments were
conducted.
1st experiment: CRT was tested under the influence of experimental pain of mild and moderate
intensities induced by an electronic pneumatic tourniquet cuff;
2nd experiment: CRT was tested under the influence of placebo (saline) or remifentanil;
3rd experiment: CRT was tested under pain relief with remifentanil or placebo as well as pain increase
(breakthrough pain). Assessments occurred when the volunteers reported stable pain or 10 minutes
after steady-state infusion. Study approved by Ethics Committee.
Results:
1st experiment: moderate and mild pain slowed CRT significantly from baseline, but there were no
differences when comparing pain intensities.
2nd experiment: slower performance on remifentanil when compared to placebo (P≤0.007).
3rd experiment: decrease in pain intensity with remifentanil while placebo effect was minimal (P<
0.001); volunteers had slower CRT on remifentanil ( P≤0.02). Additional effect prolonging CRT was
observed during breakthrough pain (P=0.045).
Conclusions: Both pain and remifentanil alone deteriorated SA. Remifentanil relieving pain also
deteriorated SA; however, breakthrough pain superimposed on controlled pain further deteriorated
SA.
The study is supported by The Danish Cancer Society.
866
INFLUENCES OF CPP THE ABILITY FUNCTIONAL (WORK) IN WOMEN FOLLOWED UP IN THE
OUTPATIENT PAIN HCFMRP - USP, BRAZIL
B. Mellado, A.M. Falcone, F.C. Reis
Gynecology and Obstetrics, University of São Paulo- FMRP, Ribeirao Preto, Brazil
Background and aim: The Chronic pelvic pain (CPP) is defined as continuous or intermittent pain in
the pelvic region, not exclusively related to the menstrual flow or sexual intercourse Our objective is to
explore the experience of women with CPP, knowing how this routine pain can interfere in their
married life, social, financial (business), as well as activities of daily living.
Methods: This is a qualitative study based on interviews through focus groups. Fifteen women were
included in three focus groups with five of these women in each. All of them had confirmed diagnosis
of endometriosis by laparoscopy, and at least six months of follow.
Results: One of the factors mentioned by women during the interviews was referring to the fact that
they are no longer economically active, since the continuous and persistent pain prevents them from
meeting the workload established by the employer. Thus women report feelings of being a burden to
their family and also the feeling of uselessness. Besides not being able to work these women have no
right to disability retirement by the National Social Security.
Conclusion: Women with CPP have lower family incomes compared to women without CPP due to
disability caused by continuous and persistent symptoms of pain.
867
THE UVB INFLAMMATORY PAIN MODEL: A REPRODUCIBILITY STUDY IN HEALTHY
VOLUNTEERS
1
2
1
1
1
1
C.D. Mørch , A. Rahi , L.R.B.U. Christensen , P. Gazerani , T.A. Nielsen , L. Arendt-Nielsen
1
2
Center for Sensory-Motor Interaction (SMI), Aalborg University, Center for Clinical and Basic
Research (CCBR), Aalborg, Denmark
Background and aims: The ultraviolet-B (UVB) experimental pain model is widely used for induction
of cutaneous inflammation involving hyperalgesia and neurogenic inflammation. The aims of the study
were to 1) validate the UVB-model by investigating the test-retest reliability using a variety of
quantitative pain and vasomotor assessments and 2) to estimate sample-sizes for a parallel and a
cross-over pharmacological studies applying the UVB model.
Methods: A circular area (5cm diameter) on the upper arms of 15 healthy male volunteers was
irradiated by UVB (three times of the minimal erythema dose). Neurogenic inflammation was
assessed by measuring erythema, superficial blood flow and skin temperature. Primary hyperalgesia
was assessed by measuring heat pain threshold, pressure pain threshold, brush-evoked allodynia,
and pinprick hyperalgesia (stimulus-response function) at baseline, 24h, 48h and 72h post irradiation.
The experiment was repeated on the contralateral arm after 2 weeks. Coefficient of variation (CV),
and intra-class correlation (ICC) were calculated for between and within session assessments. The
sample-size need to detect a 20% difference between baseline and post irradiation was calculated for
parallel (N-par) and cross-over (N-co) designs.
Results: Erythema was the most reproducible assessment of neurogenic inflammation (ICCwithin:
0.50, ICCbetween: 0.63; CVwithin: 6%, CVbetween: 8%; N-par: 6; N-co: 4), and 60 g pin-prick
stimulation was the most reproducible sensory assessment (ICCwithin: 0.76, ICCbetween: 0.54;
CVwithin: 8%, CVbetween: 9%; N-par: 26; N-co: 7).
Conclusion: The UVB-induced neurogenic inflammation and sensory changes are reproducible and
stable for three days allowing for cross-over study designs with a small sample-size.
868
THE CONTRIBUTION OF THE THORACOLUMBAR FASCIA TO CHRONIC LOW-BACK PAIN IN
HUMANS
A. Schilder, W. Magerl, U. Hoheisel, R.-D. Treede
Department of Neurophysiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim,
Germany
Background and aims: Animal studies suggested that the thoracolumbar fascia (TLF) is involved in
the development of low-back pain (LBP). The current study aimed to investigate the role of this
particular tissue type as a potential source of chronic LBP. Here, long-term potentiation effects (LTP)
induced by high frequency stimulation (HFS) served as a model for chronic pain.
Methods: Four bipolar concentric needle electrodes in total were bilaterally placed at lumbar level
(L3/L4) into the multifidus muscle and into the overlying thoracolumbar fascia of sixteen healthy
volunteers (24±0.5 years (mean±SEM); 8w).
HFS (5 x 1s x 100Hz) was applied in order to induce LTP. The detection- and pain thresholds (ID and
IP) were determined for each tissue and needle pre- and post-HFS followed by single stimuli (2xIP).
Pain intensities and pain qualities were determined for single-electrical pulses.
Results: After HFS in the TLF, pain evoked by single electrical pulses through the HFS electrode
increased significantly to ~50% above baseline (P< 0.001 vs. control). No such facilitation was seen in
the muscle. Furthermore, ID increased significantly after muscle- and fascia HFS (P< 0.01 and P<
0.05, respectively). Single electrical pulses within the fascia revealed pain qualities such as “scalding”,
“stinging” and “hot”, whereas muscle stimulation was described as “crippling”, “beating”, “throbbing”
and “dull”.
Conclusion: HFS can induce LTP when applied in the TLF. Thus, this study illustrates a potential
contribution of fascia tissue to the development of chronic LBP.
Funded by the Federal Ministry of Education and Research (Grant # 01EC1010B).
869
MOLECULAR IDENTIFICATION OF A NOVEL POPULATION OF ITCH RECEPTORS
1
1
1
2
1
K.K. Stantcheva , R. Dhandapani , L. Iovino , T. Paparountas , D. Bilbao , P. Heppenstall
1
1
2
EMBL Monterotondo, Monterotondo, Dulbecco Telethon Institute, Rome, Italy
Background and aims: Itch is an unpleasant sensory experience mediated by specific subtypes of
cutaneous sensory neurons. Here we have identified and characterized a novel population of itch
receptive sensory neurons in the mouse.
Methods: We performed Fluorescently Activated Cell Sorting (FACS) of mouse DRG neurons
followed by transcriptional profiling to isolate functionally discrete populations of sensory neurons. We
focused on a population of putative itch receptors and characterized their function using histology,
calcium imaging and behavioral experiments.
Results: We identified a novel subset of sensory neurons that displayed a distinct molecular
signature characterized by high expression levels of receptor/signaling complexes that mediate itch in
both normal and pathological conditions. We mapped the anatomical projection patterns of these
neurons and determined that they terminate in lamina II inner of the dorsal horn. We further examined
their pharmacological profile and identified molecules that exclusively activate this novel subset.
Remarkably, we found that subcutaneous application of these compounds to mice evoked scratching
behavior, most likely mediated by these neurons.
Conclusions: We have identified a novel population of itch receptive sensory neurons that display a
unique molecular signature and anatomical projection pattern. Further analysis of this population and
its expression profile is likely to reveal novel targets for its inhibition and potentially for the treatment of
chronic itch.
248
IMPACT OF EMOTION REGULATION ON CHRONIC POSTSUGICAL PAIN IN PATIENT WITH
BREAST CANCER
1
1
2
2
1
1
S. Baudic , A. Masselin-Dubois , A. Albi-Fredzer , C. Jayr , D. Bouhassira , N. Attal
1
2
U987 INSERM Pain Research Unit, Boulogne, Hôpital René Huguenin - Institut Curie, St-Cloud,
France
Aim of investigation: Persistent pain is a major complication of surgery for breast cancer and has a
deleterious impact on quality of life. Despite the importance of emotion in this pathology few studies
have prospectively investigated the role of emotion regulation strategies in the development of chronic
pain. The objective is to examine emotion dysregulation in the development of chronic pain after
breast cancer surgery (BCS) and it relationship with anxiety and depression.
Methods: A total of 100 women (aged 18 to 85 years) scheduled for radical mastectomy (n = 64) or
lumpectomy with axillary node dissection (n = 36) were evaluated prospectively before and after
surgery. Emotion dysregulation (Toronto Alexithymia Scale, Weinberger Repression Questionnaire),
anxiety (State-Trait Anxiety Inventory), depression (Beck Depression Inventory), psychological
adjustment (Cancer Locus Control Scale, Body Image Scale) and Catastrophizing (Pain
Catastrophizing Scale) were assessed. Intensity of pain was evaluated by the Brief Pain Inventory.
Results: The percentage of the patients who reported at least moderate pain (≥ 3/10) at three, six
and twelve months was 14%, 20% and 18%, respectively. Patients with chronic pain reported higher
levels of depression, anxiety and alexithymia related to painless patients. Multivariate regression
analyses showed that the presence of chronic pain was predicted by anxiety at three and six months
and by alexithymia at three, six and twelve months.
Conclusions: Our study supports the predictive value of alexithymia, a disorder of emotion
regulation, in the development of persistent pain after BCS, independently of anxiety and depression.
249
FELLING HURT: SOCIAL REJECTION MODULATES SENSORY DIMENSIONS OF PHYSICAL
PAIN
1,2
3
R. Canaipa , J.M. Moreira , A. Castro Caldas
1
1
2
3
Health Science Institute, Portuguese Catholic University, Faculty of Medicine, Faculty of
Psychology, University of Lisbon, Lisbon, Portugal
Background and aims: It is assumed that social pain, resulting from injury of social bonds, may have
co-opted the neuroanatomical bases of the emotional aspects of pain experience (Eisenberger et al.,
2003). A recent paper, however, has shown that social pain may also involve the sensory areas
(Kross et al., 2011). Therefore, the current study, employing electrical stimuli, aims to investigate
whether a social pain manipulation shows impact on sensory dimensions of physical pain and to
understand the impact of psychological characteristics on susceptibility to pain.
Methods: 33 healthy participants answered questionnaires measuring a number of physical and
psychological characteristics. After obtaining their electrical pain threshold (in terms of intensity of
pain) participants played Cyberball, a virtual ball tossing game designed to manipulate social rejection
feelings. After this manipulation, they were exposed to painful stimuli, and rated their intensity and
unpleasantness. It was hypothesized that rejected participants would rate stimuli as more intense and
more unpleasant.
Results: Rejected individuals felt greater pain intensity when compared to non-included and included
participants.This effect was mediated by low control perceptions in the Cyberball situation.Pain was
correlated with perceived life stress and low feelings of personal efficacy.
Conclusions: Social rejection changes intensity ratings of physical pain derived from rapid nerve
fibers. This effect lasts after the rejection situation and is apparently mediated by feelings of low
control and efficacy in social situations. These results show that social rejection may impact on
sensory, and not only emotional, dimensions of physical pain.
250
PAIN INTENSITY AND PERCEIVED INJUSTICE IN CHRONIC PAIN PATIENTS
1,2
2,3
2
1
2
A.-F. Allaz , D. Rentsch , M. Besson , M. Kossowski , V. Piguet , C. Cedraschi
2,4
1
Division of General Medical Rehabilitation, Beau-Séjour Geneva University and GUH,
3
Multidisciplinary Pain Centre, Division of Clinical Pharmacology and Toxicology, GUH, Division of
4
Consultation Liaison Psychiatry, Geneva University Hospitals (GUH), Division of General Medical
Rehabilitation, Geneva University and GUH, University Hospital Geneva, Geneva, Switzerland
2
Background: According to recent publications, a high level of perceived injustice is associated with
pain severity in patients with musculoskeletal injury or fibromyalgia.
The aim of our study was to investigate whether perceived injustice has an impact on pain intensity in
unselected chronic pain patients and whether it modified their views about the possibility of pain
disappearance.
Methods: A self-administered questionnaire was given to all patients referred to our pain centre
during a one year period. Present pain was evaluated on a visual analog scale (0-10cm). Depression
was evaluated with HAD. The feeling of injustice associated with pain was assessed by the
question:”do you consider your pain as an injustice” (5-point Likert scale). Patients were asked about
the likelihood of pain disappearance (4-point Likert scale). Multivariate linear regression analysis
evaluated which variables were associated with pain intensity.
Results: 421 patients were included. Mean age was 53 (SD=19), 64% women. Median pain duration
was 7 years (0.3-50); mean pain intensity was 6.7 (SD=2.5). Pain was “always” or “often” considered
as an injustice by 173 (41%) patients; 147 (35%) evaluated pain disappearance as “unlikely” or
“impossible”.
High perceived injustice (Coeff=0.25; 95%CI 0.09-0.42) and high depression scores (Coeff=0.13;
95%CI 0.08-0.18) were independently associated with an increase in pain intensity. Both significantly
decreased the estimated likelihood of pain disappearance, independently from pain intensity.
Conclusions: Our findings confirm the relevance of perceived injustice in the assessment of chronic
pain patients as this dimension is associated with pain intensity and pessimistic assessment of pain
disappearance.
251
DEPRESSION IN LOW BACK PAIN: THOUGHT-SUPPRESSION X STRESS INTERACTION
PLAYS A ROLE IN FEMALE, NOT IN MALE PATIENT
1
1
1
1
2
3
M. Hasenbring , D. Hallner , A.C. Rusu , N. Kreddig , R. Willburger , I. Streitlein-Böhme , H.
4
Rusche
1
2
Dept. of Medical Psychology and Sociology, Dept. of Orthopaedics, Elisabeth Hospital, Ruhr3
University of Bochum, Faculty of Medicine, Bochum, University of Freiburg, Faculty of Medicine,
4
Freiburg im Breisgau, Dept. of Family Medicine, Ruhr-University of Bochum, Faculty of Medicine,
Bochum, Germany
Background and aims: Depression plays a significant role in the maintenance of low back pain and
disability. Notwithstanding, little is known about the mediating mechanisms. Besides genetic
predisposition, individual styles of emotion regulation may play an important role. Thought
suppression is a common cognitive response to negative thoughts and sensations known to increase
emotional distress by frequent failures and rebound. Recent studies indicated thought suppression
may increase depressive mood especially when it is shown in interaction with high emotional distress.
Methods: 177 patients with sub-acute back pain from primary care practices completed a set of
questionnaires (Subscale Thought Suppression TSS from the Avoidance-Endurance-Questionnaire
AEQ, Beck Depression-Inventory BDI, Stress-Ressources Inventory SRI). Using median split, patients
were distinguished into high versus low TSS and stress, respectively. A three-way analysis of
variance calculated main effects for thought suppression, stress and gender as well as possible
interactions with BDI-depression as dependent, using SPSS-21.
Results: Results indicated significant main effects for gender (p < .05) and stress (p < .01) with higher
depression scores in women and in patients showing high stress. Further, a significant thought
suppression x stress x gender effect was found: depression was elevated in female patients showing
high thought suppression and high stress (p < .05). This effect was not seen in male patients.
Conclusions: Maladaptive emotion-regulation strategies such as thought suppression might
contribute to elevated depression in female patients when accompanied with high stress in daily life.
252
CHRONIC PAIN: YOU DO NOT SUFFER AN ANXIETY-DEPRESSION STATE BUT YOUR PAIN
HAVE AN IMPACT ON YOUR MOOD
F. Marchand, N. Mimassi
Centre d'Evaluation et de Traitement des Douleurs- Site Morvan, CHRU de Brest, Brest, France
The term of depression delivered through an assessment of chronic pain is inadequate. Depression
responds to a precise clinical definition. Gradually, depression is used out of its framework.
Objectives: To show the negative impact of a diagnosis of depression in chronic pain patients.
Methods: 21 patients with chronic pain. Cognitive test. 9 items defining clinical depression:
permanent sleep disorders, eating disorders, depressed mood, cognitive impairment, psychomotor
slowing, suicidal thoughts, loss of interest, loss of energy, guilt.
Results: 19 patients. Time evolution of chronic pain > 24 months, 18 with normal cognitive test. 17
patients did not meet the criteria for clinical depression.
Discussion: Term and diagnosis of depression should be used only in their specific clinical settings.
The attention must go primarily to the evaluation of cognitive function. Results confirm that chronic
pain is the cause of mood disorders but not of a clinical state of depression. The patient refuses this
diagnosis that involves treatment adherence against the main reason pain monitoring.
Depression also has a very negative impact on our society in which any mental disorder is
stigmatized. We must avoid drag to this diagnosis and keep to the depression its own references. In
practice, we suggest asking the patient to write himself the impact on the mood of his chronic pain, to
analyze the cognitive and psycho-emotional status.
Finally, pharmacologists should take over the classification of inhibitors of serotonin and
norepinephrine to separate a therapeutic class used in chronic pain from that used in the anti
depressant treatments.
253
ARE PSYCHOLOGICAL PREDICTORS OF CHRONIC POSTSURGICAL PAIN DEPENDENT ON
THE SURGICAL MODEL? A COMPARISON OF TWO SURGICAL MODELS
1
1,2
A. Masselin-Dubois , N. Attal , D. Fletcher
1,2
Baudic
1,2,3
4
4
5
1,2
, C. Jayr , A. Albi , J. Fermanian , D. Bouhassira , S.
1
INSERM U-987, CHU Ambroise Paré, GH Paris Ile de France Ouest, APHP, Boulogne-Billancourt,
3
Université Versailles-Saint Quentin, Versailles, Service d'Anesthésie-Réanimation Chirurgicale,
4
CHU Raymond Poincaré, GH Paris Ile de France Ouest, APHP, Garches, Service de Chirurgie
5
Générale, Hôpital René Huguenin-Institut Curie, Saint Cloud, Service de Biostatistiques, CHU
Necker, APHP, Paris, France
2
Background: Anxiety, depression and catastrophizing are generally considered to be predictive of
chronic postoperative pain, but this may not be the case after all types of surgery. This raises the
possibility that the results depend on the surgical model.
Methods: We assessed the predictive value of these factors for chronic postsurgical pain in two
surgical models: total knee arthroplasty for osteoarthritis (89 patients, 65% women, aged 69 ± 9
years, presurgical pain in 87 % of cases) and breast surgery for cancer (100 patients, 100% women,
aged 55 ± 12 years, no preoperative pain). Data were collected before surgery, two days and three
months after surgery. Anxiety, depression and catastrophizing were measured with the Spielberger
State-Trait Anxiety Inventory, Beck Depression Inventory and Pain Catastrophizing Scale,
respectively. Pain was assesssed with the Brief Pain Inventory. Neuropathic pain was detected with
the DN4 questionnaire.
Results: Multivariate logistic regression analyses for the total sample of patients indicated that the
presence of clinically meaningful chronic pain at three months (pain intensity ≥ 3/10) was predicted
independently by age (p = 0.04), pain intensity on day 2 (p = 0.009) and state anxiety (p =0.001).
Linear regression models also showed that pain magnification, one dimension of catastrophizing,
independently predicted pain intensity (p = 0.04). These results were not affected by the surgical
model or the neuropathic characteristics of pain.
Conclusion: State anxiety and pain magnification seem to constitute psychological risk factors for
chronic postsurgical pain relevant in all surgical models.
254
4-METHYLCATECHOL (4-MC), BDNF INDUCER, AMELIORATES CHRONIC PAIN WITH
DEPRESSION VIA. PREVENTION OF TRKB RELATED SIGNALING
1
2
2
2
3
2
O. Nakanishi , K. Ishikawa , K. Fukuhara , S. Yasuda , M. Yoshida , T. Ishikawa
1
2
3
Dental Anesthesiology, Dentistry Support Center, Kitakyushu, Yamaguchi University, Ube, Dental
Anesthesiology, Kyushu Dental College, Kitakyushu, Japan
Aims: Depression and anxiety are commonly complicated in chronic pain and negatively affect the
QOL. Recent studies clearly demonstrated that a lack of BDNF can lead pain-emotion and cingulated
cortex (ACC) is activated shown by brain imaging. The activated ERK in ACC is required for painemotion. 4-methylcatechol (4-MC) is induced BDNF, but the role of the BDNF in neuropathic pain is
poorly understood. Thus, we aimed to characterize the role of 4-MC on ERK related to BDNF mRNA
in chronic pain.
Method: Sprague-Dawley rats were subjected to CCI model. We measured sensory and emotional
function using Plantar testing (PWL) and a forced swimming testing (immobility time) during chronic
stage. 4-MC was icv. injected and anti-BDNF, K252a (TrkB blocker) was co-delivered to ensure these
effects. Rats were perfused fixation with 4% para-formaldehyde for pERK1/2(immunohistochemistry)
and BDNF mRNA (RT-PCR).
Result: During chronic pain stage, the rats showed decrease in PWL associated with extended
immobility time. The pERK1/2 increased in spinal cord and ACC, and the BDNF mRNA decreased in
ACC in chronic phase. 4-MC reduced depression and chronic pain, and that was similar to action of
the MEK1/2 inhibitor.
Conclusions: Based on this study, 4-MC, stimulator of BDNF synthesis, prevent the pain-emotion in
chronic pain via. preventing trkB receptor coupled signaling, ERK-BDNF mRNA. Moreover, further
support that pain and mood regulation share mechanisms and thus 4-MC is therapeutic targets.
255
DAY-TO-DAY VARIABILITY OF EMOTIONS IN CHRONIC PAIN
1
2
3
1
2
S. Rost , D.M.L. Van Ryckeghem , P. Koval , S. Sütterlin , G. Crombez
1
2
Research Unit INSIDE, University of Luxembourg, Walferdange, Luxembourg, Ghent University,
3
Gent, KULeuven, Leuven, Belgium
Background and aims: Most often, pain research has focused on patients' mean symptom levels
and does not take into account the dynamic nature of everyday life experiences. This study
investigated the relationship between day-to-day fluctuations of emotions and
(1) pain outcomes and
(2) particular individual differences (i.e. depression, anxiety, coping strategies, illness cognitions) in
chronic pain patients.
Methods: Participants were 74 chronic pain patients (Mage = 50; 49 females). In a first phase,
participants completed a number of self-report measures concerning acceptance, helplessness, pain
severity and pain disability. The subsequent phase consisted in the assessment of daily mood
(positive/negative affect) and pain perception, measured for a duration of two weeks by means of an
electronic diary. RMSSD (root mean square successive difference) was calculated as an index for
emotional instability.
Results: Results indicated a negative association between the instability (RMSSD) of negative affect
and acceptance (r = -.33, p < .05). Helplessness (r = .30, p < .05), pain severity (r = .28, p < .05) and
pain disability (r = .32, p < .01) were positively related to the instability of negative affect. No
associations were found for the instability of positive affect.
Conclusions: Results point to a relation between the instability of negative affect and pain outcomes
in chronic pain patients. These findings may have clinical implications and open new research
directions to explore whether the reduction of the instability of negative affect may be an important
target in therapeutic interventions for chronic pain patients.
256
INFLUENCE OF SLEEP DISORDERS ON THE SEVERITY OF CHRONIC PAIN: AN
INVESTIGATION INTO THE ROLE OF SPECIFIC SLEEP DISORDERS
1
2
1
M. Hornyak , H. Scholz , R. Thoma , D. Riemann
1
2
2
Algesiologikum - Zentren für Schmerzmedizin, München, Universität Freiburg, Freiburg im Breisgau,
Germany
Background: Chronic pain (CP) patients often show symptoms of insomnia and affectiv symptoms
which have a negative influence on pain perception. Specific sleep disorders such as restless legs
syndrome (RLS) and sleep apnea syndrome (SAS) lead to a marked sleep impairment and are
prevalent in CP. In this study, the associations between sleep problems, affective symptoms, and pain
severity were assessed in CP patients with insomnia and with RLS and SAS by structure equation
modelling.
Methods: 814 consecutively recruited chronic pain patients of two German pain centres were
evaluated. Pain severity, sleep problems, depressive and anxiety symptoms were assessed.
Additionally, patients were screened for RLS and SAS by means of validated diagnostic
questionnaires. Structure equation modelling of the data was performed.
Results: In CP patients with non-specific insomnia, sleep problems were associated with depressive
symptoms and with pain intensity. CP patients with RLS showed only an association between sleep
and depressive symptoms and with anxiety symptoms and pain intensity. CP patients positive for SAS
show associations between sleep problems and depressive symptoms and between sleep problems
and pain intensity.
Conclusions: In CP patients with non-specific sleep disorders, depressive symptoms partly mediate
the association between sleep problems and pain intensity. Anxiety symptoms seem to mediate the
association between disturbed sleep and pain intensity in RLS. Non-restorative sleep in CP patients
positive for SAS appears to lead to depressive symptoms as well as to increased pain intensity.
257
THE EFFECT OF HUNGER ON PAIN: A LASER-EVOKED POTENTIAL STUDY
1
1
1
2
H. Wright , X. Li , N. Fallon , T. Giesbrecht , A. Stancak
1
1
2
Pain Research Group, University of Liverpool, Liverpool, UK, Unilever R&D, Vlaardingen, The
Netherlands
Background and aims: Hunger and pain are basic homeostatic drives that compete for behavioural
responses when experienced together. To investigate the cortical processes underlying hunger-pain
interactions, we manipulated participants' hunger and presented photographs of appetising food or
inedible objects in combination with painful laser stimuli.
Methods: 14 healthy participants completed two EEG sessions; one following an overnight fast, the
other following a large breakfast. Trials displayed photographs of either food or objects, accompanied
by a moderately painful laser stimulus to the dorsal surface of the right hand. Participants rated the
pain after each stimulus. The experiment was organised into three blocks, each containing 32 trials.
Spatio-temporal patterns of cortical activation underlying hunger-pain competition were explored
using 128-channel EEG recordings and source dipole analysis of laser evoked potentials (LEPs) in
BESA 6.0.
Results: Pain was stronger during sated than during hungry state in the first experiment block.
Source activity in right parahippocampal gyrus, modelling the N3 component of LEPs (248-257ms),
was stronger in sated than in hungry state. Additional statistically significant effects of the
photographs were found in left insula, mid-cingulate cortex, right parahippocampal gyrus, and
cerebellum. In all structures, LEPs were smaller for food than for object photographs.
Conclusions: Pain and cortical processing of noxious stimuli in parts of the limbic cortex are
attenuated in hungry state, suggesting competition between eating drive and pain. Cortical processing
of noxious stimuli is also attenuated by passively viewing food photographs, pointing to pain
processing being modulated by stimuli with strong motivational value.
258
COMORBID SOCIAL ANXIETY AND PAIN: RELATIONSHIP WITH TRANSDIAGNOSTIC
PSYCHOLOGICAL PROCESSES
M. Wurm, S. Larsson, K. Boersma, M. Tillfors
Center for Health and Medical Psychology, JPS, Örebro University, Örebro, Sweden
Objectives: Little is known about comorbid chronic pain and social anxiety. This is important as it
may lead to specific pain-related social challenges. Transdiagnostic psychological processes are
suggested to influence the comorbidity of anxiety disorders and pain. Research is needed to study
whether similar processes might be present for those with comorbid pain and social anxiety.
Aim: To examine the co-occurrence of social anxiety and pain-related fear in a pain-sample and to
describe this group on transdiagnostic factors.
Method: A cross sectional study where 195 patients with chronic musculoskeletal pain seeking care
at a Swedish pain-rehabilitation clinic filled out questionnaires. Subgroups were created using cluster
analysis with Social Phobia Screening Questionnaire and Tampa Scale of Kinesiophobia. Thereafter
the subgroups were validated and described on the Multidimensional Pain Inventory, Hospital Anxiety
and Depression Scale, Anxiety Sensitivity Index and Self Consciousness Scale.
Preliminary results: The analysis revealed 4 distinct clusters with high internal homogeneity; a low
scores, a pain related fear only, a social anxiety only and a comorbid pain-related fear and social
anxiety cluster. The comorbid cluster reported significantly higher pain-intensity compared to a lowscore cluster. They had significantly higher degrees of depression, anxiety, anxiety-sensitivity and
self-consciousness compared to both the high-pain-related-fear-only and the low-scores clusters.
Discussion: A subgroup of individuals displaying high comorbidity between social anxiety and painrelated fear exists in a chronic pain sample. This subgroup has significantly higher levels on measures
that are proposed transdiagnostic psychological processes suggested to influence and maintain
problems. Implications will be discussed.
259
VISUAL BODY PERCEPTION AND NOCICEPTION: ARE THEY RELATED IN WOMEN WITH
EATING DISORDERS?
1
A. Yamamotova , H. Papezova
2
1
Department of Normal, Pathological and Clinical Physiology, Charles University in Prague,
Department of Psychiatry, Charles University in Prague, 1 st Faculty of Medicine, Prague, Czech
Republic
2
Background and aims: Growing evidence shows that body image can be distorted in people with
pain. On the other hand, disturbance of body perception is a central aspect of patients with anorexia
nervosa. Aim of our study was to analyze association between body image perception, body
dissatisfaction, and nociception in women with eating disorders (ED) and age matched healthy control
women.
Methods: Body dissatisfaction and pain perception were measured in 32 DSM-IV diagnosed patients
with ED and 30 healthy women. The pain threshold latencies on radiant heat stimuli were measured
using the Analgesia meter (IITC Life Science USA). Body image perception (BIP) and body
dissatisfaction (DIS) were measured using software Anamorphic Micro (digital pictures of their own
body image were distorted to fat-body image and thin-body images).
Results: ED patients more overestimated their body size in comparison with controls, in the
parameter DIS the two groups did not differ. Pain threshold latencies correlated with objective
dissatisfaction (calculated as Desired Size/True Image Size; in pixels) with own body in patients only
(r = 0.55, p = 0.001). In neither group measured pain characteristics correlated with BIP (Estimation
Size/True Image Size).
Conclusions: In patient with ED, pain perception is more associated with emotional but not with
sensory (visual) processing of their own body images. The more they want to be thin, the more
sensitive they are to pain. Therefore body dissatisfaction reflects negative emotions and may also
share some of the mechanisms of pain system.
Supported by: PRVOUK P34, IGA NT/14094.
260
SUCCESS OR FAILURE OF CHRONIC PAIN REHABILITATION: THE IMPORTANCE OF GOOD
INTERACTION, A QUALITATIVE STUDY UNDER PATIENTS AND PROFESSIONALS
1
2
3
4
B. Oosterhof , J.H.M. Dekker , M. Sloots , E.A.C. Bartels , J. Dekker
1
5
2
Occupational Therapy, Rehabilitation Medicine, Rehabilitation Center Heliomare, Wijk aan Zee,
4
Occupational Therapy, Amsterdam Rehabilitation Research Center, Department of Social and
5
Cultural Anthropology, VU University Amsterdam, Department of Rehabilitation Medicine, VU
University Medical Center, Amsterdam, The Netherlands
3
Background and aims: Research and clinical practice show that chronic pain patients are not always
satisfied with pain rehabilitation. Differing expectations and the presence of a poor interaction
between patient and professional seems to be the reason for this. The aim of this study was to
explore which factors are associated with a successful treatment outcome in chronic pain patients and
professionals participating in a multidisciplinary rehabilitation program, with a specific focus on the
interaction between patients and professionals.
Methods: Patients (n=16) and professionals (n=10) were interviewed and/or observed. The
transcribed interviews and observations were analysed and themes were described.
Results: Patients with a positive treatment outcome came to a shared understanding of their pain
with their professional, demonstrated new learned behavior and were able to continue their learning
process at home. Patients with a negative treatment outcome did not reach a shared understanding of
their pain with their professional, were not able to change their behavior and wanted more help to
achieve this. Both patient groups experienced organizational barriers within the treatment process.
Factors associated with a high quality of patient-professional interaction included the patient
experience of being taken seriously, the involvement of the professional with the patient, a clear
explanation of the pain, and an open interaction between patient and professional.
Conclusions: This study provides insight into the factors which lead to a positively or negatively
experienced outcome of pain rehabilitation. A good match within the patient-professional interaction
seems essential.
261
EVIDENCE FOR EXECUTIVE FUNCTION DEFICITS IN CHRONIC PAIN: A SYSTEMATIC REVIEW
AND META-ANALYSIS
1,2
1,3
1
2,4
2
C. Berryman , T. Stanton , K.J. Bowering , A. Tabor , L. Moseley
1
2
Body in Mind Research Group, Sansom Institute for Health Research, University of South Australia,
3
4
Adelaide, SA, Neuroscience Reseach Australia, Sydney, NSW, Australia, School of Biomedical
Sciences, Kings College, London, UK
Background and aims: Several lines of research suggest that chronic pain may be associated with
disrupted executive function. We aimed to undertake a systematic review to compare the performance
of people with chronic pain with that of healthy controls on standard tests of executive function.
Methods: A sensitive search was conducted to retrieve articles relating to executive function and
chronic pain following PRISMA and Cochrane Collaboration guidelines. Papers were required to
evaluate executive function and include a control group comparison. Papers were excluded if they
recruited subjects < 18 years old or populations with event-related/disease-related changes that
would likely impair cognition. Risk of bias was evaluated using a quality assessment tool.
Results: Full text for 215 papers was retrieved with 23 papers included in the review. All papers used
tests that required a behavioural response to an executive function task (one study also reported fMRI
outcomes) across eight different cognitive domains. Pooled effect estimates for time to completion
and number correct test outcomes demonstrated no difference between people with chronic pain and
healthy controls. People with chronic pain had significantly slower reaction times than healthy controls
on tests of executive function (pooled effect estimates 0.91 to 1.05 [95%CI 0.17-1.93]).
Conclusions: Consistent evidence of executive dysfunction in reaction time (across cognitive
domains) exists for people with chronic pain. That there is evidence of no impairment of number
correct or time to completion of executive function tests is surprising. A dearth of physiological
investigations into executive function limits interpretation of our findings.
262
NO IMPAIRMENT OF EXECUTIVE FUNCTION, PSYCHOMOTOR SPEED, AND DECISIONMAKING UNDER RISK IN CHRONIC LOWER BACK PAIN PATIENTS
1
2
R. Masiliunas , D. Vitkute , K. Petrikonis
1
1
2
Department of Neurology, Lithuanian University of Health Sciences, Kaunas, Lithuania, Klinik
Kircheim, Kreiskliniken Esslingen, Esslingen, Germany
Clinical studies suggest that cognitive functions are impaired in chronic pain patients. However, there
is no obvious common pattern between studies. The aim of our study was
(1) to evaluate how executive function, psychomotor speed and decision-making under risk are
altered in chronic lower back pain patients and
(2) to answer the question if impaired decision-making is due to cognitive dysfunction or other
reasons, such as impaired reward processing.
We examined 27 patients aged 49 to 69 with chronic lower back pain (CLBP >6 months, with a mean
of 91 months, SD = 160) and 30 healthy volunteers, matched for age, sex, and education. Pain was
evaluated by Visual Analogue Scale, Pakula Pain Questionnaire (Lithuanian analogue of McGill Pain
Questionnaire), and Fibromyalgia Tender Points Examination. A battery of neuropsychological tests
were used to measure cognitive performance. CLBP patients did not score significantly worse in any
examined neuropsychological tests. Neither pain duration, nor subjective pain scores correlated with
any of the cognitive domains. Psychomotor speed was the only domain that correlated inversely with
the number of affective pain descriptors. Since Game of Dice Task was performed in an Eastern
European population for the first time, an unexpected finding was observed: CG seemed to favor risky
decisions. Our results indicate that there is no statistically significant difference in executive functions,
psychomotor speed and decision-making under risk between CLBP patients and healthy older adults.
A risky decision-making pattern found in Lithuanian population underscores the importance of cultural
context when examining executive function.
263
THE IMPACT OF NEUROPSYCHOLOGICAL FUNCTIONING ON CHRONIC PAIN: EVIDENCE
FROM A PROSPECTIVE SURGICAL COHORT
1,2
1
1,2,3
N. Attal , A. Masselin-Dubois , V. Martinez
1,2
Baudic
4
4
5
1,2
, C. Jayr , A. Albi , J. Fermanian , D. Bouhassira , S.
1
INSERM U-987, CHU Ambroise Paré, GH Paris Ile de France Ouest, APHP, Boulogne-Billancourt,
3
Université Versailles-Saint Quentin, Versailles, Service d'Anesthésie-Réanimation Chirurgicale,
4
CHU Raymond Poincaré, GH Paris Ile de France Ouest, APHP, Garches, Service de Chirurgie
5
Générale, Hôpital René Huguenin-Institut Curie, Saint Cloud, Service de Biostatistiques, CHU
Necker, APHP, Paris, France
2
Background: It is well established that chronic pain impairs cognition. However, the role of cognitive
functions in the development of chronic pain has not been explored.
Methods: In this prospective longitudinal study, we investigated the role of neuropsychological
functioning in the development of chronic pain, its severity and neuropathic symptoms (DN4
questionnaire), six and 12 months after surgery (total knee arthroplasty for osteoarthritis or breast
surgery for cancer). Neuropsychological tests included the Trail-Making Test (TMT) A and B, and the
Rey-Osterrieth Complex Figure (ROCF) copy and immediate recall, which assess cognitive flexibility,
visuo-spatial processing and visual memory. Anxiety, depression and coping strategies were also
evaluated.
Results: A total of 189 patients were enrolled. Multivariate logistic regression indicated that the
presence of clinical meaningful pain at 6 and 12 months was predicted by poorer cognitive
performance in the TMT B, ROCF-copy (p < 0.01 for pain at 6 months ; p < 0.05 for pain at 12
months) and ROCF- recall (p < 0.01 for pain at 12 months), independently of affective variables.
Linear regression analyses indicated that TMT B and ROCF-immediate recall scores were predictive
of pain intensity (p < 0.01) and neuropathic symptoms (p < 0.05). Results were not affected by the
type of surgery or presurgical pain.
Conclusion: These findings support for the first time the notion that premorbid limited cognitive
flexibility and memory capacities may be involved in the mechanisms of pain chronicity, including its
neuropathic quality.
264
BEYOND THE SOMATOTOPIC ORGANISATION OF PAIN: EVIDENCE FOR A PERIPERSONAL
FRAME OF REFERENCE DURING THE LOCALISATION OF NOCICEPTIVE STIMULI
1
1,2
1
A. De Paepe , V. Legrain , G. Crombez
1
2
Experimental Clinical and Health Psychology, University of Ghent, Ghent, Institute of Neuroscience,
Université Catholique de Louvain, Louvain-la-Neuve, Belgium
Background and aims: In this study we investigated whether nociceptive stimuli are mapped
according a peripersonal frame of reference, taking into account the occurrence of visual cues in
external space and the position of the body parts in external space.
Methods: Using a temporal order judgment task (TOJ), participants had to judge which of two
nociceptive stimuli applied to either hand was perceived in priority. Nociceptive targets were preceded
by visual cues presented either unilaterally or bilaterally. Participants' hands were either in an
uncrossed or a crossed posture. If nociceptive stimuli are mapped according a peripersonal frame of
reference, perception of the nociceptive targets would be biased in favor of the target applied to the
hand positioned at the cued side of space.
Results: The occurrence of an unilateral visual cue effectively biased the perception of nociceptive
stimuli applied to the closest hand independently of the hand position. In other words, processing
priority was given to the nociceptive stimuli applied to the hand positioned at the same side of external
space as the visual cue.
Conclusions: The results of this study demonstrate that nociceptive stimuli are mapped according to
a frame a reference integrating the space of the body and proximal external space. Together with
previous studies, this study provides evidence for the existence of a peripersonal frame of reference
for the mapping of nociceptive stimuli.
265
ASSESSMENT OF THE COGNITIVE DISTORTION OF PAIN IN PATIENTS WITH CHRONIC
TEMPOROMANDIBULAR DISORDERS USING QUANTITATIVE SENSORY TESTING
S. Ishigaki, S. Fukuda, H. Yatani
Department of Fixed Prosthodontics, Osaka University Graduate School of Dentistry, Suita, Japan
Introduction: The aim of this study was to evaluate the cognitive distortion of pain in patients with
chronic temporomandibular disorders (TMD).
Subjects and methods: Subjects consisted of 20 healthy female volunteers (mean age 42.1 ± 7.3
years) and 20 female TMD patients with chronic orofacial pain (mean age 45.3 ± 15.2 years). Heat
stimuli were applied to the skin surface of right mandibular nerve area (V3) and right forearm (FA)
using a thermal sensory stimulator (PATHWAY, Medoc). Each subject underwent the randomly
assigned ten heat stimuli (two sets of five levels of heat stimuli at 0.5 °C intervals) and scored the
subjective pain intensity using visual analogue scale after each stimulus. To evaluate the relationship
between levels of heat stimuli and subjective pain intensities, Person's correlation coefficient was
calculated.
Results: The correlation coefficients between the intensity of heat stimuli and subjective pain score
were: 1) r = .673 (P < .001) in FA and r = .476 (P = .001) in V3 in healthy subjects; and 2) r = .324 (P
= .001) in FA and r = .305 (P = .001) in V3 in TMD patients.
Conclusion: Healthy subjects showed a stronger correlation between the intensity of heat stimuli and
the subjective pain intensities than TMD patients, suggesting that the patients are inferior in
recognizing the intensity of nociceptive stimulus. It was suggested that the QST can be used not only
to evaluate the sensory threshold but also to evaluate the integrity of the pain processing or
recognition system.
266
PLACEBO EFFECTS IN CHRONIC PAIN PATIENTS AND THE ROLE OF EXPERIENCE WITH
MEDICATION
1
1
1
1
2
3
S. Kamping , M. Mueller , H. Saliger , C. Meyer , R. Klinger , J. Benrath , H. Flor
1
1
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health; Medical
2
Faculty Mannheim, Heidelberg University, Mannheim, Psychotherapeutic Outpatient Clinic Behavior
3
Therapy, Department of Psychology, University of Hamburg, Hamburg, Clinic of Anaesthesia and
Intensive Care Medicine, Centre of Pain Therapy, Medical Faculty Mannheim, Heidelberg University,
Mannheim, Germany
Background: In recent years placebo analgesia has often been examined in healthy controls.
However, research in patients is rare though they might be more prone to placebo effects and react
differently to classical conditioning (Klinger et al. (2007), Pain: 128: 31-39). More importantly, the
influence of experience with medication may play a major role.
Methods: We examined 41 patients with chronic pain (mean age 56.70 years +/- 14.54). Subjective
pain ratings to pressure pain stimuli to the right thenar were measured before and after a
pharmacological placebo intervention. Patients received the verbal suggestion (VS) of a potent pain
relieving drug and half of the patients additionally received a conditioning procedure (VS+CC). Prior
experience with medication was also measured. Patients kept a pain diary for 14 days and
participated in a 3 month follow-up.
Results: Both groups showed a significant reduction of experimental (F(1,1) = 8.31; p = 0.007) and
habitual pain ratings (F(1,1) = 153.89; p < 0.001) after placebo intervention. However, there was no
difference in the magnitude of the placebo response between VS and VS+CC. Patients who indicated
that their previous experience with medication was positive (i.e. more effective), showed a larger pain
reduction (p < 0.033).
Conclusions: Chronic pain patients displayed a large placebo effect, with the reduction of habitual
pain being larger than the reduction of experimental pain. Importantly, previous experience with
medication seems to play a large role in the formation of the placebo response.
Supported by: the Deutsche Forschungsgemeinschaft (grant Fl156/33-1 to HF).
267
SELECTIVE RECALL IN CLBP PATIENTS IS ASSOCIATED WITH FEAR- AVOIDANCE AND
ENDURANCE PAIN RESPONSES
Z. Karimi, A. Pilenko, M.I. Hasenbring
Department of Medical Psychology and Medical Sociology, Ruhr-University of Bochum, Faculty of
Medicine, Bochum, Germany
Background and aim: Selective memory for pain related material is a potential cognitive mechanism
in the maintenance of chronic low back pain (CLBP). Based on the Avoidance-Endurance Model of
pain the present study sought to investigate the relationship between CLBP patients' pain related
single responses as well as response pattern and their memory bias. Fear-Avoidance responses
(FAR) and Endurance Responses (ER) are assumed to be positively associated with recall of pain
words. Based on different pathways, patients with FAR and ER pattern are expected to recall more
pain words than patients with an Adaptive Response (AR) pattern.
Methods: 31 CLBP patients were tested on a free recall task comprising (affective and sensory) pain
words and neutral words. By means of correlational analysis associations between recall and single
responses were assessed. The Avoidance Endurance Questionnaire was used to classify patients in
subgroups with FAR-, ER-, and AR pattern. Repeated measure of analysis of variance was performed
to compare recall of pain words and neutral words as a function of response pattern.
Results: FAR single responses were negatively correlated with recall of pain words and positively
correlated with recall of neutral words. For ER, negative correlations were found for affective pain
words. Subgroups of patients representing ER pattern recalled more pain words than neutral words.
In contrast, patients with FAR pattern recalled more neutral than pain words.
Conclusion: Memory biases in CLBP patients are related to their response pattern to pain. The
results emphasize the importance of individualized risk based cognitive-behavioural interventions.
268
QUALITY OF QUANTITATIVE RESEARCH AMONG OLDER POPULATIONS - RELIABILITY OF
RESPONSIVENESS REGARDING THE INFLUENCE OF AGE AND COGNITIVE IMPAIRMENT
P. Kutschar, N. Schuessler, J. Osterbrink
Institute of Nursing Science and Practice, Paracelsus Medical University, Salzburg, Austria
Recently, there has been a growing engagement in understanding the abilities of cognitively impaired
elderly regarding the inclusion in survey research. It is argued that individuals' ability to respond to
survey questions is highly moderated by their status of cognitive function. Mainly due to limited means
in retrieval of information and comprehension, growing portions of item-nonresponse [INR] are to be
expected.
As an explorative secondary analysis, different dimensions of the relations between age, cognitive
impairment and INR are examined. The used data regarding nursing home residents come from the
large health services research study ´Action Alliance Pain-free City Muenster´. Residents with no/mild
impairments [Mini-Mental State Examination (MMSE): 18-30, n=225] were interviewed with
questionnaires and residents with moderate impairments [MMSE: 10-17, n=61] were examined using
both self-report as well as proxy assessment.
To measure the influence of age and cognitive impairment, correlations, regression analyses and ttests are used. Results support the thesis, that increasing age and decreasing cognitive functions
increase the probability of item-nonresponse. For example, statistically highly significant effects of age
[rho=0.241] and MMSE-score [rho=-0.301] on item-nonresponse proportions are observed.
Furthermore, t-test indicates a highly significant mean difference of 8.7 percentage points between
residents with no/mild [INR-mean=3.9%] and residents with moderate [INR-mean=12.6%] cognitive
impairments.
Methodological considerations and empirical results support the need for a ´general theory´ of the
question-/answer-process for cognitively impaired elderly to understand underlying informationprocessing logics. Sophisticated research is needed in order to avoid a systematic exclusion of
persons with cognitive impairments from research and societal decision-making.
269
THE EFFECTS OF LIVING WITH CHRONIC PAIN ON PATIENTS AND THEIR MAIN FAMILY
CAREGIVERS
1
2
1
S. Mohammadi , M. Dehghani , R. Sanderman , M. Hagedoorn
1
1
Department of Health Sciences University Medical Center Groningen, University of Groningen,
2
Groningen, The Netherlands, Family Research Institute, Shahid Beheshti University, Tehran, Iran
Background and aims: Chronic pain patients (CPPs) and their family caregivers (CGs) form an
interactive system meaning that they simultaneously affect each other's pain-related cognitions and
responses. This study aims to provide evidence regarding associations of pain-related cognitions and
affect between CPPs and CGs and to examine the role of these variables in CPPs' functional
disability.
Methods: A total of 124 CPPs and their CGs who were referred to the Orthopedic center of Atieh
Hospital (Tehran, Iran) agreed to participate. They both completed visual analogue scales (VAS) to
assess pain, the Tampa Scale of Kinesiophobia (TSK) to assess fear of movement, and the pain
behavior checklist (PBCL) to evaluate pain behaviors. They filled out the PCQ which measures pain
catastrophizing, and with the DASS-21 depression and anxiety and stress was assessed. To assess
functional disability CPPs answered the pain disability questionnaire (PDQ).
Results: Correlation analyses showed moderate agreement between CPPs and CGs' estimation of
present pain (0.47**), previous pain (0.35**), future pain (0.25**), and pain-related behaviors (0.57**).
There were also significant correlations between CPPs and CGs helplessness (0.24**), their anxiety
(0.23*) and depression (0.27**). Hierarchical regression analysis indicated that patients' fear of
movement and intensity of present pain, and caregivers' helplessness predict CPPs' functional
r 2
disability ( R =0.32).
Conclusions: The findings support the idea of an interactive system in which CPPs and CGs
cognitions and affects are related. Also CGs' pain-related beliefs seems to interfere with CPPs'
disability level. This emphasizes the importance of involving the caregiver in pain interventions
programs.
270
PSYCHOLOGICAL PREDICTORS OF RESPONDERS AND NON-RESPONDERS TO THE
THERMAL GRILL ILLUSION
1
2
1
R. Scheuren , S. Sütterlin , F. Anton
1
2
Laboratory of Psychobiology and Neurophysiology (LPN), Research Unit INSIDE, Research Unit
INSIDE, University of Luxembourg, Luxembourg, Luxembourg
Background and aims: Interposed non-noxious cold and warm cutaneous stimuli applied via a
thermal grill have repeatedly been shown to generate a paradoxical pain sensation, also described as
'thermal grill illusion of pain'. While the inherent physiological mechanisms are largely understood,
psychological and psychophysiological determinants still have to be uncovered, particularly since a
significant part of the tested subjects does not display thermal grill-induced pain. The aim of the
present study was to investigate whether different personality traits constitute predictors for the
separation of responders and non-responders.
Methods: A total sample of 54 healthy students participated in the study. Prior to the experiment, the
subjects completed a series of trait- and state-related questionnaires. Paradoxical pain was elicited
with a custom-built, water-bath driven thermal grill device. The temperatures of the interlaced five cold
and five warm bars were set at 15°C and 41°C. Participants kept the palm of their dominant hand on
the thermal grill for one minute and rated their pain perceptions every 15 seconds on a numerical
rating scale (NRS; 0-100).
Results: A group of responders (N=29) and one of non-responders (N=25) to the grill illusion could
be distinguished. Among other psychological factors, trait rumination was identified as a major
predictor of the perceived paradoxical pain intensity (p = .008) in the thermal grill responders.
Conclusion: Our findings corroborate the hypotheses of an involvement of personality traits in the
thermal grill pain percept.
271
PAIN-RELATED COGNITIVE INTERFERENCE IS MORE PRONOUNCED FOR TRIGEMINAL PAIN
THAN FOR PERIPHERAL PAIN
K. Schmidt, C. Sinke, U. Bingel
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Background and aims: Pain captures attention and interferes with ongoing cognitive processes such
as memory performance or learning. This phenomenon has been termed the interruptive function of
pain. Here we investigated the interruptive function of pain applied to the trigeminal system compared
to pain applied to extremities. Based on the unique relevance of the facial peripersonal space we
hypothesized that nociceptive stimuli near or in the face have a stronger interruptive capacity
compared to pain outside the face.
Methods: 25 healthy participants (11 male, age M±SD: 25.96±4.31) received electric painful
stimulation on the forehead, the dorsum of the hand and foot while performing a rapid serial visual
performance task. The task was either presented alone or with electrical pain. The percentage of
correct responses and the inverse efficiency were calculated as outcome variables.
Results: Correct responses were significantly lower in the pain condition compared to the control
condition in all three body sites. Importantly, although pain intensities were perceived as equally
painful in all pain conditions, the number of correct responses was significantly lower in the trigeminal
pain condition compared to the hand and foot conditions. Inverse efficiency results slightly failed
significance but indicated a similar pattern with strongest task impairment for trigeminal pain.
Conclusions: These results suggest a higher impairment of cognitive functions by painful trigeminal
stimulation compared to pain outside the face. We believe that this finding holds important clinical
implications regarding the functional impairment often observed in patients suffering from chronic
headache syndromes.
272
AWARENESS OF SPACE MEDIATES CROSSED-HANDS ANALGESIA
1,2
1
3
3
4
D. Torta , V. Vizzari , S. Barba , P. Gindri , P. Cerrato , G. Geminiani
1
2
1
3
Department of Psychology, University of Turin, CCS Complex System Unit, Koelliker Hospital, San
4
Camillo Hospital, Stroke Unit, Città della Salute e della Scienza, Turin, Italy
Background: Crossed-hands analgesia (CHA), phenomenon for which noxious stimuli applied to the
hands crossed over the body midline are perceived as less intense, is mediated by multimodal
associative areas such as the posterior parietal cortex (PPC) (1,2). The PPC (especially the right
PPC) participates in the representation of peripersonal space and, if damaged, can lead to spatial
neglect. Here, we investigated if representation of contralesional space is crucial to the emerge of
CHA.
Methods: 18 right brain-damaged patients without primary sensory deficits were recruited for this
study. Patients were tested for the presence of neglect or extinction by means of an accurate
neuropsychological battery. 10 patients were diagnosed with neglect or extinction (N+/E+), 8 without
(N-/E-). Patients received mechanical painful stimuli of two intensities on their hands, while these
were kept either uncrossed or crossed over the body midline. Vision of the hands was precluded.
Patients were asked to rate the intensity of each stimulus.
Results: Both groups could distinguish the intensity of the stimuli, as evidenced by higher ratings
attributed to more intense stimuli (N+/E+ p=0.010; N-/E- p=0.08). This suggests that stimuli were
properly felt. Right brain damaged patients without neglect or extinction perceived stimuli as less
intense when the hands were crossed (p=0.015). Conversely, no such an effect was observed in
patients with neglect or extinction (p=0.332).
Conclusion: Awareness of contralesional space is crucial for the emergence of CHA. These data
provide important inputs on how the representation of peripersonal space shapes pain perception.
273
ANTICIPATION OF PAIN AT ONE SIDE OF THE JAW PRIORITIZES TACTILE STIMULI AT THAT
SIDE
C. Vanden Bulcke, S. Van Damme, G. Crombez
Experimental-Clinical and Health Psychology, Ghent University, Ghent, Belgium
Background/aims: Attention is a central concept in theories on pain perception and pain-related
disability. This study investigated if anticipating pain in a particular region of the body may result in the
attentional prioritization of innocuous somatosensory stimuli at the threatened location.
Methods: Undergraduate students (N = 19) performed a tactile Temporal Order Judgment (TOJ)
task. They indicated which one of two tactile stimuli, one administered to each side of the jaw at a
range of different stimulus onset asynchronies (SOA), was perceived first. Each trial was preceded by
a cue (one of two colors) indicating whether or not painful stimulation on one jaw could possibly follow
(threat versus neutral trials).
Results: Based on the proportion of correct responses per SOA, the PSS (point of subjective
simultaneity), assessing biases in spatial attention to the threatened location, was calculated. The
PSS was significantly larger in threat trials (M=24.83ms, SD=22.16) than in neutral trials (M=10.56ms,
SD=16.26), F(1,17) = 8.97, p < 0.01.
Conclusion: The findings demonstrated that the anticipation of pain at a particular location of the
body resulted in the attentional prioritization of innocuous tactile stimuli at that location, indicating
biased somatosensory attention towards the threatened body location. The tactile TOJ appears to be
a promising tool to investigate if persons with chronic pain resulting from, for example,
temporomandibular joint dysfunction, are characterized by hypervigilance, i.e., an excessive focus of
attention to, somatosensory signals in the affected body part.
Acknowledgements/disclosures: This research is supported by the Research Foundation Flanders
(FWO Vlaanderen) (B/11734/02).
274
SYMPTOMS OF ANXIETY, DEPRESSION AND THEIR INTERFERENCE IN DAILY LIVING OF
PATIENTS WITH CHRONIC PAIN
1
2
3
3
1
É.B.D.M. Vieira , C.B. da Silva , J.B.S. Garcia , A.B. Carvalho , K.A. de Albuquerque , J.Y. Matuoka
1
2
1
3
Nursing School, São Paulo University, Nursing, CEST, Medicine, Federal University of Maranhão UFMA, São Luís, Brazil
Background and aims: To determine the prevalence and correlation between anxiety, depression,
pain intensity and their implications for lives of patients with chronic pain.
Methods: Cross-sectional study conducted in 2012 with chronic pain patients. Anxiety and
depression were assessed by the Hospital Anxiety and Depression Scale for Patients with Chronic
Pain (HADS), and pain interference in daily life by the Brief Pain Inventory (BPI). Spearman
correlations were calculated.
Results: Most patients were female (77.5%), mean age of 48.1y (SD = 7.7), 8 y of schooling (42.5%)
and Caucasian (70%). About 45% were out of work because of their pain and 47.5% conceptualized
reported the current health status as fair. Daily pain reached 72.5%, with a mean intensity of 7.5 (SD
= 2.0). The greatest impediments caused by pain were to work (52.7%) and activities of daily living
(37.5%). Symptoms of anxiety were observed in 75% and of depression in 67.5%. Out of these,
88.8% had anxiety and depression simultaneously. According to BPI items, anxiety and depression
were positively correlated (p < 0.05) with higher pain intensity (r=0.35; r= 0.41), lower degree of
general activity (r=0.46; r=0.54), mood (r=0.46; r=0.60), walking ability (r=0.35; r=0.37), work (r=0.47;
r=0.53), relationships with other people (r=0.35; r=0.31), sleep (r=0.44; r=0.37) and ability to enjoy life
(r=0.44; r=0.44).
Conclusion: The prevalence of anxiety and depression was high and had a negative impact on
general activities, mood, interpersonal relationships, mobility, exercise, sleep, and enjoyment of life.
275
HOW PAINFUL WAS IT? RETROSPECTIVE OVERESTIMATION OF PAIN IN HIGH HABITUAL
SYMPTOM REPORTERS
1
2
1
M. Walentynowicz , A.-M. Verlinden , I. Van Diest , O. Van den Bergh
1
1
2
Department of Psychology, Research Group on Health Psychology, Department of Psychology,
University of Leuven, Leuven, Belgium
Background and aims: Elevated but unfounded symptom reporting is strongly associated with trait
negative affectivity (NA). We selected high and low habitual symptom reporters (scoring high and low
for NA, respectively) and investigated retrospective reporting of pain. During a retrospective
evaluation of a painful event, the initial somatic experience is dynamically reconstructed and
susceptible to various distortions. We hypothesized that high symptom reporters (HSR) would show
more distorted memory for pain than low symptom reporters (LSR).
Methods: Healthy female students (N = 31; 13 HSR/18 LSR) participated in a cold pressor task. In a
short trial, they submerged one hand in water at 12°C for 60s. In a long trial, they held their other
hand in water at 12°C for 60s, with additional 60s in water at 14°C. The order of the two trials was
counterbalanced across participants and groups. Pain ratings were collected at four times:
(1) continuously during pain induction,
(2) after each trial,
(3) after the experiment,
(4) after 2 weeks.
Results: Continuous pain ratings during hand immersion were not different for both groups. However,
significantly higher retrospective pain assessments were given by HSR compared to LSR, starting
already at the first retrospective evaluation, i.e. right after the trial.
Conclusions: These preliminary findings suggest that retrospective pain ratings are importantly
biased in HSR. Pain overestimation in this group occurs directly after completion of the trial, showing
that distortions in symptom memory may operate promptly.
276
THE PROGNOSTIC VALUE OF CATASTROPHIZING AND FEAR AVOIDANCE BELIEFS IN
PATIENTS WITH LOW BACK PAIN: SUMMARY OF TWO SYSTEMATIC REVIEWS
1
2
3,4
S. Weiser , U. Held , E. Rassmussen-Barr , M.M. Wertli
1
5,6
2
Orthopaedics, New York University, New York, NY, USA, University Hospital Zurich, Zurich,
3
4
Switzerland, New York University Langone Medical Center, New York, NY, USA, Karolinska
5
Institutet, Stockholm, Sweden, University of Zurich and Balgrist University Hospital, Zurich,
6
Switzerland, New York University, New York, NY, USA
Background and aims: Ear avoidance beliefs (FAB) and catastrophizing have been shown to predict
outcome in patients with low back pain (LBP), though their relative value is unknown.
Methods: Two systematic reviews were conducted to assesses the prognostic value of these factors
for commonly assessed outcomes.MethodsBIOSIS, CINAHL, Cochrane Library, Embase, OTSeeker,
PeDRO, PsycInfo, Medline, Scopus, and Web of Science databases were searched. Observational
studies with 100 and more patients and follow-up of at least three months were included. Excluded
were studies of poor methodological quality.
Results: In the first systematic review, FAB were assessed. From 2031 references, 53 were retained.
After the full text was assessed, 21 were included. When catastrophizing was investigated in the
second systematic review, 1473 references were retrieved and 77 were retained. After the full text
was assessed 16 studies were included. FAB were prognostic in subacute patients with LBP for workrelated outcomes only. The findings for catastrophizing showed no clear relationship of the variable to
work outcomes. However, catastrophizing was associated with pain and disability in patients with LBP
of all stages.
Conclusions: The results of 2 systematic reviews suggest that both FAB and catastrophizing are
predictive of outcome in patients with LBP, though they are distinct in the specific outcomes they are
associated with. These findings are limited in that few studies investigated both factors
simultaneously.
615
ABSTRACT SUBMISSION: SUBJECTIVE REPORTS OF COGNITIVE DYSFUNCTION AMONG
PATIENTS SUFFERING FROM COMPLEX SYMPTOM DISORDERS: THE EVERYDAY MEMORY
QUESTIONNAIRE-REVISED
1,2
2,3
1,2
J.K. Aasvik , A. Woodhouse , P. Borchgrevink , N.I. Landrø
4,5
1
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology,
3
National Competence Centre for Complex Symptom Disorders, Department of Public Health and
4
General Practice, Norwegian University of Science and Technology, National Competence Centre for
5
Complex Symptom Disorders, St Olavs Hospital, Trondheim University Hospital, Centre for the Study
of Human Cognition Department of Psychology, University of Oslo Norway, Trondheim, Norway
2
Background and aims: Patients with symptoms of pain, fatigue, sleep disorders and common mental
disorders (depression and anxiety) frequently report cognitive dysfunction, specifically with attention
and memory. Cognitive dysfunction can be considered a functional limiting symptom dimension
causing major obstacles to daily activities like work and social interaction.
Memory complaints have generally been attributed to depressive symptoms. A recent study with
chronic pain patients linked cognitive complaints to objective test performance, independently of
depressive symptoms. This suggests that cognitive complaints reflect actual impairment, not
depressed mind.
This study aimed to examine prevalence rates of memory complaints among patients with complex
symptom disorders. We also wanted to examine how different complex symptoms influence memory
complaints.
Methods: In a cross-sectional study, self-assessments of everyday memory dysfunction were
sampled using The Everyday Memory Questionnaire-Revised (EMQ). Subjects were 165 patients with
complex symptom disorders, referred to a vocational rehabilitation program in Norway. Logistic
regression analysis was performed using a dichotomized EMQ as the outcome variable. Independent
variables included pain, fatigue, depression, sleep-disturbances, anxiety, age, gender and level of
education.
Results: 20 % of the subjects report clinically significant memory problems. The results show a strong
association between symptoms of fatigue (OR 5, 24) and anxiety (OR 4, 17) with memory complaints.
Associations with depression, pain and other factors were not statistically significant.
Conclusions: 20 % of the subjects report significant memory problems. Complaints of memory
impairment among patients with complex symptom disorders were associated with symptoms of
fatigue and anxiety in this study.
616
THE PREDICTING ROLE OF SPOUSE PAIN CATASROPHIZING ON REPORT OF MARITAL
SATISFACTION IN CHRONIC PAIN PATIENT AND THEIR SPOUSES
F. Akbari, M. Dehghani, M. Habibi, N. Esmaeilian, V. Naghavi
Shahid Beheshti University, Tehran, Iran
Background and aims: People with chronic pain suffer from a host of problems including cognitive
distortions, psychological distress and family problems. Chronic pain has adverse effects on
individuals with chronic pain (ICPs) as well as their spouses. In other words, they may affect each
other's pain-related cognitions and responses. So, the current study investigates the role of spouse
pain catasrophizing in prediction of marital satisfaction in patients and their spouses.
Methods: A total of 80 CPPs and their spouses participated in this research. They were referred to
the orthopedic clinic center of Atieh Hospital. They completed the Pain Catasrophizing Questionnaire
(PCQ) and Marital Adjustment Test (MAT).
Results: Correlation analyses showed significant correlations between spouse ruminations about
*
pain and marital satisfaction of patient (0/25 ). Also there were no significant correlations between
magnification and helplessness of spouse and patient´s marital satisfaction. Regression analysis
2
indicated that spouse catasrophizing predicts both patient and spouse marital satisfaction (R = 0/31).
Conclusions: The findings of this research supports the hypothesis that spouse pain related
rumination predicts the patients marital dissatisfaction suggesting that targeting improvement in
spouse beliefs might be an important aspect of improvement of marital relations among patients with
chronic pain and their spouses.
617
SPOUSES OF PAIN PATIENTS SHOW SIMILAR SELECTIVE ATTENTION PATTERNS TO PAINRELATED STIMULI
M. Enjedani, M. Dehghani, M. Heidari
Shahid Beheshti University, Tehran, Iran
Background and aims: Many researchers have shown that patients with chronic pain selectively
attend to pain-related stimuli. in addition, a recent study found that main care giver the patients shows
similar biases towards pain stimuli However, it has not been investigated yet whether spouses of pain
patients have selective attention to pain information.
Methods: As such, the objective this research is to investigate cognitive biases to painful or happy
faces in patients and their partners. Chronic pain patients who attend hospital with their spouses were
requested to participate in the research. Inclusion criteria for the pain group were, having constant
pain for more than 3 months, sufficient literacy to complete questionnaires, and able to use both
hands for completing a computerized test. As sample of 50 chronic musculoskeletal pain patients and
their spouses 50 dyad. and, 30 persons that neither had chronic pain nor living with a chronic pain
patient as control group collected. All groups completed a pictorial dot-probe task.
Results: Analyses found no significant difference between patients and their spouses on selective
attention to pain related stimuli but these two groups were significantly different from control group.
There was not any significant difference between groups on selective attention to happy related
stimuli.
Conclusions: According to the results of current research, living with a chronic musculoskeletal pain
patient may contribute to developmental similar cognitive biases toward pain related stimuli in their
spouses.
618
ASSOCIATIONS OF PREOPERATIVE DISPOSITIONAL AND SITUATIONAL PAIN
CATASTROPHIZING WITH RESPONSES TO POSTOPERATIVE PAIN: A PROSPECTIVE
COHORT STUDY
1
2
1
3
K. Grosen , A.M. Drewes , H.K. Pilegaard , M. Pfeiffer-Jensen , L. Vase
1
4,5
2
Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, MechSense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg
3
4
Hospital, Aalborg, Department of Rheumatology, Aarhus University Hospital, Department of
5
Psychology and Behavioural Sciences, Aarhus University, Danish Pain Research Center, Aarhus
University Hospital, Aarhus, Denmark
Background and aims: Previous studies have found measures of situational pain catastrophizing
(i.e. catastrophizing measured directly after exposure to a noxious stimulation) to be a better predictor
of experimental pain responses than dispositional measures (i.e. recall of catastrophizing during
previous occurrences of pain). However, the properties of these two different forms of pain-related
catastrophizing remain unclear. The aim of this study was to evaluate both dispositional and
situational catastrophizing in patients undergoing elective thoracic surgery.
Methods: Preoperatively, 42 patients scheduled for funnel chest surgery completed the State-Trait
Anxiety Inventory, Beck's Depression Inventory, and Pain Catastrophizing Scale (PCS) before
undergoing pressure algometry and a cold pressor test (CPT). PCS was re-administered following
CPT and patients were instructed to reference the cold pressor pain while answering (situational
PCS). Regression analysis was used to test if dispositional and situational PCS significantly predicted
experimental pain, clinical postoperative pain at rest (PAR) and movement-evoked pain (MEP).
Results: Dispositional PCS predicted only pressure pain thresholds (β=-11.2, p=0.01). CPT pain
(β=3.32, p=0.001) and pressure pain tolerance (β=-0.01, p=0.02) predicted situational PCS. We
observed a borderline significant relationship between situational PCS and PAR (β=0.05, p=0.06),
whereas situational PCS significantly predicted MEP (β=0.06, p=0.03). The effects of situational PCS
on postoperative pain-related outcomes remained unchanged when statistically controlled for anxiety,
depression, and CPT sensitivity.
Conclusions: These findings indicate that preoperative situational pain catastrophizing predicts
postoperative pain intensity and highlight situational pain catastrophizing as a unique construct apart
from the referenced noxious stimulation itself.
619
SHIFTING ATTENTION BETWEEN THE SPACE OF THE BODY AND EXTERNAL SPACE.
ELECTROPHYSIOLOGICAL CORRELATES OF VISUO-NOCICEPTIVE CROSSMODAL SPATIAL
ATTENTION
V. Legrain, M. Gergelyfi, M. Marky, A. Mouraux
Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
Background and aims: The study tested whether nociceptive stimuli applied to a body limb can
orient spatial attention in external space towards visual stimuli delivered close to that limb. We also
tested whether this crossmodal link depends on a body-based frame of reference (i.e., depends on
which hand is stimulated) or a space-based frame of reference (i.e., depends on where in space is the
stimulated hand).
Methods: Participants were instructed to detect occasional targets in series of visual stimuli
presented close to either the left hand or the right hand. Each visual stimulus was preceded by a
nociceptive stimulus applied either to the left or right hand. In one half of the trials, the location of the
hand on which was applied the nociceptive stimulus and the location of the visual stimulus were
congruent (i.e., same side of space), in the other half they were incongruent (i.e., opposite side of
space). Participants' hands were either in an uncrossed or a crossed posture.
Results: Visual stimuli elicited cortical activities of greater magnitude, as revealed by event-related
potentials, when the spatial locations of the visual stimulus and the nociceptive cue were congruent.
The effect was independent of the posture (e.g., a left-sided visual stimulus was positively affected by
a nociceptive stimulus applied to the left hand in an uncrossed posture, but to the right hand in a
crossed posture).
Conclusions: This crossmodal interaction suggests the existence of a space-based peripersonal
frame of reference to localize nociceptive stimuli.
620
THE ROLE OF PRIOR EXPERIENCE FOR PLACEBO EFFECTS IN THE TREATMENT OF
CHRONIC BACK PAIN
1
1
2
2
M. Mueller , S. Kamping , J. Schmitz , R. Klinger , H. Flor
1
1
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical
2
Faculty Mannheim, Heidelberg University, Mannheim, Psychotherapeutic Outpatient Clinic Behavior
Therapy, Department of Psychology, University of Hamburg, Hamburg, Germany
Background and aims: Research into placebo analgesia in patients is sparse. There is evidence,
however, that patients may be more prone to placebo effects (Klinger et al., 2007, Pain: 128(1-2): 3139). We investigated how prior experience and attitude modulated placebo effects in chronic back
pain patients with respect to pain perception, functional capacity and underlying neurobiological
mechanisms.
Methods: In this ongoing study, 19 chronic back pain patients (mean age 54.05 ±14.25) were
examined. Pain ratings to intra-epidermal electrical stimulation to the lower back were assessed
before and after a pharmacological placebo intervention. All patients received verbal suggestions (VS)
of a potent painkiller, while half of the participants additionally underwent a classical conditioning
procedure (VS+CC). Cortical activity was examined on day 1, maintenance of effects on day 7.
Patients performed behavioral exercises to investigate effects on functional capacity.
Results: Both groups showed reduced experimental (F(1,15)=7.77, p=.014) and habitual pain
(F(1,15)=20.83, p< .001) after the placebo, with more pronounced effects on day 7. Functional
capacity improved (F(1,13)=8.46, p=.012). Increased frontal and striatal activation was observed
during placebo. No differential effects have been found for VS and VS+CC. Increased hippocampal
activity was associated with positive attitudes towards analgesic medication.
Conclusions: A placebo intervention led to reduced pain and improved functional capacity in chronic
back pain patients. Neural activity underlying placebo analgesia seems to differ from those of healthy
controls, possibly indicating a different mechanism. Attitude influences brain activation during
placebo.
Supported by: Deutsche Forschungsgemeinschaft (grant Fl156/33-1 to HF within research unit FOR
1328).
621
EFFECT OF EXPERIMENTAL PAIN ON THE ACQUISITION AND RETENTION OF A
LOCOMOTOR ADAPTATION TASK
1,2
1,2
1,2
J. Bouffard , J.-S. Roy , L. Bouyer , C. Mercier
1,2
1
Centre for Interdisciplinary Research in Rehabilitation and Social Integration (CIRRIS),
Rehabilitation Department, Laval University, Quebec, QC, Canada
2
Background and aims: It is well established that pain can influence motor control, but its influence
on our ability to learn new motor tasks remains unclear.
The aim of this study was to evaluate the effect of experimental pain on the acquisition and retention
of a locomotor adaptation task.
Methods: Healthy subjects (n=21) walked on a treadmill on two consecutive days. Each day, a force
perturbation was applied at their ankle during walking. To adapt, subjects had to learn to modify their
motor commands in order to minimize movement errors caused by the perturbation. On day 1,
subjects performed the task either without (n=12) or with pain ((n=9) induced by applying capsaicin
cream [1%] around the ankle (NRS peak pain intensity of 5.4/10±1.9). All subjects performed a
retention test without pain 24 hours later. The mean absolute error during swing was calculated by
comparing ankle joint angles before, during, and after exposure to the force perturbation. Two-way
ANOVAs (early vs. late adaptation / Pain vs. No Pain) were performed to compare the evolution of
error between groups on each day.
Results: On day 1, only a main effect of time was found showing a performance improvement with
training in both groups, without any effect of the presence of pain. However, a main effect of group
was found during the retention test, revealing that the pain group performed poorer than the control
group.
Conclusion: Experimental pain decreases retention of locomotor adaptation even though
performance during initial acquisition appeared unaffected by pain.
622
LEVELS OF HEALTH LITERACY IN PATIENTS WITH CHRONIC PAIN: A CROSS-SECTIONAL
SURVEY
1
1
B.M. Fullen , E.G. Creighton , C.K. Power
2
1
School of Public Health, Physiotherapy and Population Science, University College Dublin,
Anaesthesia and Pain Medicine, Tallaght Hospital, Dublin, Ireland
2
Background and aims: Health Literacy (HL) encompasses a person's motivation and competences
to access, understand, appraise and apply health information, to maintain or improve their quality of
life (Sorenson et al 2012). Low HL is linked to undesirable health behaviours and outcomes in chronic
conditions including pain (Briggs et al 2011). This study aims to establish the level of HL amongst
patients with chronic pain and determine the impact of demographic variables on these scores.
Methods: Patients were recruited from an outpatient pain clinic. Participants completed a
demographic form and the New Vital Sign (NVS) HL questionnaire (Weiss et al 2004). The NVS
scores range from 0-6 (0-1=high likelihood of limited HL, 2-3=possibility of limited HL and a score of 46=adequate HL. Health literacy scores and demographic variables were analysed for significant
relationships.
Results: Of 65 patients recruited, 50 (77%) had a high likelihood or possibility of limited HL. Over two
thirds of these patients (68%, n=26) only completed primary school or junior certificate level of
education. Patients with high likelihood of limited HL were significantly older than those with a
possibility of limited HL (p=0.03), or adequate literacy (p=0.01).
Conclusion: The prevalence rate of inadequate HL among patients with chronic pain is high.
Establishing patient's level of HL is important so as to allow for tailoring of treatment information and
instructions. This will ensure the highest level of care is being provided to vulnerable groups.
623
LEARNING AND MEMORY PROCESSES IN ABDOMINAL PAIN: CONTEXT-DEPENDENT
EFFECTS ON EXTINCTION AND REACTIVATION OF CLASSICALLY-CONDITIONED FEAR
MEMORIES
A. Icenhour, J. Kattoor, S. Hampel, S. Benson, S. Elsenbruch
University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Background: Little is known about associative learning and memory processes in the context of
visceral pain. We recently established a visceral fear conditioning model. Herein, we address the role
of a context change on extinction learning and on context-dependent renewal of previously
extinguished fear memories.
+
Methods: In two groups of healthy subjects, conditioned stimuli (CS ) were paired with painful rectal
distensions as unconditioned stimuli (US), while different stimuli (CS ) were presented without US.
During extinction, all CSs were presented without US. The extinction-context was changed in one
group (ABA) whereas in a control group (AAA), learning and extinction took place in the same
context. Renewal was evaluated in a final phase in which CSs were presented unpaired in the original
+
learning context. The groups were compared with respect to changes in valence ratings to CS and
CS .
+
Results: Following conditioning, both groups revealed a significant increase in CS when compared
to CS unpleasantness. During extinction, the normalization of differential valence ratings was
significantly enhanced in the group with the context change (i.e., ABA group), indicating more
effective extinction. In addition, the return to the original learning context led to a renewal-effect
+
indicated by greater relative CS -aversion in the ABA compared to the AAA group.
Conclusions: This is the first study evaluating the context-dependency of aversive visceral learning
and memory processes in a visceral pain model. These findings support facilitated inhibitory learning
after acquired anticipatory fear and support a reactivation of extinguished fear due to a change of
context.
624
EFFECT OF EXPERIMENTAL PAIN ON ACQUISITION AND RETENTION OF FORCE FIELD
ADAPTATION DURING HUMAN REACHING
1,2
1
1,2
1,2
M. Lamothe , M. Gagné , J.-S. Roy , L.J. Bouyer , C. Mercier
1,2
1
The Centre for Interdisciplinary Research in Rehabilitation and Social Integration (CIRRIS),
Rehabilitation Department, Laval University, Quebec, QC, Canada
2
Background and aims: Pain is one of the most common symptoms following injury, and thus affects
a large proportion of patients receiving motor rehabilitation. However the influence of pain on motor
learning is still unknown. This study assessed the effect of experimental pain on force field (FF)
adaptation during a reaching task and on next day retention.
Methods: Thirty subjects were randomized to either a Control or Pain group (capsaicin cream [1%]).
Subjects made ballistic reaching movements towards two targets on two consecutive days. On Day1,
the task was performed without (baseline) and with FF perturbation (FFd1). On Day2, the task was
only performed with FF (FFd2). Pain (when applicable) was applied only on Day1. On each trial,
endpoint trajectory deviations from a straight line (movement errors) were quantified.Time-courses of
adaptation for each condition were analyzed into ten bins.
Results: Pain had no effect on baseline performance (F=1.94, P=0.175). On Day1, performance
improved across time in both groups (F=17.14, P< 0.001), without any effect of pain. Both groups also
showed retention, as errors in early FFd2 were lower than in early FFd1 (F=40.08, P< 0.001). Again
no effect of pain was observed.
Conclusions: Results suggest that experimental pain does not interfere with acquisition and retention
in a reaching task. Interestingly however, no significant relationship was observed between Day1 and
2
Day2 performance in subjects with pain (P=0.130, R =0.16), while a tight association was observed in
2
control subjects (P< 0.001, R =0.76). This might indicate more variable motor strategies in presence
of pain.
625
CHRONIC PAIN IN A FAMILY CONTEXT: AN ART PROJECT INFORMED BY LIVED
EXPERIENCE
P. Moss
Photography, University of Cumbria, Carlisle, UK
Pain is an entirely subjective experience which we may struggle to articulate and share with others.
Living with chronic pain has devastating effects on patients, but also on relationships and family life.
Artistic representations of pain tend to be reduced to the sufferer´s experience rather than as an
ongoing family strain.
The project aims to portray photographically everyday life of families living with chronic pain in order
to express its effects on patients, spouses, and children and to initiate a shift in perspective of
understanding chronic pain as a phenomenon affecting the social realm around a patient through
visual art rather than clinical analyses of the patient only.
My work is developed on the grounds of semi-structured interviews with four families, each with a
parent suffering from chronic pain. By employing an interpretive phenomenological approach the
participants' lived experience of chronic pain is focused on.
It is important to note that I approach the families as a fellow sufferer rather than analysing chronic
pain from a clinical objectified perspective. This facilitates a particularly positive way of understanding
the individuals' positions within the families traumatised by the ongoing stress of chronic illness.
The translation of these experiences into photographic images entails a rigorous development of a
visual language which is conducted alongside the interview and analysis process. The final images
are aimed to address a general non-academic audience.
The study received ethical approval by the NHS Ethics Panel in Lancaster, UK and should be
completed in October 2014.
626
NORWEGIAN NURSES´ KNOWLEDGE AND ATTITUDES REGARDING PAIN AND PAIN RELIEF
IN CHILDREN
1
2
3
K. Raaum Hovde , T. Høilo Granheim , K.-A. Christophersen , A. Dihle
1
4
2
Oslo University Hospital, Ullevaal, Oslo, Department of Surgery, Akershus University Hospital,
3
4
Lørenskog, Institute of Political Science, University of Oslo, Institute of Nursing and Health,
Diakonhjemmet University College, Oslo, Norway
Background: Pain in children is underestimated and undertreated. Nurses' attitudes and lack of
knowledge are internationally reported as major causes of insufficient treatment of pain.
Objective: To survey Norwegian paediatric nurses' knowledge and attitudes regarding pain in
hospitalized children and adolescents (0-18 years).
Methods: This is a quantitative study with a cross-sectional design. The Pediatric Nurses' Knowledge
and Attitudes Survey Regarding Pain was translated into Norwegian in accordance with international
guidelines (PNKAS-N). The PNKAS-N consists of 40 items which address general pain management,
pain assessment and the use of pharmacological and non-pharmacological treatment. The study
included 238 nurses and nurse specialists at eight paediatric units and one university college.
Results: The final sample consists of 183 participants giving a response rate of 76.9%. A total of
71.2% of the questions were correct answered. The nurse specialists scored significantly higher than
the nurses (p< 0.001).
Conclusion: The nurses and nurse specialists have a high level of theoretical knowledge in several
key areas. However, the study reveals a gap between their knowledge and how the nurses and nurse
specialists actually manage pain, measured by two clinical cases. A change of attitudes seems
necessary to make them trust the patients' own assessment of pain and to administer adequate
amounts of analgesics.
627
WHEN THE WIND GOES OUT OF THE SAIL - DECLINING RECOVERY EXPECTATIONS IN THE
FIRST WEEKS OF BACK PAIN
1
2
1
2
2
J. Carstens , W.S. Shaw , K. Boersma , S.E. Reme , G. Pransky , S.J. Linton
1
1
2
CHAMP/JPS, Örebro University, Örebro, Sweden, Liberty Mutual Research Institute for Safety,
Hopkinton, MA, USA
Background and aims: Expectations for recovery are a known predictor for returning to work. Most
studies seem to conclude that the higher the expectancy the better the outcome. However, the
development of expectations over time is rarely researched and experimental studies show that
realistic expectations rather than high expectancies are the most adaptive. This study aims to explore
patterns of stability and change in expectations for recovery during the first weeks of a back-pain
episode and how these patterns relate to other psychological variables and outcome.
Methods: The study included 496 volunteer patients seeking treatment for work-related, acute back
pain. The participants were measured with self-report scales of depression, fear of pain, life impact of
pain, catastrophizing and expectations for recovery at two time points. A follow up focusing on
recovery and return to work was conducted three months later. A cluster analysis was conducted,
categorizing the data on the trajectories of recovery expectations.
Results: Cluster analysis revealed four clusters regarding the development of expectations for
recovery during a two week period after pain onset. Three out of four clusters showed stability in their
expectations as well as corresponding levels of proximal psychological factors. The fourth cluster
showed increases in distress and a decrease in expectations for recovery. This cluster also has poor
odds ratios for returning to work and recovery.
Conclusion: Decreases in expectancies for recovery seem as important as baseline values in terms
of outcome, suggesting that unrealistic expectations are detrimental for recovery.
628
EXPECTATONS MODULATE LONG-TERM HABITUATION AND SHORT-TERM SENSITISATION
TO HEAT PAIN
I. Ellerbrock, M. Arndt, A. May
Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg,
Germany
Habituation and sensitisation are two major responses to repetitively administered pain and can be
modulated by negative and positive expectations. However, not much is known about the duration
and intensity of the effects. Prior studies have shown that subjects habituate between-session over a
period of eight days and sensitize within-session. A standardized longitudinal heat paradigm of 60
suprathreshold painful stimuli was applied on 21 consecutive days in order to examine how long
expectancy modulations have effect. 60 healthy volunteers were randomly assigned to three different
groups: One group received the information that pain perception will increase (nocebo, n=20), one
group was informed that pain perception would decrease (placebo, n=20), and one group was not
given any further information (control, n=20). All participants rated pain intensity of stimuli on a visual
analog scale. In agreement with previous studies, the control group and placebo group habituated
over time. As of day 16, a plateau was reached and volunteers did not habituate any further. In the
nocebo group, this effect was not as pronounced. We found that pain ratings in the nocebo group
differed significantly from the two other groups. Congruent with previous studies, pain thresholds
increased. Our findings further highlight the importance of context information in experimental pain
studies and for the first time show the development of the habituation effect over an extended time
course. Behavioral differences between groups correlated in specific findings in fMRI on days 1, 8, 14,
and 21. These findings will be discussed.
629
IDENTIFICATION OF A GROUP OF PATIENTS IN REHABILITATION SENSITIVE TO CHANGE
ACCORDING TO THEIR BELIEFS RELATED TO PAIN
1
2
3
2
C. Favre , P. Ballabeni , F. Luthi , O. Dériaz
1
2
3
Service de Psychosomatique, Service de Recherche et Qualité, Service de l'Appareil Locomoteur,
Clinique Romande de Réadaptation SuvaCare, Sion, Switzerland
Introduction: Emotional distresses and pain related fears (PRF) i.e. fears of gravity, of pain and of
movement are recognized to influence the evolution of pain as well as the healing process. Therapies
are known to be efficient but some patients may better respond to treatments than others. The aim of
this study is to identify groups of patients sensitive to changes through time.
Methods: 616 patients with musculoskeletal injuries (mean age 43 years), hospitalized for
rehabilitation, answered 4 questions at entry, discharge and one year after. PRF variables were
determined by 7-points Likert scales. Changes were measured during hospitalization and at one year.
A cluster analysis divided patients at entry into groups with similar PRF. For each PRF variable, an
ordinal logistic regression assessed whether clusters groups may predict hospitalization and 1-year
changes. The model was controlled for confounders: age, gender, education and mother tongue.
Results: Two clusters, high and low, were identified. The high cluster predicts:
1. decrease in symptoms during hospitalization for fear of gravity (Odds ratio, 95% confidence
interval) 0.3 (0.2;0.5), fear of pain 0.3 (0.2;0.5), fear of movement 0.3 (0.1;0.4) but not for distress
1.1(0.6;0.9),
2. tendency to increase symptoms after discharge for fear of pain 1.7 (0.9;3.4) and fear of movement
1.8 (0.9;3.4).
Discussion: Patients in the high cluster generally ameliorate their symptoms during hospitalization
but tend to worsen after discharge especially for the fear of pain and movement. This underscores the
necessity to pursue ambulatory therapies after discharge with these patients.
630
MANIPULATING EXPECTATIONS OF PAIN ELICITS DIFFERENTIAL EFFECTS ON CORTICAL
AND SPINAL LEVEL NOCICEPTIVE PROCESSING
1
1
1
P. McNair , G. Lewis , A. Leys , D. Rice
1
2
2
Health and Rehabilitation Research Institute, Auckland University of Technology, Department of
Anaesthesiology and Perioperative Medicine, Waitemata District Health Board, Auckland, New
Zealand
Background and aims: People with chronic pain commonly show impaired conditioned pain
modulation. The efficacy of conditioned pain modulation is influenced by a person's expectations
regarding pain, but it is unknown if conditioned pain modulation can be enhanced through changing a
person's expectation of pain. Hence the aim was to determine if manipulation of the expectation of
pain inhibition could enhance the efficacy of conditioned pain modulation.
Methods: In 14 healthy males, the lower limb nociceptive flexion reflex was elicited in isolation (test
stimulus) and during application of two forms of conditioning stimuli. Following application of the first
conditioning stimulus (CS1), the participants were informed that the subsequent conditioning stimulus
(CS2) would elicit greater inhibition of test pain compared to the first. Lower limb flexion reflex area,
perceived pain ratings of the test stimulus, and ratings of expected pain modulation were analysed.
Results: The inhibition of perceived pain was significantly greater with CS2 compared to CS1
(P=0.01); however, there was no significant difference in the nociceptive flexion reflex area (P=0.9) or
the participant's expectation of pain modulation (P=0.8) between the two conditioning stimuli.
Conclusions: As perceived pain inhibition was enhanced but flexion reflex area unchanged following
the intervention, the intervention may give rise to an inhibition of ascending nociceptive information at
a supraspinal level resulting in reduced pain perception without influencing spinal level processing of
nociceptive input. That conditioned pain modulation can be enhanced with psychological manipulation
has relevance to clinical populations who commonly show impaired endogenous pain inhibition.
631
THE ROLE OF EXPECTATION FOR THE INTERRUPTIVE FUNCTION OF PAIN
C. Sinke, K. Schmidt, K. Forkmann, U. Bingel
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Background and aim: Pain inherently attracts attention and can disrupt other ongoing cognitive
functions. As evident in placebo research, expectation can substantially influence the perception of
pain. Here we use a simple visual attention task in combination with experimental pain stimulation to
investigate, whether expectation also modulates the “interruptive function” of pain.
Methods: 32 volunteers (14 male, age 25.21±4.14) participated in the study. Participants performed a
rapid-serial-visual-processing task either with or without painful stimulation (20s, VAS 70, presented
randomly). The task involved the detection of the letter “A” within a stream of letters and a memory
component (count occurrence of 'A'). Subjects performed 150 trials a 2s.
Participants were randomly assigned to 2 groups. One was informed that pain would boost their
performance (positive group) while the other was informed that pain impairs their performance
(negative group).
Results: The positive group expected pain to be beneficial (+1.09±1.57), while the negative group
expected an impairment (-2.36±1.39) of task performance. Performance in the memory task was
significantly better in the positive group, compared to the negative group (positive:81.35±8.25,
negative: 71,24±13.53). Intriguingly, this affected both the pain and the no-pain condition.
Conclusion: Our study shows that expectation about pain does not only affect the perception of pain
but also modulates its disruptive effect on a memory task. It is therefore important to assess the
subject's expectation about pain when investigating the disruptive function of pain experimentally.
This finding may also guide therapeutic strategies that counteract the functional impairment of chronic
pain patients.
632
THE FEAR AVOIDANCE MODEL; DOES PUNISHING RESPONSES OF SIGNIFICANT OTHER
AND SELF-EFFICACY IN ACTIVITIES HAVE ROLE IN THE MODEL
A. Soderlund, A.-C. Johansson, M. Sandborgh
School of Health, Care and Social Welfare, Malardalen University, Vasteras, Sweden
Background and aims: Fear avoidance model is well accepted as is the Social Cognitive Theory,
SCT. Studies where SCT constructs has been integrated with Fear avoidance model are rare. Thus,
the aim of this study was to explore the Fear avoidance model with the starting point from SCT.
Specifically, if punishing responses from significant others and self-efficacy in activities could have a
role within the Fear avoidance model.
Methods: A cross sectional design was used.
Subjects: Data from patients with acute whiplash associated disorders, WAD, was used to exemplify
the proposed model development. 64 patients completed the questionnaires.
Measures: Numerical Rating Scale was used to measure pain intensity (PI). The other measures
were: Pain Disability Index (PDI), Punishing Responses subscale (PR) from Multidimensional Pain
Inventory, Catastrophizing subscale (CAT) from Coping Strategies Questionnaire, Tampa Scale of
Kinesiophobia (TSK), Self-efficacy Scale in activities (SES).
Simple linear regression analyses were used. Also, Bootstraping was used to increase the reliability of
the results.
Results: Statistical prediction models showed that high pain intensity indicated high Punishing
Responses, which indicated high Catastrophizing. High Catastrophizing indicated high Fear of
movement, which indicated low Self-efficacy. Low Self-efficacy indicated high Disability, which
indicated high pain intensity. Bootstraping analyses confirmed these significant linear regression
models.
Conclusion: Results suggest a possible mediating role of PR from significant others between pain
intensity and CAT. Also, that SES can have a role between TSK and PDI. Thus, combining Social
Cognitive Theory and Fear avoidance model could increase our understanding of the pain complexity.
633
EXPECTANCY-RELATED MODULATION OF PAIN: ALTERED SENSORY PROCESSING OR
BIASED PERCEPTUAL DECISION-MAKING?
1,2,3
K. Wiech
1
4,5
6
5
6,7
1,2
, J. Vanderkerckhove , J. Zaman , F. Tuerlinckx , J. Vlaeyen , I. Tracey
2
Nuffield Department of Clinical Neurosciences, Nuffield Division Anaesthetics, Oxford Centre for
3
Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, Centre for Pain
4
Research, University of Bath, Bath, UK, Department of Cognitive Sciences, Social & Behavioral
5
Sciences, University of California, Irvine, CA, USA, Faculty of Psychology and Educational Sciences,
6
Research Group of Quantitative Psychology and Individual Differences, Faculty of Psychology and
Educational Sciences, Research Group Health Psychology, University of Leuven, Leuven, Belgium,
7
Department Clinical Psychological Science, Maastricht University, Maastricht, The Netherlands
Background and aims: Expectations have been shown to modulate pain in various contexts. This
influence is commonly assumed to be rooted in altered sensory processing. Contemporary models of
perception, however, suggest that expectations can also modulate perception by biasing perceptual
decision-making. Computational models can distinguish between changes in sensory processing and
altered decision-making as they differ in their pattern of response times for incorrect choices in a
perceptual decision-making task.
Methods: In a probabilistic cueing paradigm, healthy participants were presented with one of two
visual cues in each trial. Cue 1 signaled the application of a high intensity noxious stimulus with a
probability of 80% and of a low intensity stimulus with a probability of 20%. Cue 2 signaled a prior
probability of 50% for both intensities. Upon stimulus delivery, participants had to indicate as quickly
as possible whether they had received a low or high intensity stimulation. Using a hierarchical
diffusion model, response times and accuracies were jointly modeled.
Results: Across the sample, the expectation of high pain was related to altered perceptual decisionmaking, not to changes in sensory processing. On the individual level, however, altered sensory
processing was more likely for those with a tendency for depression. In contrast, changes in
perceptual decision-making were more pronounced in individuals scoring high on anxiety.
Conclusions: Our results challenge the current view that changes in sensory processing are a
necessary prerequisite for changes in the perception of pain and emphasize the need to understand
inter-individual differences in pain modulation.
634
DOES THE GOAL TO CONTROL PAIN PRIORITIZE ATTENTION TO A PAIN-RELEVANT
LOCATION? A SYNCHRONY JUDGMENT STUDY
W. Durnez, S. Van Damme
Department of Experimental-Clinical and Health Psychology, Ghent University, Ghent, Belgium
Recently, a new theoretical framework on hypervigilance for pain assigned a critical role to
motivational factors. Specifically, hypervigilance is suggested to be primarily driven by the goal to
control pain. Furthermore, it is construed as a mechanism activated particularly in situations in which
this goal is prioritized. Finally, it is proposed that this pain control goal drives hypervigilance by the
activation of features pertinent to the pain stimulus, in the attentional set.
We aim to investigate whether a strong pain control goal can prioritize attention to a location where
pain is expected. To this purpose, we used a synchrony judgment (SJ3). This paradigm lends us the
capability of detecting a possible location bias in attentional processing. By adding auditory cues prior
to each task trial, we established both a threat and a neutral condition. The threatening cue signaled
the possibility of receiving a painful stimulus on a fixed location, whereas the neutral cue indicated the
absence of pain. Additionally, half of the participants were assigned to a pain control condition. These
participants were told that a quick button press, following each threatening cue, would significantly
reduce the chance of receiving a painful stimulus. In the neutral group the goal to avoid pain was not
promoted.
Statistical analyses uncovered no significant attentional bias to the threatened location, neither when
threat was presented, nor when the pain control goal was activated. Both limitations of the current
study and implications for future research are discussed.
635
BEHAVIOURAL EFFECTS OF PAIN-CONTINGENT INTERRUPTIONS: AN EXPERIMENTAL
APPROACH
1
1,2
3
R. Gatzounis , M.G.S. Schrooten , G. Crombez , J.W.S. Vlaeyen
1
1,4
2
Research Group Health Psychology, University of Leuven, Leuven, Belgium, Centre for Health and
3
Medical Psychology, Örebro University, Örebro, Sweden, Department of Experimental-Clinical and
4
Health Psychology, Ghent University, Ghent, Belgium, Department of Clinical Psychological Science,
Maastricht University, Maastricht, The Netherlands
Background: A natural reaction to pain, in both acute and chronic conditions, is the suspension of
ongoing activities with the intention to resume them later. Activity interruptions are generally
considered negative. Despite their commonness in the context of pain, however, their exact
behavioural effects remain understudied. Our theoretical model predicts that interruption
consequences are not uniform, but depend on interruption characteristics, such as interruption cue
type. We investigated whether pain-contingent interruptions are more disturbing than interruptions
contingent on non-aversive external cues.
Methods: Sixty-three healthy volunteers performed a goal-directed modified Voluntary Joystick
Movement (m-VJM) task, during which they moved a joystick towards coloured rectangles. The mVJM was interrupted ten times by a secondary open-ended visuospatial task, the duration of which
was determined by the participant. For half the sample, interruptions were contingent on a painful
electrocutaneous stimulus, whereas for the other half on a non-painful non-aversive (auditory) cue.
We measured the interruption duration, total task duration (m-VJM plus interruption), and self-reported
motivation to perform both tasks.
Results: Interruption duration, total task duration, and self-reported motivation did not differ between
groups. However, the audio group participants tended to take interruptions of gradually shorter
duration, whereas the pain group oscillated more - i.e., took interruptions of varying duration.
Conclusions: The present study introduces a novel paradigm for the experimental investigation of
pain-contingent interruptions and offers indications regarding their influence on actual task behaviour.
Acknowledgements: This study was supported by the Research Foundation - Flanders, Belgium
(FWO Vlaanderen).
636
IS PAIN INTENSITY REALLY THAT IMPORTANT TO ASSESS IN CHRONIC PAIN PATIENTS?
1
1,2
3
3
3
M. Bromley Milton , B. Börsbo , G. Rovner , Å. Lundgren-Nilsson , K. Stibrandt-Sunnerhagen , B.
1,4
Gerdle
1
Rehabilitation Medicine, Dept. of Medicine and Health Sciences (IMH), Faculty of Health Sciences,
2
University of Linköping, Linköping, Clinical Dept. of Rehabilitation Medicine, County Hospital Ryhov,
3
Jönköping, Rehabilitation Medicine, Institute of Neurosciences and Physiology, Sahlgrenska
4
Academy, University of Gothenburg, Gothenburg, Pain and Rehabilitation Centre, UHL, County
Council, Linköping, Sweden
Background and aims: Patients describe the variety of consequences of their chronic pain
conditions as significant pain intensity, depression, and anxiety. We hypothesised that intensities of
common symptoms in chronic pain conditions carry important information that can be used to identify
clinically relevant subgroups. This study has three aims:
1) to determine the importance of different symptoms with respect to participation and ill-health;
2) to identify subgroups based on data concerning important symptoms; and 3) to determine the
secondary consequences for the identified subgroups with respect to participation and health factors.
Methods: This study is based on a cohort of patients referred to a multidisciplinary pain centre at a
university hospital (n=4645, participation rate 88%) in Sweden. The patients answered a number of
questionnaires concerning symptoms, participation, and health aspects as a part of the Swedish
Quality Registry for Pain Rehabilitation (SQRP).
Results: Common symptoms (such as pain intensity, depression, and anxiety) in patients with chronic
pain showed great variability across subjects and 60% of the cohort had normal values with respect to
depressive and anxiety symptoms. Pain intensity, more than psychological symptoms, showed
stronger relationships with participation and health. It was possible to identify subgroups based on
pain intensity, depression, and anxiety. With respect to participation and health, high depressive
symptomatology had greater negative consequences than high anxiety.
Conclusions: Common symptoms (such as pain intensity and depressive and anxiety symptoms) in
chronic pain conditions carry important information that can be used to identify clinically relevant
subgroups.
637
LISTENING TO THE PATIENT SPEECH AS A WORKING TOOL IN AN ONCOLOGICAL
INSTITUTION
1,2,3
1
1,3
1
1
1
J.M. Castro-Arantes , G. Harber , A.C. Lo Bianco , L. Azevedo , F.S. Ferreira , T.B. Silva , I.C.
1
Machado , Body and Finitude Research Group
1
2
3
Pain Clinic, Educational Coordination (CEDC), Brazilian National Cancer Institute (INCA), Post
Graduate Program in Psychoanalytic Theory, Federal University of Rio de Janeiro, Rio de Janeiro,
Brazil
Aim of investigation: One's own body conception when affected by an illness deeply modifies the
subjectivity, bringing about serious psychic malfunctions, that not only causes suffering but impairs
the oncological treatment. The work argues that the fundamental resource to facing problems
presented by the patient is listening to what he says, since the body and the psychic dimension are
made possible by their relation to what is said. The definition of pain by IASP, “an unpleasant sensory
and emotional experience associated with actual or potential tissue damage, or described in terms of
such damage", refers to the spoken expression of the patient.
Methods: Problems raised by care of patients at the Pain Clinic of a Brazilian Cancer National
Institute were approached. Listening to what the patient had to say about himself by the
multiprofessional team was used as the main tool to access difficulties to the treatment brought by
intense suffering. Pain intensity was measured using Numerical Pain Scale (NPS).
Results: According to the NPS, the interdisciplinary approach with patients whose speech was
considered, had important effects to control the pain state. Another important point that was observed
concerns the implications brought to the professional own subjectivity.
Conclusion: Listening to the patient was considered an important tool that implies the desire of the
professional, therefore his subjectivity. This tool can be regarded as an important means to giving
patients the proper conditions to working through the suffering brought by illness and its
consequences.
638
THE PRESENCE OF AND SEARCH FOR MEANING IN LIFE UNIQUELY PREDICT CHRONIC
PAIN-RELATED ADJUSTMENT
W. Scott, E. Bernier, M.J. Sullivan
McGill University, Montreal, QC, Canada
Meaning in life describes an individual's overall sense of direction or purpose in life. Evidence in
psychology suggests that the presence of meaning in life is an important correlate of well-being,
whereas the search for meaning may contribute to distress. The suffering and loss that may become
associated with chronic pain arguably represents a context within which individuals' sense of life
meaning may be challenged. However, limited research has examined the role of meaning in chronic
pain. The purpose of this study was to examine the associations between the presence of and search
for meaning in life and chronic pain-related outcomes. One hundred and seventy-three individuals
with chronic pain completed the Meaning in Life Questionnaire (MLQ) and self-report measures of
pain, depressive symptoms, and disability. Consistent with previous research, results indicated a two
factor structure of the MLQ, reflecting the presence of and search for meaning. Zero-order analyses
indicated that greater presence of meaning in life was associated with reduced levels of depressive
symptoms and pain-related disability. Greater search for meaning in life was significantly associated
with greater pain intensity, depressive symptoms, and disability. A hierarchical multiple regression
analysis suggested that both the presence of and search for meaning contributed significant unique
variance to the prediction depressive symptoms, controlling for pain intensity. Only the presence of
meaning contributed significant unique variance to the prediction of disability. These results suggest
that the presence of and search for meaning in life may be important correlates of adjustment among
patients with chronic pain.
639
STRUGGLING FOR SENSE OF CONTROL- EVERYDAY LIFE WITH CHRONIC PAIN FOR
WOMEN OF THE IRAQI DIASPORA IN SWEDEN
1
2
1
V. Zander , M. Müllersdorf , K. Christensson , H. Eriksson
1
2,3
2
Women's and Children's Health, Karolinska Institutet, Stockholm, School of Health, Care and Social
3
Welfare, Mälardalen University, Västerås/Eskilstuna, The Red Cross University College, Stockholm,
Sweden
As dispersed ethnic populations in the Swedish society expand, the health-care system need to adapt
rehabilitation services according to their needs. The experiences of trauma and forced resettlement
have a continuing impact on health and musculoskeletal pain, as well as the intersecting structures
that prerequisite the possibilities in the new country. To understand the specific needs of women from
the Iraqi diaspora in Sweden there is a need to illuminate the effects of pain on their everyday life.
Aims: To illuminate everyday life with chronic pain from the perspective of women from the Iraqi
diaspora in Sweden.
Methods: Qualitative interview study according to Glaser's Grounded Theory.
Results: The results from eleven interviews suggest that pain was associated with dependency on
society as well as on family. It resulted in a struggle for sense of control, framed by faith in God,
influenced by the health care system, and with support from family. The women's testimony of lack of
continuity of care resulting in recollection of lived traumas in every visit is a vital sign of the
unconscious power relations within health care. And how representatives from health care instead of
being the ones who help the women forward become the ones who held them back.
Conclusions: The results show the importance to challenge the normative assumptions imbedded in
health care and treatment for patients with chronic pain and to include the voice of “others”.
640
PREDICTORS FOR THE TRANSITION FROM CLBP TO CWP IN PRIMARY CARE PATIENTS: A
LONGITUDINAL STUDY
1
1
1
2
3
3
1
N. Jegan , A. Viniol , A. Becker , J. Barth , K. Strauch , M. Brugger , E. Baum , C. Leonhardt
1
1
Department for General Practice and Family Medicine, Philipps-University Marburg, Marburg,
2
3
Germany, Institut für Sozial und Präventivmedizin, Universität Bern, Bern, Switzerland, Institut für
Genetische Epidemiologie, Ludwig-Maximilians-Universität München, München, Germany
Background: There is ongoing discussion whether chronic widespread pain (CWP) derives from
chronic low back pain (CLBP) or is a separate condition. Our aim is to observe the transition of CLBP
to CWP in general practice to study the impact of protective and risk factors such as resilience,
coping, and comorbidities. This large cohort study is part of the German LOGIN interdisciplinary
research foundation.
Methods: For 5 months, 58 general practitioners consecutively recruited patients consulting for
CLBP. These patients completed questionnaires containing a pain drawing and scales about social
and pain characteristics (von Korff), resilience (RS-11), coping, comorbidities (SACQ) and depression
(HADS). Based on the drawing, patients were categorized as CLBP or CWP. CLBP patients were
then followed up every three months for another year with pain drawings and treatment and life event
scales. Logistic regression analysis was performed to discover predictive factors for the development
of CWP.
Results: Among the 647 recruited patients 25% showed prevalent CWP. At baseline, both groups
differed in gender, socioeconomics, depression and comorbidities. During a one year period 21% (n =
103) of the 484 Patients with CLBP at baseline developed CWP. Results of the ongoing statistical
analysis will be presented on the congress.
Discussion: There is a high risk of transition from CLBP to CWP in general practice patients. It
seems crucial to understand predictive factors which can be addressed in preventive strategies
directed towards patients in risk of developing CWP. We will present baseline and longitudinal-data
and discuss implications for treatment.
975
EMPATHY FOR PAIN IN HUMANS: A PSYCHOPHYSICAL STUDY USING PAINFUL FACIAL
EXPRESSIONS
1,2
C. Czekala , F. Mauguière
1
1,2,3
1,2
, C. Perchet , M. Frot
1,2
2
Central Integration of Pain Unit, INSERM U-1028, Bron, Claude Bernard University Lyon 1, Lyon,
Functional Neurology and Epilepsy Department, Neurological Hospital, Bron, France
3
Painful facial expressions (PFE) are a way of communicating the experience of pain to others, a
phenomenon which can be on the basis of pain empathy. While numerous studies investigated the
processing of emotional faces, few data are available on brain activities elicited by the perception of
PFE.
The aims of this study were 1) to test a battery of facial expressions which could be neutral, emotional
(6 basic emotions) or painful (Simon et al., 2008) in their capacities to elicit empathy and 2) to find a
presentation time which allowed a subconscious perception of these pictures.
Hundred students have quoted each picture on an empathy scale and hundred others, separated in 5
different groups (n=20), have done a pain categorization task with pictures presented between a mask
during 50, 100, 150, 170 or 200msec.
Our data showed that PFE elicited more empathy than all of the others pictures. Moreover, when the
pictures were presented during 100 msec, the subjects correctly categorized pain pictures without
answering by chance nor being able to consciously identify their content.
This work was preliminary to a study on neurophysiological substrates of empathy for pain elicited by
the same pictures. Thus, brain activities will be recorded with intra-cerebral electrodes in epileptic
patients while watching the pictures. This will allow to identify and define time activation of the
neuronal structures involved in the empathy for pain process and to detect whether an implicit
empathy phenomenon occurs when PFE are only perceived on a subconscious level.
976
I FEEL AS MUCH AS YOU FEEL - IF I BELIEVE IN YOU. CORRELATION BETWEEN PERCEIVED
AND OBSERVED PAIN
1
2
3
1
1
1
C. Perchet , F. Godinho , S. Mazza , M. Frot , M. Magnin , L. Garcia-Larrea
1
Central Integration of Pain in Humans, CRNL / INSERM U1028 / CNRS UMR5292 / Univ. Lyon 1,
2
Bron, France, Department of Neurology and Division of Functional Neurosurgery, Hospital das
3
Clínicas, University of São Paulo, São Paulo, Brazil, Laboratoire d'Etude des Mécanismes Cognitifs
(EMC), Université Lumière Lyon 2, Lyon, France
The sight of scenes showing human pain has been shown to increase the subjective perception of
concomitant noxious stimuli. We investigated how videos depicting medical manoeuvres evoking
different intensities of pain can modify the subjective ratings of electric shocks delivered
concomitantly.
Thirty healthy subjects (18-21 yr) received electric stimuli at two fixed intensities: painful and
innocuous, while watching high-resolution digital videos (AWA-Video®) showing actors miming pain.
Videos depicted 3 contexts: (i) abduction of the shoulder as in the investigation of rotator cuff
tendinitis; (ii) external rotation of the hip as in the investigation of hip osteoarthritis; (iii) subject's face
expressing pain without limb manipulation. Control videos with identical manoeuvres but no pain
expression were also presented. The paradigm comprised 60 blocks, each with 3 videos of same
category (painful or control) and 4 shocks of same intensity (painful or innocuous). Subjects scored
the subjective intensity of shocks following each block by means of a VAS.
The subjective rating of painful shocks associated with videos displaying pain was significantly higher
than that associated with control videos. The magnitude of pain enhancement when seeing videos
was not correlated with the intensity of pain attributed to the subjects in the videos, as assessed by an
independent sample of 220 subjects. However, the relation became significantly correlated for videos
categorised as 'reliable' by the observers.
Seeing painful medical manoeuvres is enough to enhance our own pain sensitivity. This
“compassional” effect of empathy was specific for painful stimuli only and to “reliable” expression of
pain.
977
USING COMMUNICATION AGAINST PAIN
1,2
2
M. Bras , V. Djordjevic , L. Brajkovic
1
3,4
2
Department of Psychological Medicine, University Clinical Hospital, Centre for Palliative Medicine,
3
Medical Ethics and Communication Skills, School of Medicine, University of Zagreb, Department of
4
Psychiatry, University Hospital Centre Zagreb, Centre for Palliative Medicine, Medical Ethics and
Communication Skills, University of Zagreb, Zagreb, Croatia
Pain is the most common reason why people consult a doctor, but also the most common symptom
indicating the onset of an illness or illness itself. Is pain a signal, a symptom, an emotion or an illness?
Pain is a subjective feeling and it is not easy to measure it. There is a strong and unbreakable bond
between pain and art. Pain can really motivate us, warn us, and initiate a new way of expressing
ourselves though a painting, composition, novel or song. Pain is often the bridge connecting,
elevating, moving, collecting and unifying all the layers of human sensibility making us move, scream,
show our existence and create and change something in pain. How to describe the minor key of pain,
since we assume major keys are defined by joy and pleasure? Which tonality is pain? Which colour
and shape is pain? What is the movement of pain? These are the reasons why we have decided to
start the “Using Communication against Pain” project to point through different media to pain as an
omnipresent world phenomenon and cause of human suffering. We, as humanists, need to and want
to solve this problem. Common goal of scientists, experts and artists is to build a bridge of cooperation and joint action to reduce human greatest suffering. Only our creativity and doing good will
make us feel good. Do good - feel good. Solution to all problems lies in human relationships. Homo
homini remedium!
978
THE ART OF COMMUNICATION SKILLS IN PERSON-CENTERED PAIN MANAGEMENT
1,2
2,3
M. Bras , L. Brajkovic , V. Djordjevic
1
2
2
Department of Psychological Medicine, University Hospital Centre Zagreb, Centre for Palliative
Medicine, Medical Ethics and Communication Skills, University of Zagreb, School of Medicine,
3
Department of Psychiatry, University Hospital Centre Zagreb, Zagreb, Croatia
We are witnessing the unimagined development of medical science and the clinical profession in the
treatment of patients with chronic pain, but what is left and what will always stand is a relationship
between a health professional and a patient; a relationship that opens the door to a successful
diagnosis, treatment and healing. Therefore, together with the development of personalized medicine,
there has been a parallel development of person centred medicine, which is extremely important for
patients with chronic pain. Treatment outcome often depends on the art of communicating with patient
suffering from chronic pain, and proper communication with the patient´s family, within the healthcare
professionals is extremely important as well as to develop and implement educational programs about
communication skills in the field of pain medicine. It is especially necessary to develop educational
programs dedicated to challenging situations in communication (how to break bad news, conduct a
family meeting, communicate about risks and prognosis, shared decision making and communication
about end of life decisions) and to apply experiential learning methods with the constant use of
feedback. During the lecture we will present possible models for health professional education on the
topic of good communication in person centred pain medicine, with the presentation of the medical
interview, which was developed in our laboratory of communication skills at the University of Zagreb,
School of Medicine. We will present, with video, several examples of medical interviews in working
with patients with chronic pain.
979
HEALTH INFORMATION ON INTERNET: WHAT DO CHRONIC PAIN PATIENTS LOOK FOR?
1
1
1
2
1
3
V. Piguet , A. Jesaimani , M. Besson , C. Alberque , J. Desmeules , A.-F. Allaz , C. Cedraschi
1
1,3
2
Multidisciplinary Pain Center, Division of Clinical Pharmacology and Toxicology, Division of Liaison
3
and Emergency Psychiatry, Division of General Medical Rehabilitation, Geneva University Hospitals,
Geneva, Switzerland
Background: Little is known about how chronic pain patients (CPP) use Internet regarding their
condition and medication intake.
Methods: A survey was conducted at the Geneva Pain Centre; CPP filled a questionnaire
investigating Internet use and pain-related issues.
Results: Fifty consecutive patients were contacted; 65% were females; mean age was 53 years
(SD=1.6). The majority (62%) suffered from musculoskeletal problems and a quarter from neuropathic
pain. Nearly all CPP (97%) had a computer, and 69% used Internet ≥1x/day. All CPP searched for
health information. Other reasons were email (86%) and general information (79%). Only few reported
active participation in social media. Queries concerned: neuropathic (46%), low back (39%) and
musculoskeletal (32%) pain; for analgesics: opioids (36%), antidepressants (29%) and antiepileptics
(25%); 8/10 participants taking opioids went online to find information, while this ratio was 4/8 for
antidepressants and 2/7 for antiepileptics.
A third of the respondents reported a positive influence of online information, mainly described as
encouraging them to ask questions to their physicians (43%). Few reported changing their way to
manage pain (14%). Overall, respondents felt satisfied with their health searches (57%), but also
overwhelmed with quantity (21%). Half stressed the need for recommendations on quality evaluation
and websites. Furthermore, 57% would use a website to enquire about medication leaflets or describe
treatment adverse effects.
Conclusion: Most CPP made an extensive use of Internet for health information, but only few were
actively involved online. Many respondents used the information to refine their questions and get back
to their physician.
980
PAIN ASSESSMENT AND EMPATHIC ACCURACY IN SPOUSES OF PATIENTS WITH CHRONIC
PAIN
1,2
1,2
3
2
M. Grégoire , J. Bergeron-Boucher , R. Quirion , P.-E. Michon , P.L. Jackson
1
1,2,4
2
Psychology, Université Laval, Centre Interdisciplinaire de Recherche en Réadaptation et Intégration
3
4
Sociale, Institut de Réadaptation en Déficience Physique de Québec, Centre de Recherche de
l'Institut Universitaire en Santé Mentale de Quebec, Quebec, QC, Canada
Spouses of chronic pain patients (CPS) often share, with the patient (CPP), distress related to the
caregiver burden, which may in turn reduce their ability to support them. CPS overestimate the pain of
their partner, and this might contribute to their burden. This study aimed at testing
1) whether pain overestimation of CPS for their partner also generalizes to strangers;
2) whether the perception of support given by CPS to CPP was accurate from both perspectives.
15 CPP and their spouse, and 15 healthy couples, (N =60; age range 30-65 years) were recruited.
Spouses completed a task where they assessed, using a VAS, facial expressions of pain of their
partner and strangers (UNBC McMaster database). They also completed a task in which they
assessed the level of support they would offer to their spouse, based on facial expressions. CPP also
had to assess the level of support they perceive receiving from their spouse. Pain catastrophization,
depression and empathy questionnaires were also completed by all.
CPS overestimated the pain of both their partner and strangers, compared to healthy couples.
Differences between both perspectives of support are higher in the couples exposed to chronic pain
than in the healthy couples. Pain catastrophization and depression had mediating roles in the relation
between perceived and offered support in couples exposed to chronic pain.
The overestimation of pain by CPS and some psychological characteristics could be part of the
caregiver burden and influence the level of support CPS can offer to CPP.
981
PATIENTS FACING DEATH - PSYCHOANALYSIS AT THE PAIN CLINIC OF THE BRAZILIAN
NATIONAL CANCER INSTITUTE
1,2
1
1,3
J.M. Castro-Arantes , G. Harber , A.C. Lo Bianco , Body and Finitude Research Group
1
2
3
Pain Clinic, Educational Coordination (CEDC), Brazilian National Cancer Institute (INCA), Post
Graduate Program in Psychoanalytic Theory, Federal University of Rio de Janeiro, Rio de Janeiro,
Brazil
Aim of investigation: Based on Freudian observation of the impossibility of imagining one's own
death, the research draws on literature, since Freud also noticed that through fiction it becomes
possible for one to be reconciled with death. Nonetheless, he stresses that one is reconciled not with
one's own death but that of “the other”. A Tolstoi's passage reads “the very fact of the death of
someone so close aroused, as usual, in each one to whom he was acquainted, a happy feeling that
an other had died and not oneself. There he lies, dead; not me - thought or felt each one”. Using the
psychoanalytical conceptualization of death together with the way it is dealt by in literature find the
resources needed in order to bear life when facing finitude.
Methods: In psychoanalytical method treatment and investigation occur at the same time.
Professionals listened patients experiences in the “transference relation” in view of mentioned
conceptual framework and circumscribed ways to cope with the eminence of death.
Results: Being listened at one's afflictions opened some space to the inexorability of death to being
faced. Another important point emerged respecting not only patients but professionals conducting
treatment.
Conclusion: When the subject take in his hands the decision to face the impossibility and the
inexorability of death other ways to cope with the horror of death may be opened. The professional
who decided himself to listen will not be able to dismiss his own anxiety regarding death.
982
EXPERIENCE OF SPINAL CORD INJURY NEUROPATHIC PAIN MANAGEMENT, VOICES OF
PATIENTS AND PHYSICIANS
C. Norrbrink, M. Löfgren
Division of Rehabilitation Medicine, Department of Clinical Sciences Danderyd Hospital, Karolinska
Institutet, Stockholm, Sweden
Background and aims: In a recent study, informants with spinal cord injury (SCI) and neuropathic
pain were interviewed regarding strategies and treatments for handling long-term pain, and their
experience, needs and expectations of pain management.
The present study sought to deepen our knowledge about how to design future neuropathic pain care
for individuals with SCI. Informants were sixteen of the former 18 informants and nine physicians
working with SCI neuropathic pain rehabilitation.
Methods: Data was collected using focus group interviews with the patients, and individual interviews
with the physicians. The analyses were conducted according to content analysis.
Results: Preliminary results of interviews with patients show four categories. Structure in pain care
identified a physician centered pain care where complementary treatments are rare and where pain
rehabilitation programmes are absent. Knowledge about pain described lack of knowledge and
competence about pain and it's consequences in health care. Relations with health care staff included
lack of interest, respect and understanding. Needs and desires/wishes identified needs of regular
follow-ups of pain problems, information about neuropathic pain and how to live with it, as well as role
models/peer groups. Results from interviews with the physicians show that there are large variations
in pain rehabilitation and identified need of increased knowledge and competence.
Conclusion: Rehabilitation warrants improvements in order to meet the needs of individuals with SCI
and neuropathic pain.
We thank the Swedish Cancer & Traffic Injury Society Fund (CTRF) for generous financial support.
983
INTERPERSONAL COMMUNICATION IN A PATIENT GROUP - A CASE STUDY
K.K. Roessler
Health Science, University of Southern Denmark, Odense, Denmark
Background and aim: The objective of the present study was to examine the psychological impact of
a group-oriented approach to disease management in women with polycystic ovary syndrome
(PCOS).
Method: Our case study over a 24-month period was based on a 24 weeks-cross-over study testing
the effect of group counselling in combination with a high-intensity training program on weight, pain,
and quality of life of PCOS patients. A psychodynamic approach focusing on interpersonal
communication, feed back and empathy was used throughout the period to analyse the changes in
health behavior.
Results: The participants obtained a decrease in weight (1.8 kg) and waist girth (5.4 cm) and an
increase in maximum oxigen uptake (9.9%). A decrease in pain from 2.1 to 1.5 (on a scale from 0-4)
was measured. The most salient psychological findings showed supportive relationships expressed as
group cohesion, exchange of narratives of illness and of disorder-specific aspects. As narratives
shame over hirsutism and lack of food control and weight related pain are named. Individual
relationships between the participants were important for changes in behaviour, especially those
generating feedback from the other participants and thereby, reducing social isolation. The results
were most encouraging in the group that had initial counselling sessions before the physical
intervention.
Conclusion: It can be concluded that group counselling sessions focusing on supportive
relationships followed by high-intensity aerobic training have beneficial effects on wellbeing, health
and exercise behaviour.
984
DEFENSE MECHANISMS USED BY NURSES AND THEIR ATTITUDES TOWARDS PATIENTS
WITH PAIN
M. Yildirim, M. Sabit, M.S. Ilday, E. Ates, S. Dursun
School of Nursing, Haliç University, Istanbul, Turkey
Background and aim: Nursing is a profession with many stressful conditions; and as a reaction to
stress, the nurses may use certain defense mechanisms subconsciously in order to protect their
mental health. Due to subjectivity of pain, giving nursing care to a patient with pain is more
challenging. Thus; the study is aimed to investigate the relation between the defense mechanisms
that the nurses use and their attitudes towards patients with pain.
Method: This descriptive study was conducted in four public and two private hospitals with written
permissions. The sample included 331 nurses who accepted to participate to the study. The data
were collected by data collection form which is created by the researchers and Defense Style
Questionnaire (DSQ). DSQ measures mature, neurotic and immature defense styles. The data were
evaluated with descriptive statistics, student-t test, One Way ANOVA and Pearson Correlation
Analysis.
Results: 77.6% of the nurses were female and 51.1% were college graduated. 29% of the nurses
stated that sometimes they try placebo after the patient express pain. The nurses who are graduated
from a medical vocational school were using immature defense mechanisms significantly more than
the nurses graduated from a nursing college. The nurses who never believe the patient's pain were
using mature defense mechanisms significantly less than the nurses who believe the patient's pain.
Conclusions: Defense mechanisms used by nurses may be slightly related with their attitudes to the
pain patient. The other possible reasons of overestimation/underestimation of pain by nurses should
be investigated.
985
ASSOCIATIONS BETWEEN APPROACH TO ACTIVITY ENGAGEMENT AND OPIOID USE IN
CHRONIC PAIN
N.E. Andrews
1
1,2,3
3
1
, J. Fleming , J. Strong , P.J. Meredith
1
2
Division of Occupational Therapy, University of Queensland, Occupational Therapy Department,
The Professor Tess Cramond Multidisciplinary Pain Centre, The Royal Brisbane and Women's
Hospital, Brisbane, QLD, Australia
3
Background and aims: The way in which an individual with chronic pain habitually approaches
activity engagement is thought to impact on daily functioning with both avoidance of one's daily
activities and overactivity (activity engagement that significantly exacerbates pain) postulated to lead
to functional decline. Various cross sectional studies have linked self reported avoidance and
overactivity to gross measures of disability. However, there is a need to more closely examine the
impact that approach to activity has on an individual's daily life. This study aimed to examine the
effect of approach to activity engagement on daily opioid use.
Methods: Sixty two participants with chronic pain participated in the study. Participation involved
completing a demographic form; filling in self-report measures of overactivity and avoidance (the Pain
and Activity Relations Questionnaire); and providing a record of prescribed pain medications.
Participants then completed five days of data collection where they recorded their pain medication
intake in a diary.
Results: Individuals reporting higher levels of overactivity were more likely to be prescribed opioids
and more likely to take PRN opioid medication over the five days of data collection. Higher levels of
overactivity were associated with more frequent PRN opioid use over the five days but not with the
oral morphine equivalent daily dose or the discrepancy between the prescribed and actual daily
doses. Avoidance and the interaction between avoidance and overactivity were not significantly
associated with any of the outcome variables.
Conclusions: The results suggest that overactivity is related to more frequent opioid use.
986
BEHAVIOURAL MEDICINE INTERVENTION VIA INTERNET OR FACE TO FACE IN ACUTE
WHIPLASH ASSOCIATED DISORDERS - A RANDOMIZED CONTROLLED TRIAL
1
1
A. Bring , P. Åsenlöf , A. Söderlund
1
2
2
Department of Neuroscience, Uppsala University, Uppsala, School of Health, Care and Social
Welfare, Mälardalen University, Västerås, Sweden
Background and aims: Despite increasing knowledge of the impact of psychosocial factors on the
development of chronic disabling symptoms in Whiplash Associated Disorders (WAD), there is still a
lack of early management approaches aiming to influence these factors. The present study aimed at
investigate the effects of an individually tailored behavioural medicine intervention delivered via;
Internet (IT) or face-to-face (FtF), compared to standard self-care instructions (SC), in pain related
disability (PDI), pain intensity, self-efficacy in daily activities (SES), catastrophising (CAT) and fear of
movement/(re)injury (TSK).
Methods: A randomized, prospective, three-group design. Fifty-five participants with acute WAD,
recruited from two emergency clinics in Sweden, were randomly allocated to either tailored
behavioural medicine intervention delivered via IT or FtF or to SC, within 2-4 weeks from the accident.
Follow-ups at 3-, 6- and 12-months.
Results: Both IT and FtF showed a larger decrease in pain related disability than SC. Significant
differences between the groups in overall treatment effect were shown in PDI (p=.009), SES (p=.03),
TSK (p=< .001) and CAT (p=.002). All treatment groups improved significantly over time in all in all
outcomes, except for TSK and CAT in SC group.
Conclusions: It is possible to influence disability and potential prognostic biopsychosocial factors in
acute WAD, and to sustain the effects up to 12 months after treatment. Also, it seems possible to
reach treatment effects in both face-to-face sessions and with techniques online including e-mail
support. The results are relevant for future development of early secondary preventive management
in acute WAD.
987
VALUED NON-PAIN GOALS ATTENUATE AVOIDANCE BEHAVIOR IN THE CONTEXT OF PAIN
1,2
1
1
2
1,3
N. Claes , K. Karos , A. Meulders , G. Crombez , J.W.S. Vlaeyen
1
2
Research Group on Health Psychology, KULeuven, Leuven, Department of Experimental-Clinical
3
and Health Psychology, Ghent University, Ghent, Belgium, Faculty of Psychology, Department of
Clinical Psychological Science, Maastricht University, Maastricht, The Netherlands
Background and aim: Fear-Avoidance models propose that dysfunctional beliefs about pain induce
a pattern of defensive responses, possibly leading to the development, maintenance, and
exacerbation of chronic pain disability. However, pain-related fear does not occur in a motivational
vacuum, but in a context of multiple, often competing goals. Therefore, Fear-Avoidance models might
benefit from including a motivational perspective.
Methods: We used an adapted Voluntary Joystick Movement paradigm. In a within-subjects design
(N=55) participants manipulated a joystick to the left/right in the experimental (competing goals)
condition, and upward/downward in the control condition or vice versa. In the experimental condition,
one movement (CS+) was followed by both a painful unconditioned stimulus (pain-US) and a
monetary reward (reward-US), the other movement (CS-) was not. In the control condition, the CS+
movement was only followed by the pain-US, the CS- movement was not. During free choice trials
after each block, participants performed either the CS+ or the CS- movement.
Results: Participants chose to perform the CS+ movement more often in the experimental condition
than in the control condition. Also, participants were slower initiating CS+ than CS- movements in the
control condition, whereas in the experimental condition this difference in response latencies
vanished.
Conclusion: This study presents preliminary experimental support for the influence of motivational
factors on pain avoidance. When confronted with pain, inclusion of a valued non-pain goal attenuates
avoidance behavior, as indicated by differential response latencies and choice behavior.
Acknowledgements: This study was supported by Research Foundation - Flanders, Belgium (FWO
Vlaanderen).
988
THE DEFENSIVE BEHAVIOR INDUCED BY FEAR CAN INHIBIT THE NOCICEPTION PRODUCED
BY NEUROPATHIC PAIN MODEL IN MICE?
1
1
L.M. dos Reis , C. Kosour , A.L.M. Canto-de-Souza
1
2
2
Nursing Department- Physiotherapy Course, Federal University of Alfenas (UNIFAL), Alfenas, Dept
Psychology-Psycobiology, Federal University of São Carlos - UFSCar, São Carlos, Brazil
Background and aims: The sciatic nerve constriction (SNC) is largely used for neurophatic pain in
rodents model. The present study investigated if nociceptive response induced with SNC can be
modulated by defensive behavior in mice.
Methods: Male Swiss mice (n=10-15/group) without (SHAM) or with SNC were exposed to a cage
containing a live Long Evans rat (R) or a toy rat (TR). The exposure cage was divided into three
compartments [the home cage (protected compartment), the surface (unprotected compartment) and
the predator compartment]. Mice had free access between the home cage and surface area via a
door (5 x 8 cm). The surface and the rat compartment were separated by a wire mesh screen. The
following measures were recorded: nociceptive response [time (in seconds) spent on scratching the
leg with SNC] and defensive behavior [total entries in surface (TE), percentage of entries and
percentage of time spent in the protected area (% PE and % PT).
Results: The animals with SNC spent more time scratching the leg than SHAM group
[(F(1,61)=26.97, p< 0.05)], and this nociceptive response was decreased in mice exposed to the live
rat [(F(1,61)=21.11, p< 0.05)]. Both SHAM and SNC mice displayed increased % PE [(F(1,61)=12.95,
p< 0.05] and % PT [F(1.61)=20.91, p< 0.05] when compared with TR.
Conclusions: The exposure of mice to the predator (rat) elicits defensive response in both SHAM
and SNC mice as well as attenuates nociceptive response induced by SNC.
989
BODY IMAGE AND PHYSICAL ACTIVITY IN NONSPECIFIC LOW BACK PAIN: SUBGROUP
DIFFERENCES DUE TO THE AVOIDANCE-ENDURANCE-MODEL OF PAIN
1
2
3
3
2
1
C.G. Levenig , M. Kellmann , J. Kleinert , I. Boldt , T. Mierswa , S. Sudhaus , M.I. Hasenbring
1
1
2
Medical Psychology and Medical Sociology, Faculty of Sport Psychology, Ruhr-University Bochum,
3
Bochum, Health and Social Psychology, Institute of Psychology, German Sport University, Cologne,
Germany
Background and aims: There is growing evidence that fear-avoidance- and endurance-related pain
responses have an impact on the maintenance of low back pain (LBP). However, little is known about
the mediating mechanisms. Individual body image and physical activity in daily life may play an
important role, although research is rare. The main purpose of this study was to investigate individual
body image and the level of self-reported physical activity among subgroups of non-specific LBPpatients showing maladaptive compared to adaptive pain responses due to the AvoidanceEndurance-Model (AEM).
Methods: 97 LBP-patients from an exercise treatment setting completed several questionnaires
(Avoidance-Endurance-Questionnaire AEQ, Beck Depression-Inventory-Primary Care BDI-PC,
Frankfurt-Body-Concept-Scales FKKS, physical activity questionnaire). Based on BDI-PC and AEQ
the sample was distinguished into four subgroups: adaptive (AR), fear-avoidance (FAR), eustress
endurance (EER) and distress endurance (DER) responses to pain. Separate ANOVAs were
computed to inspect subgroup differences, using SPSS-21.
Results: EER and AR patients showed a more positive body image in the FKKS-scale “Health”
compared to FAR (p < .01) and DER (EER: p < .001, AR: p < .01). DER revealed a more negative
“Self-acceptance of one's body” (EER: p < .01, AR: p < .05). No subgroup differences were found for
“Physical efficiency” or self-reported physical activity.
Conclusions: Fear-avoidance and distress-endurance patients revealed a more negative body image
in several aspects that may play a role in the maintenance of pain despite the same level of selfreported physical activity. Improving body image could be an important goal of exercise treatments in
these patients.
990
INDIVIDUAL DIFFERENCES IN FACIAL RESPONSES TO PAIN - THE ROLE OF INHIBITORY
FUNCTIONING
1
1
1,2
A.J. Karmann , S. Lautenbacher , M. Kunz
1
2
Physiological Psychology, University Bamberg, Bamberg, Biological Psychology, Ludwig-Maximilian
University Munich, Munich, Germany
Background and aims: Individuals vary greatly in their tendency to facially communicate their
experience of pain. Imaging data suggests that these differences in facial expressiveness are
accompanied by different activations in inhibitory circuits; with low expressive individuals actively
inhibiting their expressiveness. However, it is not known why individuals exert more or less inhibitory
control over their facial responses. The aim of the present study was to investigate whether the ability
to inhibit (inhibitory functioning) might help to explain differences in facial expressiveness.
Methods: Facial expressiveness to phasic heat pain was assessed in 49 healthy participants using
facial electromyography (EMG) and the Facial Action Coding System (FACS) (criterion variables).
Inhibitory functioning measured by the Antisaccade task, Stroop task and Impulsive Behaviour Scale
(UPPS) was used as predictor variable.
Results: We found that the performance in the Antisaccade task could significantly predict the degree
of facial expressiveness in response to pain (both EMG and FACS); with low expressive individuals
showing a higher ability to inhibit saccadic eye movements. Neither the UPPS nor the Stroop
variables were able to make this prediction.
Conclusion: Differences in facial expressiveness in response to pain are closely linked to the
individuals' ability to inhibit automatic motor responses. Given that social display rules (social norms
about the appropriateness of emotional displays) rather favor the suppression of pain, those
individuals who have a better capacity to inhibit automatic responses seem to have implemented
these display rules more successfully.
991
DETERMINATION OF DYSMENORRHEA CHARACTERISTICS OF UNIVERSITY STUDENTS AND
THEIR PRACTICES FOR COPING WITH DYSMENORRHEA
F. Üstüner Top, D. Küçük Alemdar
Giresun Universty, Giresun, Turkey
Background and aims: The purpose of this descriptive study was to determine dysmenorrhea
characteristics of students receiving education in Giresun University Faculty of Health Sciences in
Turkey and their practices for coping with dysmenorrhea.
Methods: This study was conducted in a descriptive way to determine dysmenorrhea characteristics
of students receiving education in Giresun University Faculty of Health Sciences Department of
Nursing and Midwifery in Turkey and their practices for coping with dysmenorrhea. No sample group
was selected and all of the 346 students were included in the study.
Results: As a result of the study, it was determined that average age of students was 20.56 and 58.1
% of them experienced dysmenorrhea every month. In the study, it was found out that regarding the
dysmenorrhea, 23.7% of students had a sudden onset pain, 74.9 % had a slow progress, 42.5 % had
tingling pain. 33.2 % of students had a pain that lasted for 12-24 hours and 56.9 % had a pain
progressing from stomach to waist. Regarding practices performed by students for dysmenorrhea,
73.1% indicated that it is useful to sleep, 46.8 % to get a massage, 33.2 % to have a hot application,
37 % to take a shower and 22.3 % to pray.
Conclusion: In consequence of the study, it was determined that a great majority of students had a
tingling pain that lasted for more than 12-24 hours. Practices such as sleeping, getting a massage
and taking a shower were the most frequent practices for dysmenorrhea.
992
VOCALIZATION IN PAIN: AN UNDERSTUDIED REALM IN HUMANS
S. Lautenbacher, Y. Hogenmüller, M. Kunz
University of Bamberg, Bamberg, Germany
Background and aims: Nonverbal vocalization (like moaning, sighing) has been claimed to be a
reliable accompaniment of pain in animals and humans. Nevertheless, objective and quantitative
vocalization research has yet been missing for humans. The diagnostic emphasis on verbal report has
most likely produced this neglect. However, nonverbal vocalization might hold the potential to serve
as a valid pain indicator in non-verbal individuals like patients with dementia, who are not able to
provide self-report of pain. Vowels are ingredients of moaning and sighing and thus, were investigated
in the present study whether they can signal pain.
Methods: Forty students were studied for changes in loudness and pitch when producing 5 different
vowels (instructed repetition of single vowels (A, O, U, E, I)) during pain (hot water immersion, 46.5
°C) compared to baseline. “A”, “O” and “U” are typical ingredients of moaning and sighing in German
whereas “E” and “I” are atypical in this respect.
Results: Pain stimulation significantly increased the loudness of all 5 vowels but only increased the
pitch (F0) of the 3 vowels that are more typical for moaning and sighing (A, O, U).
Conclusions: Accordingly, the pitch of certain vowels in vocalizations may indicate distress or even
more specifically pain and may provide a clinically feasible and objective behavioral measure of pain.
993
DIFFERENTIAL HYPOMIMIA REGARDING FACIAL EXPRESSIONS OF PAIN IN PARKINSON
PATIENTS
1
1
2
2
J. Priebe , M. Kunz , P. Rieckmann , C. Morcinek , S. Lautenbacher
1
1
2
Physiological Psychology, University of Bamberg, Neurological Clinic, Sozialstiftung Bamberg,
Bamberg, Germany
Background: Hypomimia which refers to a reduced degree in facial expressiveness is a common
symptom in Parkinson (PD) patients especially in the Off state (no dopaminergic medication). The aim
of our study was to investigate how hypomimia in PD-patients affects facial expressions of pain which
plays a crucial role in pain communication
Methods: The facial expressions of 15 PD-patients in the Off and the On and matched controls to
phasic heat-pain were recorded and analyzed using the facial action coding system.
Results: Qualitative analysis revealed a differential hypomimia regarding facial expressions of pain:
Occurrence of movements of the eyebrows and the upper lip was reduced in the Off-state. Thereby,
although the activities of the upper lip and the eyebrows increased in the On relative to the Off, the
level of the healthy controls was not reached. In contrast, orbicularis oculi activity (narrowed eyes)
were not affected in patients.
Conclusions: This data pattern fits a differential hypomimia hypothesis: As the facial expression of
pain can be seen as a multidimensional response system encoding both the affective
(eyebrows/upper lip) and the sensory component (narrowed eyes) , the encoding of the sensory
component seems to be preserved in PD-patients. The facial communication of the affective
component is reduced.
From an evolutionary perspective it makes sense that the facial expression of pain -a signal for harm
and a trigger for empathy and help - is mainly preserved in PD. It remains unclear, why this applies
only for the sensory component of facial pain expression.
994
ASSESSMENT OF PAINFUL FACIAL EXPRESSIONS BY NURSES AND ITS RELATION WITH
THEIR CLINICAL EXPERIENCE
1
2
3
M. Yildirim , S. Ünver , N. Kanan , N. Akyolcu
1
3
2
School of Nursing, Halic University, Istanbul, Department of Nursing, Trakya University Health
3
Science Faculty, Edirne, Istanbul University, Nursing Faculty, Istanbul, Turkey
Background and aims: The objectivity of pain makes it harder to assess; thus facial expressions of
patients with pain should be considered by caregivers. Therefore; the aim of the study is to investigate
the ability of nurses to assess the painful facial expressions of pain patients and its relation with their
clinical experience.
Methods: The nurses who were a member of a social networking website were informed about the
aim of the study and were asked to participate. The study was carried out descriptively with total 126
voluntary nurses. An online survey system was used for data collecting. The survey contained 14
questions for demographic information and nurses' clinical experiences. The nurses asked to score
the pain level of the individuals in 12 photos obtained online by searching the words “pain patient”.
For evaluation of pain; 0-10 Numeric Pain Scale was used. The data were evaluated with descriptive
statistics, Mann Whitney U and Kruskal Wallis Test.
Results: It was found that the female nurses were giving significantly higher pain scores than male
nurses (p< 0.05). As much as the nurses stated that they believe their patient's pain; the scores they
gave to the photos were increased significantly (p< 0.05). The nurses who think that the patients
exaggerate their pain behaviours; gave significantly lower scores (p< 0.05).
Conclusions: Nurses' perception of pain behaviours can be affected by gender and their beliefs.
Therefore; behavioral sciences related in-service training programs can be done to provide a better
nurse-patient communication in painful situations.
995
SEXUAL DYSFUNCTION IN WOMEN WITH ENDOMETRIOSIS AND CHRONIC PELVIC PAIN.
QUALITATIVE STUDY
A.C. Falcone, B.H. Mellado, F.J.C. dos Reis
Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto - Universidade
de São Paulo, Ribeirão Preto, Brazil
Background and aims: Endometriosis is an important cause of Chronic Pelvic Pain (CPP), and CPP
is reported to influence sexual life in men and women. However, there is no detailed description of
patients point of view based on qualitative studies. Our objective is to explore the sexual experience
of women living with endometriosis and CPP.
Methods: This is a qualitative study based on interviews through focus groups. Fifteen women were
included in three focus groups with five of these women in each. All of them had confirmed diagnosis
of endometriosis by laparoscopy, and at least six months of follow up.
Results: We observed hypoactive sexual desire in discourse like "I spent more than a month without
having sex" or “…they talked about having sexual intercourse. I no longer feel desire…”, and manifest
deterioration of conjugal life “I´m divorced, I have no boyfriend, I do not want it because I think the first
thing the person will want is having sex and I do not want it…”.
Conclusion: Regarding the pain, women begin to avoid the partner and keep up to fear sex. Almost
all women with CPP present fear of dyspareunia, and in some cases resulting in divorce or the option
of taking a life alone, without the presence of a partner.
996
COMMON SYMPTOMS, COMMON CURE? DESCRIBING DIFFERENT STAGES OF SICK LEAVE
DURATION IN NORWAY
1,2
1,2
1,2
2,3
3
H.B. Jacobsen , K.W. Hara , P.C. Borchgrevink , A. Woodhouse , M.S. Fimland , J.H.
3
2,4
Bjørngaard , T.C. Stiles
1
Department of Circulation and Medical Imaging, Norwegian University of Science of Technology,
National Competence Centre for Complex Symptom Disorders, St. Olavs University Hospital,
3
4
Department of Public Health, Department of Psychology, Norwegian University of Science of
Technology, Trondheim, Norway
2
Background and aims: Norway has a high rate of sick leave and spends 5 % of the GDP on
sickness and disability benefits, far more than neighboring countries. This study aimed to describe the
somatic, psychological, and social factors associated with different stages of sick leave.
Methods: During 2012, 181 patients on long-term sick leave were consequtively recruited from an
outpatient clinic and asked to answer an extensive survey. Several outcomes were reported,
addressing somatic, psychological and social symptoms. In cross-sectional analyses, sick leave
duration was dichotomized as > or < 1-year, based on Norwegian legislation. Linear and logistic
regressions were used to estimate population probabilities and means.
Results: Both populations had a high prevalence of chronic pain (< 74%; >77%) fatigue (< 83%;
>74%), anxiety (< 62%; >49%) and depression (< 51%; >43%). Population means and probabilites
showed that symptoms did not increase with longer duration. Pain remained stable, while fatigue,
anxiety and depression showed decreasing trends. Sleep problems increased >1-year. Relationship
with family, friends co-workers and work place, showed a worsening trend in the >1-year population.
More fear-avoidance with regards to work, less fear-avoidance with regards to physical activity, and
less catastrophizing thoughts about pain was also indicated in this population.
Conclusions: Analyses of patients on long-term sick leave indicate that social symptoms become
more adverse with duration. With the exeption of pain, somatic and psychological symptoms
decrease. This should be adressed in prospective studies, as well as treatment and rehabilitation.
997
CHILDHOOD NEGLECT IS RELATED TO SOME - BUT NOT ALL - GENERAL WIDE-SPREAD
PAIN CONDITIONS
V. Meineche-Schmidt
Private Pain Clinic, Herlev, Denmark
Background: Fibromyalgia, whip-lash and hypermobility is poorly understood. Most patients are
females. Often, the difference between complaints and findings is a challange for health and social
workers. Furthermore it has been demonstrated that no car-impact threshold can be defined for the
development of WAD - challenging the biomedical nature of the condition.
Material and methods: Case-control study comprising 500 consequtive female patients attending a
private multidiciplinary pain clinic during the period 2010-2012. Cases were 92 patient with WAD, 80
patients with fibromyalgia and 27 patients with hypermobility. Controls were 301 patients remitted in
the same period with: slipped discs or arthrosis, conservative treated or operated. A questionnaire
was mail to all patients, questions were related to childhood conditions (parental disease, abuse and
violence), school experiences and early adolence depressions. Telephone follow-up was done twice.
Overall, primary question was phrased: "Did you expirience a happy and safe childhood". Could be
answered ´Yes´ or ´No´.
Results: A total of 65% responded.
Patients were analysed in these groups according to the primary question:
1) Fibromyalgia versus controls, p=0.02
2) Hypermobility versus controls, p=0.32
3) WAD versus controls, p=0.86
Conclusion: Fibromyalgia seems to be related to life expirience and stress during childhood. This
could not be demonstrated in patients with hypermobility or patients with WAD. The finding suggests
that the treatment approach should be tailored to the type of wide-spread pain condition.
377
PEDIATRIC PAIN IN PORTUGAL: RESULTS OF SENSITIZATION AND FORMATION
1,2
3
3
4
5
L. Batalha , L. Costa , G. Reis , F. Jacinto , R. Machado , P. Santos
1
2
6
3
Nursing School of Coimbra, Health Sciences Research Unit - Nursing, Hospital and University
4
Centre of Coimbra, EPE-Pediatric Hospital of Coimbra, Coimbra, Hospital of Barlavento Algarvio,
5
6
EPE, Portimão, Hospital Center of Cova da Beira, EPE, Covilhã, Hospital Center of Trás-os-Montes
e Alto Douro, EPE, Vila Real, Portugal
Introduction: Sensitization and formation of health professionals in the area of pain was a national
strategic option since 2001, but its impact on care is unknown. The aim was to evaluate the impact of
sensitizing and formatting events conducted over the past ten years in the care provided by nurses for
hospitalized children, in the area of pain.
Method and material: An observational, descriptive, cross-sectional retrospective study of records
within 24 hours, performed by nurses in the clinical process of children until the 18 years.
Results: Of the 830 cases analyzed clinical history of pain was recorded at 47.8%, being well
prepared and performed in the first 24 hours of hospitalization. Within eight hours the record of the
pain assessment was 36.7%. The choice of the pain scale was adequate in 59.3% of cases.
Approximately 79.9% of the children showed no or mild pain was 12.5%. There was a good pain
management in 92.5% of the children. In about 42.2% of the cases were no reports of
pharmacological interventions and 15.8% of non-pharmacological interventions.
Discussion: The cares improved in the last decade, but there are still gaps in the information
collected in the history of pain, pain assessment and decision making for a judicious prescription of
interventions based on the pain assessment.
Conclusion: The investment made in the last decade in sensitizing and formatting of health
professionals proved to be a wise strategic choice in the increase of the good pain control.
378
IMPROVING THE SELECTION OF TRUE INCIDENT CASES OF LOW BACK PAIN BY
SCREENING RETROSPECTIVE ADMINISTRATIVE DATA
1
2
3
1
N. Beaudet , J. Courteau , P. Sarret , A. Vanasse , The PRIMUS Group
1
Family & Emergency Medicine, Université de Sherbrooke, Faculty of Medicine & Health Sciences,
Centre de Recherche Clinique Etienne-Le Bel, Centre Hospitalier Universitaire de Sherbrooke
3
(CHUS), Physiology & Biophysics, Université de Sherbrooke, Faculty of Medicine & Health Sciences,
Sherbrooke, QC, Canada
2
Background: Identifying the onset of low back pain (LBP) is difficult, limiting the capacity to
determine the incidence of LBP at the population level and further identify risk factors. In the literature,
incidence cohorts have been built with patients initially considered LBP-free for 6 to 12 months prior to
their selection. However, this “clearance period” might not be sufficient to exclude recurrent patients
having experienced previous LBP episodes and therefore might contaminate the number of true
incident cases.
Methods: Using the Canadian province of Quebec physicians' claims database, a cohort of prevalent
claims-based recurrent LBP patients was built for 2007. The medical history of the 81329 patients was
screened for a period of 11 years. Patients with a previous episode of LBP were excluded. Positive
predictive values (PPV) and Kappa statistics were calculated to determine the optimal clearance
period for capturing true incidence cases.
Results: A very good convergence for PPV and Kappa was found with a 7-year clearance period.
The 5-year incidence rate of adult claims-based recurrent LBP was 325 per 100 000 person-years.
Males of 18 to 34 years of age were found 1.18 times more at risk than their counterparts. Altogether,
elderlies over 80 years had 52% more new cases than the 18-34 group. The annual incidence
decreased by 12% between 2003 and 2007.
Conclusion: Screening the medical history of LBP patients would provide more accurate incidence
rates. This will allow the valuation of medical and pharmacy costs for new cases of claims-based
recurrent LBP patients.
379
IDENTIKIT OF AMBULATORY PATIENTS AFFERENT TO HUB PAIN THERAPY CENTER IN
NORTHERN ITALY
1
2
3
3
3
4
R. Bednarova , L. Miceli , R. Marzi , E. Storelli , P. Sorbello , K. Kussini , U. Colonna
1
1
2
Department of Pain Medicine and Palliative Care, Hospital of Latisana, Latisana, Department of
3
Anestesia and Intensive Care Medicine, University of Udine, Udine, Department of Pain Medicine
4
and Palliative Care, Hospital of Novara, Novara, General Practitioner, Latisana, Italy
Backgrounds and aims: We conducted a survey to determine typology of patients seeking a pain
center and the degree of satisfaction with the offered service.
Methods: We analysed 105 anonymous questionnaires collected between January and April 2013
after a pain therapy visit.
Results:
Sex 28% ♂ 72% ♀
Waiting list <7days: 18%, <30days: 34%,
<120days: 29%, >120days: 10%
Medium age 62,3 years
Evaluation of Profesionality 94/100
Medium NRS at home 7,4
Seek pain therapy on request of General
Practitioner 62%, Hospital personal 23%, Others
15%
Analgesics NSAID 38%, Acetaminophen 30%,
weak opioids 25%, strong opioids 23%
Three major defects Long Waiting list 35%, Short
opening hours 28%, absence of continuous
telephone availability 8%
Constipation 49,5%
Three major positive items Courtesy and listening
22% Time dedicated to patients 25%, gentleness
22%
Number of consulted doctors before pain unit visit Quality of the service relative to aspectations
<2: 32%, between2-4: 38%, >4: 30%
Better 74%, Equal 25%, Worse 1%
Medium pain lenght 63 months
Evaluation of the courtesy 92/100
[Results]
Conclusions: Old patients uselessly seek various specialists for chronic pain that in average is
experienced for more than 5 years; their general practitioner send them finally to a pain therapy
center treating their pain meanwhile not only with NSAID but also with acetaminophen and opioids,
being a sign of good agreement with italian pain law 38/2010.
Half of the patients suffer from constipation, and hence it is in our opinion appropriate choosing
analgesics that limit this problem.
380
THE INFLUENCE OF PARTNERS ON MUSCULOSKELETAL CONSULTATIONS IN PRIMARY
CARE PATIENTS
P. Campbell, M. Shraim, K. Jordan, K. Dunn
Keele University, Stoke-on-Trent, UK
Background and aims: Research has shown illness concordance between couples for some
conditions (hypertension, allergies, depression, peptic ulcers, heart disease) but not others (e.g.
diabetes, stroke). To date little information exists on concordance between couples for
musculoskeletal conditions. The aim of this study is to determine whether a primary care consultation
for a musculoskeletal condition is more likely if a person's partner also consults for a musculoskeletal
condition.
Methods: Analysis of 13,057 couples (27,014 patients) using data from a UK Primary Care medical
record database (CiPCA). The main outcome measures were recorded morbidity codes relating to
any musculoskeletal condition, specifically regional disorders (back, knee, neck, shoulder, foot) and
osteoarthritis during the course of one year. Associations between consultations for musculoskeletal
conditions in females and their male partners were analysed using logistic regression to estimate
odds ratios (OR) with 95% confidence intervals (95% CI).
Results: 8292 patients (31%) were classified as having a musculoskeletal consultation. Women
whose partner had a musculoskeletal consultation were more likely to have consulted for a
musculoskeletal condition (adjusted OR 1.22, 95% CI 1.12 to 1.32). This association was highest for
shoulder disorders (OR 1.91, 95% CI 1.06 to 3.47).
Conclusions: There is an increase in the likelihood of a musculoskeletal consultation if a partner has
also consulted for a musculoskeletal condition. Possible explanations include the shared environment
and shared illness beliefs that couples may have. These findings raise implications on the
consideration of social factors and partner effects for musculoskeletal consultations in primary care.
381
PAIN IN HOSPITALIZED PATIENTS? A CROSS-SECTIONAL STUDY IN A COMMUNITY
HOSPITAL IN VIENNA
1,2
1
2
W. Jaksch , R. Reichhalter , G. Handl , B. Gustorff
1
1
2
Anaesthesiology, Intensive Care, Pain Medicine, Nursing School, Wilhelminenspital of Vienna,
Vienna, Austria
Background and aims: Our efforts of the last years were directed to optimize postoperative pain
management. Until now we had no information about the pain situation of patients on nonsurgical
wards.
Methods: In cooperation with our school of nursing we performed a cross sectional study. More than
50 students interviewed patients (age ≥ 18a) on all wards of the hospital using a standardized
questionnaire on one day.
The primary endpoint was the prevalence of pain.
th
Results: On the 11 of March 2013 455 patients (out of 1000) were included in this study.
pain prevalence
pain intensity (mean)
all patients
208/455 = 45,7%
4,55
female
126/256 = 49,22%
4,60
male
82/199 = 41,21%
4,48
nonsurgical departments
126/277 = 45,5%
4,82
surgical departments
82/178 = 46,1%
4,13
[pain prevalence and intensity (NRS 0-10)]
We could not observe age-related differences in pain prevalence.
Pain assessment and pain documentation was performed more often on surgical departments.
Patients on surgical wards rated the quality of pain management higher than patients on nonsurgical
wards.
Conclusions: We assessed an overall prevalence of pain of 45,7% in our hospital. Significantly more
females reported pain than males. No differences in pain prevalence between surgical and
nonsurgical departments were detectable. The pain intensity was significantly higher on nonsurgical
wards.
Pain therapy programs also on nonsurgical departments are warranted!
382
REDUCED COLD PRESSOR PAIN TOLERANCE AMONG SMOKERS AND PREVIOUS
SMOKERS. THE TROMSØ STUDY
1,2
3
4,5
A. Johansen , C.S. Nielsen , A. Stubhaug , H. Schirmer
1
6,7
2
Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Department
3
of Community Medicine, University of Tromsø, Tromsø, Department of Mental Health, Norwegian
4
Institute of Public Health, Department of Pain Management and Research, Oslo University Hospital,
5
6
7
University of Oslo, Oslo, Department of Clinical Medicine, University of Tromsø, Division of
Cardiothoracic and Respiratory Medicine, University Hospital of North Norway, Tromsø, Norway
Background and aim: Experimental studies indicate antinociseptive effects of cigarette smoking and
nicotine treatment, while observational studies indicate that smokers are more at risk of acute and
chronic pain. We aimed to investigate the association between smoking status and pain sensitivity.
th
Methods: For 10,364 participants in the 6 Tromsø Study, Cox proportional hazard ratios (HR) were
calculated on basis of Cold pressor pain tolerance, and information on smoking status was collected.
Results: 22.1 % of the women and 18.8 % of the men were current smokers, while 38.6 % of women
and 46.8 % of men were previous smokers. Current smokers demonstrated the lowest cold pressor
pain tolerance, prior smokers had intermediate tolerance and individuals with no smoking history
demonstrated highest pain tolerance (Fig 1 and 2, Table1).
[Fig. 1]
[Fig. 2]
HR
95 % CI
P
N
Never
smoked
(ref.)
1
Previous
smokers
1.13
1.04
1.22
0.003
4,416
Current
smokers
1.42
1.30
1.56
0.000
2,121
3,287
10,364
[Table 1. Cold pressor pain tolerance and smoking ]
Conclusion: Both current smoking and previous smoking is associated with significantly attenuated
cold pressor pain tolerance. The results suggest a possible long-term hyperalgesic effect from
nicotine exposure.
Acknowledgements: This work was funded by The Norwegian Research Council, South-Eastern
Norway Regional Health Authority, Northern Norway Regional Health Authority, and The Norwegian
Health Association.
383
ANALIZE AN EPIDEMIOLOGICAL DATA OF THE CHRONIC PAIN POPULATION BY EDUCATED
GP ON CHRONIC PAIN IN BH
1
A. Karkin-Tais , S. Marić
2
1
2
Pain Department, Eurofarm Polyclinic Centre, Clinical Center RS, Sarajevo, Bosnia-Herzegovina
Background and aims: Goal is to improve the knowledge of GP on chronic pain through educational
courses.
Another goal is through interview and questions, analize an epidemiological data on chronic pain.
Methods: Courses are held at 5 Canton
Participants: GP and other specialists, every group made 15-35.
Topics: Chronic Pain and Sip.
Content of courses: Workshops, case study and interactive knowledge test. Test includes questions to
test knowledge.
Statistic methodology was based on the analysis of data questionnaires on the sample of 500 chronic
pain population. The questionnaire contained 40 questions about the intensity of pain (VAS),
diagnosis, treatment, impact of pain on various aspects of life, and other parameters.
Results: Test of knowledge.
Chronic pain in sample: prevalence of chronic pain was 32, 53%.
In age 50 -70, pain prevalence was 75%, higher in females 62%.
Pain intensity, moderate and severe was in two thirds, 76%.
Pain impact on various aspects of life (VAS 0-10) - impact index: two-thirds were hampered moving,
depressed and with disturbed relationships with others.
Conclusions: The presence of high-intensity pain and poor quality of life BH population requires to
continue education on chronic pain and research.
384
SMOKING AS A RISK FACTOR FOR CHRONIC MUSCULOSKELETAL COMPLAINTS IS
INFLUENCED BY AGE. THE HUNT STUDY
1
2
3,4
S. Kvalheim , I. Sandven , K. Hagen , J.-A. Zwart
1
5,6
2
Neurology, Oslo University Hospital, Department of Biostatistics and Epidemiology, Oslo University
3
Hospital (OUS), Ullevål, Oslo, Department of Neuroscience, Faculty of Medicine, Norwegian
4
University of Science and Technology, Norwegian National Headache Centre, Section of Neurology,
5
6
St.Olavs Hospital, Trondheim, Institute of Clinical Medicine, University of Oslo, Department of
Neurology and FORMI, Oslo University Hospital, Oslo, Norway
Background: Chronic musculoskeletal complaints (MSCs) are among the major health problems, and
cross-sectional studies suggest an association between smoking and MSCs. The present study is
designed to assess the association between smoking and chronic MSCs and is based on data from a
large longitudinal cohort study of all inhabitants ³20 years in Nord-Trøndelag County (Helse
Undersøkelsen i Nord-Trøndelag -HUNT).
Material and method: The study population consisted of 15,134 subjects without chronic MSCs and
valid exposure data on smoking at baseline (HUNT 2). The outcome was defined as presence of
chronic MSCs at follow-up (HUNT 3). The Poisson regression model was used to estimate the
incident rate ratio (IRR).
Results: Smoking at baseline represents a 20% increased risk (IRR=1.20, 95% CI: 1.14 - 1.27,
p=0.0001) for chronic MSCs at follow-up. The risk for chronic MSCs by daily smoking decreased with
increasing age up to 50 years, which after there was no significant association.
Conclusion: Daily smoking represents a 20 % increased risk of chronic MSCs in persons younger
than 50 years. Modifiable risk factors like smoking should be included in public health intervention
programs for MSCs.
Acknowledgments: The Nord-Trøndelag Health Study (The HUNT Study) is a collaboration between
HUNT Research Centre, Faculty of Medicine, Norwegian University of Science and Technology
(NTNU, Verdal), Norwegian Institute of Public Health, and Nord-Trøndelag County Council.
The study was supported by a grant from the EXTRA funds from the Norwegian Foundation for Health
and Rehabilitation through the Norwegian Low Back Pain Association.
385
CHARACTERISTCS OF THE ADULT POPULATION WHO ATTEND CENTRES OF PAIN CLINIC IN
ITALY
1
2
3
3
4
5
3
R. Latina , M.G. De Marinis , M.S. Cattaruzza , J. Sansoni , A. Gatti , E. Di Biagio , A. Camilloni , P.
6
7
8
9
9
3
Notaro , V. Guzzetti , D. D'Angelo , C. Mastroianni , G. Casale , G. Tarsitani , AND Pain Clinic Group
in the Lazio Region, Italy
1
2
Public Health Department, Sapienza University, Rome, Nursing Department, Campus Bio-Medico
3
4
University, Public Health Department, Sapienza University, Emergency Medicine and Pain
5
6
Department, Tor Vergata University, Dental Clinics, Private Clinic, Roma, Transplantation
7
8
Department, Niguarda Ca' Granda Hospital, NoPain Onlus, Milan, Public Health Department, Tor
9
Vergata University, Palliative Care, Antea, Roma, Italy
Background and aims: The treatment of pain makes use of a multidisciplinary approach that may be
validated through the network of pain clinics (Law 38/2010). They supply different levels of complex
assistance (Hub-Spoke). Many citizens, suffering from benign chronic pain about which little is known,
turn to these centres. The aim of this study is to describe the socio-demographic and clinical
characteristics of the adult population who attend these pain centres.
Methods: A study of several pain therapy centres has been carried out with respect to Lazio Regions
of Italy. The data compiled comprises those persons who have been suffering from benign chronic
pain for at least six months, excluding headache, and refers to the working population ( aged18-71 ),
as well as to the treatments proffered. The data has been assembled in an SPSS database and
elaborated.
Results: 1171 patients were recruited, 32.7% males and 67.3% females (p = .0689). The most
representative age in the collected data is 60-65, regarding both sexes (34%). 34% of the patients
suffer intense pains, 26% moderate pain, and 20% minor or no pain, with a missing factor of 20%.
The male/female relation = .1830. The pain is nociceptive (48.4%), neuropathic (16.7%), visceral
(0.7%), mixed (29.4).
Conclusions: The present study suggest that females rather than males generally use centres of
pain therapy, and there is increased use with advancing age, and which is of moderate to serious
intensity. Even after the promulagation of Law 38/2010, there remains the trend not to measure pain.
386
PREVALENCE AND COMORBIDITY OF PAIN SYMPTOMS IN THE GENERAL POPULATION
1
2
2
2
L. Ligthart , C.M. Visscher , C.M.H.H. van Houtem , A. de Jongh , D.I. Boomsma
1
1
2
VU University Amsterdam, Academic Center for Dentistry Amsterdam (ACTA), Amsterdam, The
Netherlands
Background and aims: The prevalence of individual pain disorders has often been studied, but few
studies investigate many different pain types at once. We aimed to investigate how different pain
types relate to each other and to comorbid traits, especially anxiety and depression, in the general
population.
Methods: We analyzed data from a large population-based cohort of Dutch twin families (11.530
subjects). Pain was assessed in eight body sites: back, neck, head, abdomen, joints, chest, teeth and
face. The Graded Chronic Pain Scale (von Korff, 1993) was used to assess the pain intensity and
disability. Anxious depression was measured with a subscale of the Adult Self Report (Achenbach,
1997).
Results: All pain types except chest pain and toothache were more common in women than in men.
Women were also more likely to report chronic pain. The prevalence of most pain types was relatively
similar across age, except for headache and abdominal pain, which decreased, and joint pain, which
strongly increased with age (with 4% and 17% chronic joint pain in the youngest and oldest age
groups, respectively). Strong and consistent comorbidity was observed: having any type of pain was
associated with an increased risk of any other type of pain (correlations between 0.1 and 0.7), as well
as anxious depression.
Conclusions: Chronic pain is very common in the adult Dutch population (21%). We observed strong
comorbidity of different pain symptoms and anxious depression. Given the severe disability caused by
these conditions, research into the causes of this comorbidity is warranted.
387
PREVALENCE OF PERSISTENT PAIN IN PSYCHIATRIC OUTPATIENTS
1
2
I. Løvås , C.S. Nielsen , A. Woodhouse
3
1
Tiller DPS, St.Olav`s Hospital, Trondheim, NTNU - Norwegian University of Science and Technology,
2
Faculty of Medicine, Dep of Community Medicine and General Practice, Trondheim, Division of
3
Mental Health, Norwegian Institute of Public Health, Oslo, National Competence Centre for Complex
Symptom Disorders, St. Olav`s Hospital, Trondheim, NTNU - Norwegian University of Science and
Technology, Faculty of Medicine, Dep of Community Medicine and General Practice, Trondheim,
Norway
Background and aims: Patients with psychiatric disorders often describe pain symptoms. Studies on
pain prevalence in general psychiatric populations are limited, whereas some specific disorders are
well documented. Several studies describe persistent pain in general populations and psychiatric
disorders in pain populations. The existing literature varies in methodology and conduct. The aim of
this study was to investigate prevalence and characteristics of persistent pain ≥6 months (PP) in
psychiatric outpatients in relation to age, gender and psychiatric disorder.
Methods: A descriptive cross sectional survey was performed in outpatient-clinics at a Community
Mental Health Centre in Norway. Clinicians invited patients to participate when meeting them for
treatment sessions. The eligible number of patients was 438. The self-report questionnaire contained
questions of demographics, pain characteristics and management. Descriptive statistics were
performed.
Results: Response rate was 43% (n=190). 76% reported PP of whom 47% reported moderate/severe
intensity. Prevalence of PP increased with higher age. Females reported higher prevalence of PP
compared to males but not significantly. Mean duration of pain was 11.3years/SD 9.82. Highest rate
of PP was found in PTSD (91%), anxiety disorders (89%) and personality disorders (82%). The most
common pain management was physiotherapy, and the use of pain medication was modest.
Conclusion: Compared to the general population, prevalence of PP is high in this population of
psychiatric outpatients. This has important implications for providers of psychiatric health care
services.
388
FEMALE CHRONIC PELVIC PAIN IS HIGHLY PREVALENT IN DENMARK. A RANDOMLY
SELECTED CROSS-SECTIONAL STUDY
1
2
3
S. Loving , T. Thomsen , P. Jaszczak , J. Nordling
1
4
2
Multidisciplinary Pain Centre, Herlev Hospital, University of Copenhagen, Herlev, Abdominal Centre,
3
Rigshospitalet, Copenhagen University Hospital, Copenhagen Ø, Department of Gynaecology,
4
Department of Urology, Herlev Hospital, University of Copenhagen, Herlev, Denmark
Background and aim: Female chronic pelvic pain [CPP] is a highly prevalent (2-24%) clinical
problem with substantial burden on the health care services. We aimed to examine prevalence,
characteristics, and risk factors for CPP in Danish women, and to compare these findings with painfree controls.
Methods: A cross-sectional postal survey of the prevalence of CPP was undertaken in a randomly
selected general female population in Denmark (N=2500) between November 2010 and April 2011.
Inclusion criteria were: a. female, b.≥ 18 years of age. Statistical analyses included prevalence
percentage rates, chi-square tests, Mann-Whitney tests, unpaired T- tests, and multiple regression
analyses.
Results: 1179 women responded. 130 (11%) women reported CPP ≥ 6 months. The highest
prevalence was observed in women aged ≤ 25 years (17%), and between 46-55 years (17%).
Average pain intensity reported was 4 [IQR 2-6] on a Numerical Rating Scale [NRS]. 61 (5.2%)
women experienced at least moderate average pain intensity (NRS ≥ 4). Potential risk factors for CPP
were age, country of birth, self-reported pelvic diseases, and former pelvic trauma or surgery (p <
0.05). No association was found between CPP and selected socioeconomic factors (residence area,
education, occupation, and cohabitation).
Discussion and conclusion: Although the reported prevalence is based on 48% of the invited
sample, drop-out analyses found that respondents did not deviate from non-respondents. Therefore,
we considered the reported 11% prevalence rate representative for the total sample and
generalisable to the general female population in Denmark.
389
NEUROPATHIC PAIN IN PATIENTS WITH SPINAL CORD INJURY: A RETROSPECTIVE STUDY
1
2
1
1
1
S. Milicevic , A. Karadzov Nikolic , R. Babovic , A. Sekulic , S. Stevanovic , V. Piscevic
1
3
2
Clinic for Rehabilitation Dr M. Zotovic, Special Hospital for Cerebral Palsy and Developmental
3
Neurology, Department of PRM, KBC Zvezdara, Belgrade, Serbia
Background: Most people with a spinal cord injury (SCI) rate neuropathic pain as one of the most
difficult problems to manage and there are no medical treatments that provide satisfactory pain relief
in most people.
Aim: To investigate the prevalence of chronic and neuropathic pain in patients with SCI.
Methods: A retrospective study of 419 patients with the SCI treated to the Clinic for rehabilitation “Dr
M. Zotovic”, Belgrade, Serbia, from January 2000 to December 2009. To asses pain intensity was
used Visual analog scale (VAS), for evaluation a neuropathic pain was used Pain detect. The
presence of pain were registered on admission, during functional rehabilitation and at the discharge.
The level of statistical significance in our study was set to 0.05.
Results: In the total number of patients, 278 (66.34%) have a chronic pain. In 85% of them, pain was
below the level of SCI and in 15% of them pain was at the level of SCI. 83% of patients with chronic
pain fulfilled Pain detect score for neuropathic pain. The average age of patients in the study was 45.5
± 16.8 years. 269 (64.2%) patients had traumatic and 150(35.8%) patients had non-traumatic spinal
cord injury. ASIA A lesions was predominant (43.2%), followed by ASIA C (36.3%) and ASIA B
(20.5%). The cervical spinal cord injury had 174 (41.5%) patients, thoracic 182(43.4%) and lumbar
injury had 63(15%) patients.
Conclusion: Neuropathic pain following SCI represents a significant medical problem, and there is a
need for more effective treatments.
390
FACTORS ASSOCIATED WITH PAIN PERSISTENCE IN PATIENTS WITH MAJOR DEPRESSIVE
DISORDER DURING A 6-MONTH FOLLOW-UP PERIOD
1
1
2
3
4
J. Hong , D. Novick , W. Montgomery , H. Dueñas , X. Peng , J.M. Haro
1
2
5
3
Eli Lilly and Company, Windlesham, UK, Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia, Eli
4
5
Lilly de Mexico, Mexico City, Mexico, Eli Lilly and Company, Indianapolis, IN, USA, Parc Sanitari
Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona,
Spain
Background and aims: Patients with major depressive disorder (MDD) frequently suffer from
concomitant pain symptoms, which may negatively influence the prognosis of depression. This study
examined factors associated with pain persistence in patients with MDD.
Methods: Data in this post hoc analysis were taken from a 6-month prospective, non-interventional,
observational study that involved 1,549 MDD patients without sexual dysfunction at baseline in twelve
countries worldwide. Pain was measured using the pain-related items of the Somatic Symptom
Inventory. Logistic regression was used to examine the baseline predictors of pain persistence (vs.
remitted pain) during follow-up among patients who presented with pain at baseline.
Results: Of the 1,117 patients analysed, 52% (n=576) had pain at baseline. Of these, 11%
persistently suffered from pain during the 6-month follow-up. Being older (Odds ratio (OR)=1.04,
p=0.015) and having a higher pain severity at baseline (OR=1.12, p=0.015) were associated with
persistent pain, while living in Mexico (vs. Middle East) (OR=0.36, p=0.033), living with a
spouse/partner (OR=0.48, p=0.047), having a positive sexual experience in the past week (OR=0.38,
p=0.022), and initiation of treatment with duloxetine (vs. a selective serotonin reuptake inhibitor
(SSRI)) (OR=0.13, p< 0.001) were associated with remitted pain.
Conclusions: About one in ten patients with depression who had pain at baseline persistently
suffered from pain symptoms during 6 months. Patients who were older, living in Middle East, not
initiated on duloxetine, had no recent sexual satisfaction, and were not living with a spouse/partner
were at increased risk of suffering from persistent pain during follow-up.
391
HOW TO ASK CHIDLREN ABOUT THEIR PAIN
S. O'Higgins
Centre for Pain Research, National Unversity of Ireland, Galway, Ireland
Background and aims: PRIME C aims to identifying the extent of chronic pain among children living
in Ireland by developing an effective survey instrument for use with 5-12 year olds. Through a cycle of
pilots, children's perceptions and understanding of internationally standardised reliable and valid
measures used with adolescents were explored. Attention being paid to both item construction and
questionnaire design, advocated in seminal works on data collection, ensures that tools embody the
purpose of the research.
Method: One-to-one interviews with children over a 3 month period were conducted. These continued
until there was no discrepancy between adults' and the understanding of children on the items being
used. Interviews were recorded and transcribed verbatim prior to analysis.
Results: Extensive piloting gave insights from the children's comments, ideas and perceptions of the
questions they were being asked. The first round explored the words within each item; understanding
of some words proved to be very different from that of the adult researchers. Following each round
changes were made based on the ideas given by the children. More children examined the instrument
to ensure that items were understandable and format user friendly.
Conclusion: The insights gained from the children's comments, ideas and perceptions of the words
used prompted changes to both language and layout of the survey instrument. In order that surveys
with children actually measure that which is under investigation it is vital that children's
understandings of the language being used are examined, prior to entry into the field.
392
NEUROTICISM AND PAIN CATASTROPHIZING, PERSONALITY CONSTRUCTS PREDICTIVE OF
PAIN PERCEPTION
1
2
2
1
A. Banozic , A. Miljkovic , I. Kolcic , L. Puljak , O. Polasek
1
2
2
Department of Anatomy, Histology and Embryology, Department of Public Health, University of Split,
School of Medicine, Split, Croatia
Background and aims: Considerable research has demonstrated the role of psychological and
contextual variables in pain perception, but limited data is available on the contribution of personality
traits in response to the acute pain in a healthy population. Thus we aimed to examine the
associations between pain perception, personality constructs (neuroticism, psychoticism, and
extroversion) and pain catastrophizing in 401 pain-free adults.
Methods: Two cohorts from the island of Korcula (N=121) and mainland city of Split (N=280)
participated in the study. Prior to pain pressure measurements (pain tolerance (PTOL) and
threshold(PPT)) participants completed a set of questionnaires: short version of Eysenck Personality
Questionnaire - Revised (EPQ-R) and Pain Catastrophizing Scale (PCS).
Results: PTOL and PPT significantly differed between Korcula and Split cohort. Multivariate analysis
revealed higher PPT and increased PTOL time for mainland cohort and a consistent sex difference
(men had higher threshold and increased tolerance). Personality constructs and PCS were
significantly associated, while neuroticism was the only one associated to pain measurements in both
cohorts. Higher PCS was found in island population while men and women differed only in
neuroticism. Regression analysis also revealed neuroticism as the only significant predictor of PTOL
and PPT in both cohorts.
Conclusions: These results suggest that in healthy population, particularly women, neuroticism
proved to be associated with perception of pain. Environmental factors should be also considered in
the light of increased catastrophizing scores of island population, possibly suggesting catastrophizing
to be a dispositional as well as situational construct.
393
PAIN AND EMOTIONAL CHARACTERISTICS IN LONG TERM FOLLOW UP PATIENTS AFTER
SURGERY FOR BREAST CANCER
1
2
3
4
S. Ramaswamy , D. Sheridan , D. Gillanders , M. Fallon , L. Colvin
1
5
2
Pain Clinic, Charing Cross Hospital, London, School of Molecular and Clinical Medicine, University
3
4
of Edinburgh, School of Health in Social Science, Palliative Medicine, University of Edinburgh,
5
Consultant, Department of Anaesthesia, Critical Care and Pain Medicine, Western General Hospital,
Edinburgh, UK
Background and aims: Persistent pain after breast cancer treatment (PPBCT) is a common sequel
following breast cancer treatment.
The aims of this cross-sectional, questionnaire-based study were to examine the emotional
characteristics and assess the risk factors and severity of pain in patients with PPBCT in long-term
breast cancer patients.
Methods: After ethical committee approval, long-term breast cancer patients were invited to complete
a questionnaire. This recorded information on their treatment, demographic data, presence of PPBCT
and the Hospital Anxiety Depression Scale (HADS). Patient with PPBCT completed further questions
including Self-reported Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), Chronic
Pain Acceptance Questionnaire (CPAQ) and questions about the nature of their pain. Results were
analysed using appropriate statistical tests.
Results: A total of 402 patients completed the questionnaire. Mean age was 63.5±10.72 years. 115
(28.6%) patients reported on-going chronic pain. In patients with pain, mean VAS was 3.4±2.44.
35.7% (41/115) had a VAS≥4. 37% (35/95 patients) had S-LANNS ≥12 suggesting neuropathic pain.
Patients with pain were significantly younger (64.58±10.49 vs 61.06±10.91 years; p= 0.004) and had
significantly greater HADA (6.18±4.29 vs 4.54±3.9; p=0.001), HADD (3.57±3.08 vs 2.41±2.8;
p=0.0001) and total HADS (9.79±6.54 vs 6.94±6.05; p=0.0001). Increased VAS score was associated
with increased HADA (t93=-6.541; p=0.0001) and total HADS (t91=-10.267; p=0.0001). S-LANSS ≥12
was not associated with increased HADS but was associated with lower CPAQ scores (t 46=2.727;
p=0.009).
Conclusions: Significant numbers of women suffer from PPBCT and were associated with
significantly higher anxiety and depression scores.
394
PECULIARITIES OF PAIN IN WOMEN WITH INFERTILITY
1
I. Romanenko , I. Romanenko
1
2
2
Lugansk State Regional Hospital, Lugansk State Medical University, Lugansk, Ukraine
Introduction: Infertility in marriage is one of the most important and complex medical and social
problems. Infertile women often complain on pain of different localization.
The aim of the work was to study the clinical features of pain of different localization and intensity in
women with endocrine infertility.
Methods: Fifty four women with infertility of endocrine etiology were studied. Data of gynecological
and extragenital history, transvaginal sonography was analyzed. Experimental psychological methods
included Spielberger State and Trait Anxiety Inventory, Beck's Depression Inventory, McGill Pain
Questionnaire, Visual Analogue Scale (VAS).
Results: Recurrent headaches was found in 59.3% of women, neck pain - in 14.8%, toracalgia - in
20.3%, low back pain - in 31.5%. Most often women were bothered by pain in the thoracic and lumbar
spine (58.1%). Pain in the abdomen was found in 46.3% of women, combination of pain in the spine
and abdomen - in 27.8%, pain in joints - in 13%, cardialgia - in 16.7%.
Intensity of pain in the most of the patients (67.4%) was moderate and in 32.6% - mild. Average
intensity of the headache on VAS was 4.8 points, abdominal pain - 4.4, back pain - 2.9, cardialgia 3.8.
Conclusions: The study showed frequent combination (96.3%) of endocrine infertility and pain of
different origin, nature and localization. This should be reflected in the formulation of clinical
diagnosis. Such patients require detailed complex examination and comprehensive approach to
treatment, which will contribute to the improvement of mental and physical status and quality of life.
395
CHRONIC PAIN IN MULTIMORBID INPATIENTS: WHAT IS THE DIFFERENCE? A
RETROSPECTIVE PILOT-STUDY
1
1
1
1
2
3
1
D. Schneider , L. Zimmerli , A. Kienast , K. Siebenhuener , C.E. Minder , R. Saller , E. Battegay , E.
4
4
1
Eschmann , J. Blaser , B.M. Holzer
1
2
3
4
Division of Internal Medicine, Horton Center, Institute of Complementary Medicine, Research
Center for Medical Informatics, University Hospital Zurich, Zurich, Switzerland
Background and aims: Multimorbidity (defined as having two or more concurrent chronic medical
conditions) is frequent in the elderly population with a prevalence of about two third. Despite its
frequency, little is known about the occurrence of chronic pain in this patient group. The aim of the
study was to identify and analyze multimorbid inpatients with chronic pain.
Methods: We conducted a retrospective study of medical records, including all multimorbid inpatients
of the Division of Internal Medicine in 2011 (n=1139). Data were extracted from electronic medical
records of the University Hospital Zurich and individually reviewed by the research team.
Results: Multimorbidity occurred in 87% of the recorded internal inpatients in 2011. Prevalence of
chronic pain in multimorbid patients was 38%. Mean age was 65.7 (SD 15.8), 51% were males. This
patient group had on average 6.6 chronic diagnoses (SD 2.9) and significantly more than multimorbid
patients without pain (5.1, SD 2.4; p< 0.0001). 60% of those had one pain diagnosis, 27% had two
and 13% more than two. Depressive disorders were twice as high in chronic pain patients as in
multimorbid patients without pain. Multimorbid chronic pain patients spent significantly more days in
hospital than multimorbid patients without chronic pain (p< 0.0007).
Conclusions: More than every third multimorbid inpatient had chronic pain. Due to the high number
of concurrent chronic conditions the treatment and management of chronic pain in this patient group
needs to be reconsidered.
Acknowledgements: We thank Mundipharma Medical Company for sponsoring this study.
396
THE PREVALENCE OF PAIN IN EMERGENCY DEPARTMENT OF UNIVERSITY HOSPITAL
1
2
2
A. Sciupokas , J. Salkauskaite , S. Musnickaite , E. Kaktyte
1
2
2
Neurology, Lithuanian University of Health Sciences, Kaunas, Lithuania
Background: Pain is the most common reason for people to seek health care and accounts for more
than two-thirds of visits to the emergency department (ED).
Aim: The purpose of this study was to determine the prevalence of pain in the ED of university
hospital and to classify pain location, pain etiology, pain intensity, and discharge outcomes.
Materials and methods: We conducted a cross-sectional 7-day repeated study of all patients
admitted to the ED. All ED charts were investigated, and the word “pain” or pain equivalent word
recorded. Two categories of pain were defined: chief complaint of pain, any pain. Pain location was
defined according IASP taxonomy, pain etiology - by generally accepted principles. Pain scales use
rate was calculated. Discharge outcomes were defined either outpatient or inpatient.
Results: Charts from 922 ED visits during double 7-day period were reviewed. 576 patients (62.5%)
had pain documented, and to 304 (52.8%) of them pain was the chief complaint. The patients
specified 714 pain locations, and head (35.9%), abdomen (18.2%), lower extremities (12.5%) were
most frequent. Therapeutic pathology (47.1%) prevailed trauma (40.3%). Numeric pain scale use rate
was 0.67. Pain patients were discharged as outpatients in 451 (78.3%) cases, 13.7% have been
referred to medical wards, 8.7% - to surgery.
Conclusion: More than three fifths of all visits to the ED were related to pain, and more than half of
these patients indicated pain as chief complaint. Almost four fifths of all pain patients were discharged
to outpatient care.
397
EXPLORING AND EXPLAINING THE RELATIONSHIP BETWEEN CHRONIC PAIN, DEPRESSION
AND SMOKING STATUS IN A LARGE GENERAL POPULATION-BASED COHORT
O. van Hecke, N. Torrance, B.H. Smith
Population Health Science, University of Dundee, Dundee, UK
Background: Most studies show that the smoking rate in pain populations is higher than the general
population and that smokers report greater pain intensity and worse functioning. Evidence from
specialised pain clinics suggests that depression may act as mediating factor in helping to explain the
relationship between smoking and chronic pain. This study explored the relationship in a large general
population-based cohort.
Methods: Data were obtained from Generation Scotland: the Scottish Family Health Study
(GS:SFHS). Presence and severity of chronic pain, self-reported smoking status, and a positive
Structured Clinical Interview for DSM-IV disorders as evidence of current or past major depressive
disorder (MDD) were analysed.
Results: Of all 24,042 participants, 8,436 (36%) reported any chronic pain. 19.1% (n=1,615) were
current smokers, 47.9% (n=4,043) never-smokers and 33% (n=2,778) former smokers. 16% (n=
1,348) also had a history of current or past MDD. A multivariate analysis of covariance [smoking
status, age, gender, education, Scottish Index of Multiple Deprivation (SIMD)] showed that current
smokers demonstrated higher mean pain intensity and -disability scores compared with former and
non-smokers (p< 0.001 for all analyses). After controlling for depression in a statistical mediation
model, a history of depression emerged as mediator for pain intensity but not smoking-related pain
disability.
Conclusions: A history of current or past MDD mediated the relationship between smoking and pain
intensity but not pain-related disability. It appears that smokers with chronic pain in the general
population are different in this regard from smokers being treated in pain clinics.
398
CHILDHOOD TRAUMA, ADULT PSYCHOLOGICAL STATUS AND PAIN: A CONDITIONAL
PROCESS ANALYSIS
1
1
2
2
A.D. Woodward , P. Campbell , F. Creed , B. Tomenson , J. McBeth
1
1
2
Primary Care Sciences, Keele University, Newcastle Under Lyme, Manchester University,
Manchester, UK
Background and aim: Psychological stress is a robust predictor of pain at multiple sites. This study
tested the hypothesis that the relationship between stress and pain at multiple sites would be
mediated by adult attachment style and moderated by childhood abuse.
Methods: In a population-based cross-sectional postal survey 1443 adults aged 25-65 years provided
data on psychological stress (anxiety, depression, somatic symptoms, threatening life events), the
presence of pain (number of sites, range 0-29), adult attachment style, and childhood abuse.
Structural equation modelling tested the association between psychological stress and the number of
pain sites (the direct effect), adjusted for age, and the mediating effect of attachment style (the
indirect effect). Multiple-group analysis tested the moderating effects of childhood abuse. Results are
2
presented as standardised regression weights (β) with p values and variance explained (R ). Root
mean square error of approximation (RMSEA) assessed model fit.
Results: Higher levels of psychological stress were associated with a higher number of pain sites
2
(direct effect β=0.52, p=0.001, R =26%) and this relationship was mediated by secure attachment
style (indirect effect β=-0.022, p=0.000). 335 (23%) participants reported frequent childhood abuse.
Abuse status moderated the relationship: frequent abuse direct effect β=0.58 p=0.001, indirect effect
β=-0.025, p=0.000; no abuse direct effect β=0.46 p=0.001, indirect effect β=-0.008, p=0.166. The
model adequately fit the data (RMSEA=0.037).
Conclusion: Treatments targeting attachment style may be effective for individuals with pain at
multiple sites and a history of frequent childhood abuse.
399
IMPLEMENTATION OF CLINICAL PRACTICE GUIDELINES AND PATIENT REPORTED
OUTCOMES: PRELIMINARY DATA FROM PAIN OUT, AN INTERNATIONAL ACUTE PAIN
REGISTRY
1
2
1
R. Zaslansky , C.R. Chapman , W. Meissner , PAIN OUT Collaboration
1
2
Jena University Hospital, Jena, Germany, Anesthesiology, University of Utah, Salt Lake City, UT,
USA
Background and aims: Clinical practice guidelines (CPGs) are a synthesize of the best available
evidence, aim to assist practitioners in making informed decisions about treatments and to improve
patient outcomes. We assessed whether adherence to two practices recommended for all patients
undergoing surgery would result in improved patient reported outcomes (PROs) in a heterogeneous
patient population.
Methods: 6347 adult patients undergoing orthopaedic or general surgery, in 11 medical centres in
Europe and Israel, provided PROs by filling in the validated International Pain Outcomes
questionnaire on the first day after surgery, as part of PAIN OUT, an international acute pain registry,
established with funds from European Commission's FP7 Program. The practices assessed included:
(1) asking patients if they received information about pain treatment options;
(2) determining if nursing staff recorded intensity of pain in the medical record.
Results: 65% of patients (4009/6155) (range by site 27 - 85%) reported they received information
about pain treatment options. 76% of patients (4668/6142) (range 0.3 - 99.8%) had their pain
assessed and recorded. Only one PRO, 'allowed to participate in decisions about your pain treatment
as much as you wanted' showed a large effect size for 'provision of information'.Recording pain did
not improve PROs for intensity of pain, side effects or perception of treatment.
Conclusions: These preliminary results indicate that CPGs-derived recommendations do not easily
transfer to a heterogeneous patient population. Further work is required to assess the discrepancy
between implementation of CPG-derived recommendations and lack of effect on PROs.
400
HEART RATE VARIABILITY BASED INDEX FOR PAIN ASSESSMENT IN CHILDREN
J. Avez-Couturier , J. De Jonckheere , M. Jeanne , L. Vallée , R. Logier
1,2
2
2,3
2
1
3
2
1
Paediatric Neurology, CHRU de Lille, Lille Cedex, CIC-IT 807 CHRU Lille, Anaesthesia and
Intensive Care, CHRU de Lille, Lille, France
Background and aims: Children pain assessment is usually performed through self report or
behavioural scales. However, such measures give subjective and punctual information. We have
previously described a non-invasive, continuous and objective antinociception / nociception balance
measurement index based on heart rate variability analysis: the analgesia-nociception index (ANI)
TM
(Physiodoloris ; Metrodoloris, Loos, France). During general anaesthesia, we showed that ANI
decreased significantly during painful stimulations (Jeanne, 2009). The aim of this study was to
evaluate ANI ability to detect procedural pain in conscious children.
Methods: prospective, non-interventional study in children undergoing muscular biopsy with
analgesia and sedation. Medical staff was blind to the ANI monitor, in order not to affect their
decisions for pain management. ANI was calculated for 300 seconds periods: T1, before local
anaesthesia; T2, after local anaesthesia; T3, before incision; T4, after incision. Pain was assessed by
the rFLACC scale (Malviya, 2006) at T4. Results were compared by Wilcoxon's test.
Results: 26 children were included (mean age 6, 0.5-16; 16 males). ANI decreased significantly after
noxious stimulation, among T1-T2 (p=0.011), and T3-T4 (p=0.005). At T4, ANI discriminated painful
children (rFLACC≥4/10) with a 0.76 area under ROC curve.
Conclusion: ANI decreased significantly after noxious stimulation on sedated children. ANI could be
a relevant tool to assess nociception in children, continuously and non-invasively. Further studies on
larger population are needed to confirm these results and to determine thresholds.
401
CUT-OFF POINTS FOR MILD, MODERATE AND SEVERE PAIN ON THE VAS FOR PAIN FOR
PATIENTS WITH CHRONIC MUSCULOSKELETAL PAIN
1
1
2
A.M. Boonstra , G.A. Balk , H.R. Schiphorst Preuper , R.E. Stewart
1
3
2
Rehabilitation Center 'Revalidatie Friesland', Beetsterzwaag, Department of Rehabilitation, Center
3
for Rehabilitation, Department of Health Sciences, Community & Occupational Medicine, University
Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Objectives: The aim of our study was to find the cut-off points on the VAS to distinguish between
mild, moderate and severe pain, firstly in relation to pain-related interference with functioning,
secondly in relation to the verbal description of the VAS scores and thirdly by latent class analysis for
patients with chronic musculoskeletal pain.
Methods: 456 patients were included. Pain was assessed using the Visual Analogue Scale (VAS)
and Verbal Rating Scale (VRS); functioning was assessed using the domains of the SF-36. Eight cutoff point schemes were tested using MANOVA, ordinal logistic regression and latent class analysis.
Results: The study showed that VAS scores ≤3.4 corresponded to mild interference with functioning,
while 3.5 - 6.4 implied moderate interference and ≥6.5 implied severe interference. VAS scores ≤3.4
were best described for patients with chronic musculoskeletal pain as ' mild pain' , 3.5 - 7.4 as '
moderate pain' and ≥7.5 as ' severe pain'. The latent class analysis found that a three-class solution
fittest best, resulting in the classes 0.1 - 3.8, 3.9 - 5.7 and 5.8 - 10 cm.
Discussion: The findings of our study agree with those of some other studies, although many other
studies found different optimal cut-off point schemes.
402
CADI STUDY: CHARACTERISTICS OF BREAKTHROUGH PAIN IN PATIENTS WITH
PERSISTENT CHRONIC PAIN TREATED WITH OPIOIDS
J.P. Cajaraville
Clinica Universidad de Navarra, Pamplona, Spain
Aim of investigation: Breakthrough pain (BTP) characteristics and response to treatment in patients
with chronic pain may vary, and these differences may be responsible for an inadequate adherence to
the therapeutic treatment. A better knowledge of the characteristics between different BTP episodes
in the same patient may help to optimise treatment selection, improving patient adherence and,
overall, the quality of life of these patients. The aim of the study was to evaluate variability of intensity,
duration and type of BTP episodes in patients with persistent chronic pain controlled with opioids,
based on records that patients will complete during their episodes of BTP.
Methods: Observational and prospective (1 month follow-up) spanish multicenter study involving
patients with chronic cancer and non-cancer pain controlled with opioids and presenting breakthrough
pain episodes. Each patient received a Patient´s Record, where the clinical characteristics of
breakthrough pain episodes will be recorded.
Results: Data were obtained from 50 patients (23 oncologic and 27 non-oncologic, mean age of 61.1
years, 62% females). No statistically significant differences were observed between oncologic and
non oncologic patients in maximum pain intensity, pain relief or pain durability of the episodes. For all
three parameters, inter-patient variability was higher than the intra-patient variability throughout the
episodes. However the intra-patient coefficients of variation were high for pain intensity at the end of
the crisis, the total pain relief and time to rescue medication.
Conclusions: Although inter-patient variability is higher, the intra-patient variability is important
enough to take it into account in optimizing treatment selection.
403
QUALITY OF SLEEP IN PATIENTS ATTENDING CHRONIC PAIN CLINIC
1
2
3
V. Gadiyar , J. Williams , K.K. Kataria , N. Raj
1
2
3
3
Anaesthesia and Pain Management, Anaesthesia, Pennine Acute Hospitals NHS Trust,
Manchester, UK
Background and aim: 'Sleep quality' is important due to complaints such as difficulty falling asleep or
maintaining sleep. Poor sleep quality can lead to medical disorders including chronic pain(1). Our aim
was to measure the quality of sleep in patients attending the chronic pain clinic.
Methods: We used The Pittsburgh Sleep Quality Index questionnaire (PSQI)(1).80 consecutive pain
clinic patients filled the PSQI.
Results: Subjective sleep quality is poor in 66% patients, Sleep latency (time taken to fall asleep)is
poor in 70% patients , Sleep duration less than 7 hours in 66% patients, Habitual sleep efficiency
(total number of hours asleep/total number of hours in bed x100) is less than 85% in 81% patients,
Sleep disturbances in 66% patients, Use of sleep medications more than twice a week in 33%
patients, Day time dysfunction in 61% patients. Overall, PSQI scores were poor(less than 5). 74/80
patients (92%) had PSQI scores less than 5 indicating poor quality of sleep.14/80 say that they get
enough sleep. Of these 2/14 (14.2%) take sleeping tablets >once/week.66/80 say that they do not get
enough sleep due to pain. Of these 24/66 (36.4%) take sleeping tablets >once/week.
Conclusion: Eventhough 66% indicate poor quality of sleep subjectively, global PSQI scores are
much worse at 92%. 32% of the patients admit to taking either prescribed or over the counter
medications to aid sleep. 1.Buysse DJ,ReynoldsIII CF,Monk TH,Berman SR, Kupfer DJ. The
Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Journal of
Psychiatric research 1989;28(2):192-213.
404
QUALITY OF LIFE AND SYMPTOMS IN PATIENTS ADMITTED TO A COMPREHENSIVE
CANCER CENTRE
1,2
3
2
2
4
4
4
G.P. Kurita , C. Niemann , N. Sonne , H. Farholt , U.B. Tange , L. Ankersen , L. Kristensen , L.
2
5
5
4
6
2,7
4
Bendixen , M. Grønvold , M.A. Petersen , M. Nordly , L. Christrup , P. Sjøgren , A. Strömgren
1
2
3
Multidisciplinary Pain Centre, Section of Palliative Medicine, Department of Haematology,
5
Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Department of Palliative
6
Medicine, Bispebjerg Hospital, Copenhagen University Hospital, Dept. Drug Design and
7
Pharmacology, Faculty of Health and Medical Sciences University of Copenhagen, Dept. Clinical
Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
4
Background and aims: Quality of life (QoL) and symptomatology in patients with malignancies
admitted to comprehensive cancer centres are rarely investigated. This study aimed to investigate
QoL and symptoms of inpatients at the departments of haematology and oncology.
Methods: Cross-sectional study, in which 124 cancer inpatients were assessed in May/June 2011.
Inclusion criteria: Age ≥ 18 years. Exclusion criteria: absence at assessments, not able to complete
the questionnaire or unwilling to give informed consent. Demographic data, diagnoses, symptoms,
and health-related quality of life (EORTC QLQ-C30) were assessed. EORTC QLQ-C30 scores were
converted into 0-100. Comparisons were analyzed using Wilcoxon two-sample, rank tests, and
Fisher's exact test.
Results: 124 patients were analysed, mean age = 59y (SD=13.7), 42% admitted to haematological
department (14% had allogenic stem cell transplantation), lung cancer was the most frequent
diagnosis (15%). Role functioning scale was the most severely impaired (mean score=35), whereas
cognitive function showed the best score (mean=70). The mean overall QoL/global health score was
43 (SD=25.6). The symptom burden of the inpatients was strikingly severe and especially fatigue and
appetite loss were pronounced. Role and social functions appeared to be more impaired in oncology
patients than in those admitted to haematology (P=0.0372 and 0.0167, respectively). On the other
hand, pain and constipation were more severely affected in haematology patients (P=0.0194 and
0.0064, respectively).
Conclusions: Inpatients in a comprehensive cancer centre had low quality of life and a severe
symptom burden. Fatigue and appetite loss were the most severe symptoms reported.
405
DID NURSES´ PAIN MANAGEMENT IMPROVE IN LONG-TERM CARE FACILITIES FOR OLDER
RESIDENTS? - RESULTS FROM A GERMAN PRE/POST EVALUATION-PROJECT
N. Schuessler, P. Kutschar, J. Osterbrink
Institute of Nursing Science and Practice, Paracelsus Medical University, Salzburg, Austria
The German National Standard for Pain Management in Nursing recommends items in order to
achieve best nursing practice. According to jurisdictional regulations those are mandatory for nursing
homes. Though in order to meet the requirements and specific demands of chronically ill and/or
cognitively impaired older residents, the standard-criteria have to be modified. In each of 13 homes
taking part in the health services research project "Action Alliance Pain-free City Muenster", a task
force created changes in pain management strategies adjusted to their institutions´ pre-evaluation
results. This presentation will show results of the pre-post-comparison in order to discuss, if pain
management as reported by nursing staff has changed after intervention.
A pre-post-study with non-standardized, nursing home-specific interventions for improvement
strategies was used. The pre-test was conducted from September 2010 to April 2011. After
discussing the results and offering work-shops about pain management a six months intervention
period passed. Since July 2012 nurses of participating nursing homes are again invited to answer the
standardized online-questionnaire designed to assess the extent of the guidelines' and standards'
implementation.
In the pre-test, 149 nurses answered e.g. what kind of assessment tools for observational pain
assessment they knew. 40.7% did not know any observational assessment instrument and 13.8%
stated that there was no such instrument used in their institution. Main topic in task forces which had
between 2 and 9 members was to disseminate knowledge about pain assessment and intervention for
pain relief. We will present post-test results and conclusions after finishing analysis in mid-2013.
406
IMPLEMENTATION OF STANDARDIZED PAIN RATING AND DOCUMENTATION ROUTINES AT
HOSPITALS INWARDS. A SIX MONTH AND TWELVE MONTH FOLLOW UP STUDY
1
1
1,2
A. Peterson , M. Lindblad , B. Gerdle , B. Larsson
1
1,2
2
Pain and Rehabilitation Centre, County Council of Östergötland, Rehabilitation Medicine,
Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University,
Linköping, Sweden
Background: The Pain- and Rehabilitation Centre at the University Hospital in Linköping, Sweden,
provide education for nurses with special interest in pain management; pain representatives. A lack of
systematic pain rating and documentation has been noted. The aim of this project was to implement
uniform and systematic pain rating and documentation at the hospitals of the County Council of
Östergötland, using the Numeric Rating Scale (NRS).
Methods: By educational lectures on standardized pain assessment using the NRS, systematic pain
rating and documentation were implemented in care staff. Encouragement from the pain
representative and continuous information were undertaken to support the compliance. In one survey
in patients (IP) were asked if a standardized pain instrument hade been used and in another survey
staff reviewed pain documentation in medical records (MR). Surveys were conducted prior to the
implementation and followed up 6 months (6-FUP) and 12 months (12-FUP) after the implementation.
Results: Pain was assessed with NRS in 32.6 % (of 285 pain IP) at base line, in 45,9 % (of 157pain
IP) 6-FUP; p-value 0,004, and in 50.6 % (of 81 pain IP); 12-FUP; p-value=0.006.
Pain assessment with NRS was documented in 7.2 % (of 405 MR) at base-line, in 34.5 % (of 229 MR)
6-FUP; p-value < 0.001, and in 35.0 % (of 120 MR) 12-FUP; p-value < 0.001.
Conclusion: One year after implementation, based on education and continuous support from pain
representatives and the project team, increased use of NRS and improved medical record
documentation of NRS was found.
407
DIFFERENT EFFECT OF EXPERIMENTAL ELECTRICAL PAIN ON AUTONOMIC NERVOUS
SYSTEM DERIVED FROM PERIPHERAL PERFUSION INDEX IN HEALTHY VOLUNTEERS
1
1
2
3
1
A. Nakae , T. Nishimura , M. Shibata , T. Mashimo , Y. Fujino
1
2
Anesthesiology and Intensive Care, Pain Medicine, Osaka University Graduate School of Medicine,
3
Suita, Toyonaka Municipal Hospital, Toyonaka, Japan
Backgrounds: Pain is a subjective individual experience, however we should evaluate their pain
status objectively. Pain induces autonomic responses and the pulse oximeter can calculate peripheral
perfusion index(PI), which would be a valuable indicator for nociception. The aim of this study was to
reveal the different autonomic reaction to experimental electrical stimulation in different age and sex
groups.
Methods: Pulse oximeter derived PI and pulse rate(PR) were measured with the maximum tolerable
level of experimental electrical pain using PainVision®. Each four group consists of 16 healthy
volunteers including Male-Young/Old and Female-Young /Old.
Results and Discussion: Pain tolerance was higher in Young-Male than Young-Female (P< 0.01)
and Old-Female (P< 0.05). The paired t-test revealed that the PI was significantly decreased in
Young-Male (P< 0.0001), Young-Female (P< 0.0005), and Old-Male (P< 0.05). The Tukey-Kramer
multiple comparison test showed that the rate of decrease in Young-Male was significantly lower than
in Old-Male (P< 0.0001) and in Old-Female (P< 0.0001). Furthermore, that of decrease in YoungFemale was also significantly lower than in Old-Female (P< 0.001). The stimulation did not affect the
PR. These data suggested that even though the stimulation was so little that it did not influence on
PR, the PI was still able to detect autonomic response to noxious stimulation. The response was
larger in young people than in elderly. Old-Female did not change the PI.
Conclusion: PI is the sensitive indicator to the response to noxious stimuli. However age and sex
should be taken into consideration in analyzing the data.
408
THE SYMPTOM CLUSTER OF "CHRONIC PAIN, FATIGUE, ANXIETY AND DEPRESSION" IN
BREAST CANCER SURVIVORS
1,2
1
I. Schou Bredal , E. Schlichting , T. Warncke
1
3
2
Department of Cancer, Oslo University Hospital, Institute of Health and Society, University of Oslo,
Department of Neurology, Oslo University Hospital, Oslo, Norway
3
Background: A substantial proportion of breast cancer survivors experience chronic symptoms,
including chronic pain, fatigue, anxiety and depression. Chronic pain and fatigue often occur together,
as does chronic pain and depression, as does depression and fatigue. The term symptom cluster is
used to describe three or more concurrent symptoms that are related to each other.
Aim: To investigate the prevalence of fatigue, anxiety and depression among survivors with chronic
pain, and if a symptom cluster of “chronic pain, fatigue, anxiety and depression” exist.
Methods: Women (N=834), treated for early-stage breast cancer two to six years ago completed the
Brief Pain Inventory Questionnaire, the Fatigue Questionnaire, the Hospital Anxiety and Depression
scale. Chi-square and Pearson's correlation (r) analysis were utilized.
Results: Forty-one percent reported chronic pain. Survivors with chronic pain (n=343) experienced
significantly more fatigue (73% vs. 32%, p< .0001), depression (21% vs. 7%, p< .0001) and anxiety
(40% vs. 19%, p< .0001), than survivors without chronic pain (n=491). Correlations were found for r
pain-fatigue = .47, r pain-anxiety = .35, r pain-depression =.37, r fatigue - anxiety =.49, r fatigue-depression = .58, r anxiety-depression
= .68; all p < .0001. Sixteen percent of survivors with chronic pain also reported concurrently, fatigue,
anxiety and depression. In contrast 4% of survivors without chronic pain reported anxiety, depression
and fatigue.
Conclusion: Breast cancer survivors with chronic pain experience more fatigue, anxiety and
depression than those without. The findings support the existence of the symptom cluster of ”chronic
pain, fatigue, anxiety and depression”.
744
AN INTERNATIONAL ROAD MAP TO IMPROVE PAIN ASSESSMENT IN PEOPLE WITH
IMPAIRED COGNITION: THE DEVELOPMENT OF A TOOLKIT
W. Achterberg, EU-COST Action Pain in Impaired Cognition
Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands
Background and aims: In the last decades, it has become clear that the recognition of pain in people
with impaired cognition and communication problems is troublesome, because of their inability to self
report.
International epidemiological research shows that especially people with dementia suffer from
inadequate pain management in general.
Instruments have been developed that rely on observations of behaviors and facial expressions,
trying to find an alternative for self report. Systematic reviews on these instruments show that these
instruments often lack sufficient reliability, unclear face and construct validity, poor or untested
usability and clinical (international) implementation.
Methods: The EU-COST action “Pain in impaired cognition, especially dementia” that started in 2011
and consists at this moment of 14 European nations and Australia as an associated country) is a 4
year EU-initiative to combine knowledge of experimental and clinical researchers with the experience
of clinical experts. Its goals are to reduce the fragmentation in international research and to strive for
international cooperation, bringing together leading researchers from a wide range of scientific
disciplines. The major aim is the development of a comprehensive and internationally agreed-on
Meta-tool for older adults, targeting the various subtypes of dementia and cognitive impairment
disorders.
Results: We will present the first results of the selection of scales and items out of these scales that
represent the central signs of pain: facial activity, body movement and vocalization, and describe the
road-map to further psychometric development and testing.
Conclusions: International collaboration resulted in a promising toolkit for pain in dementia.
745
DOES AWARENESS OF OWN GENDER ROLE EXPECTATIONS OF PAIN AFFECT
EXPERIMENTALLY INDUCED PAIN RESPONSES?
1
2
2
O.A. Alabas , N. Rose , O. Tashani
1
2
Epidemiology and Biostatistics, University of Leeds, Leeds Metropolitan University, Leeds, UK
Background: Studies found that sex differences in response to pain were mediated by gender role
expectations of pain (GREP). However, it is not known whether the awareness of one's own gender
role expectations of pain affect pain responses? The aim of this study was to investigate whether
awareness of own GREP might affect cold pain responses.
Method: Twenty participants (10 female) underwent one cycle of cold pressor pain test (CPT) and
completed GREP. Participants were assigned into two groups (5 of each sex); Group A who
completed the GREP before the CPT becoming aware of their own gender role expectations of pain,
whereas group B completed the GREP after the CPT, thus they were not aware of their own gender
role expectation of pain during the pain test.
Results: Independent t-tests found no significant differences between GREP scores of the two
groups. However, group A who were aware of their gender role expectations of pain indicated higher
intensity ratings (mean (SD), 60.5 (12.7)) than group B who were not aware of their GREP scores
(mean (SD), 51.6(16.3)) p=0.05). There were no significant differences between the groups in pain
threshold, tolerance and unpleasantness.
Conclusion: Awareness of self gender role behaviour as measured by GREP has little effect on pain
threshold and pain tolerance scores in CPT but may affect pain intensity ratings resulting in slightly
higher scoring. On the other hand going through experimental pain induction session has little effect
on how people regard their gender role expectation of pain.
746
A SYSTEMATIC REVIEW OF STUDIES USING THE ADOLESCENT PEDIATRIC PAIN TOOL
1
1
1
1
A. Fernandes , C. Campos , L. Batalha , A. Perdigão , A. Oliveira
1
2
2
Health Sciences Research Unit, Nursing, Coimbra School of Nursing, Faculty of Psychology,
University of Coimbra, Coimbra, Portugal
Background: The Adolescent Pediatric Pain Tool (APPT) is a multidimensional self-report
assessment tool to assess pain location, intensity and quality in hospitalized children aged 8-17
years-old. To our knowledge, no systematic reviews have examined its use and clinical and research
utility.
Objectives: To identify ages, health conditions, settings, and purpose for which APPT has been
used; components of the APPT used; and clinical and research utility of the APPT.
Design: A systematic review of the literature was conducted searching CINHAL, Medline, PubMed,
Scielo and PsycInfo for primary studies that used the APPT. Assessment of full-texts for inclusion was
performed independently by two reviewers and so was their critical appraisal. Data extraction covered
sample characteristics, setting, purpose, study design, outcome measures and reports of clinical and
research utility.
Findings: Twenty-two primary studies were included. APPT has been used in patients 2-68 years-old
with acute and chronic conditions, in and out of hospital. All but two studies used the three
components of the APPT. The outcome measures most frequently used are total number of sites
marked by the patients, mean pain intensity and mean number of pain descriptors selected. Studies
defend its use in clinical practice since it provides a deeper understanding of the pain experience and
helps clinicians tailor pain control interventions. Research utility of the tool has been reported based
on its validity, reliability and sensitivity to pain control.
Conclusion: Findings support the use of the APPT in research and clinical practice to assess pain in
a multidimensional way.
747
METRIC EFFECTS OF TAKING TEARS OUT OF THE WONG-BAKER FACES PAIN SCALE
1,2
3
1,2
1,2
3
L. Batalha , A. Oliveira , A. Fernandes , J. Gonçalves , R. Viegas , N. Teixeira
1
2
3
3
Nursing School of Coimbra, Health Sciences Research Unit - Nursing, Institute of Cognitive
Psychology-University of Coimbra, Coimbra, Portugal
Background and aims: Whether or not to use anchoring elements such as smiles and tears in pain
faces scales remains an open issue (Tomlinson et al., 2010). A first step towards settling this issue is
to establish their effects over such features as the dynamic range of the scales and/or their equalinterval properties. This work is aimed at evaluating the effects of removing tears as an upper anchor
in the WBFPRS.
Methods: The methodology of information integration theory was used (Anderson, 1982). Two groups
of children aged 9-11 performed on a task requiring them to evaluate the overall pain conveyed by
pairs of faces arising from the factorial combination of the 6 WBFPRS faces with those (also 6)
constituting the FPS-R. Answers were given on a graphical rating scale anchored at “no pain” and “a
great lot of pain”. Tears were removed from the WBFPRS in one of the groups.
Results: Children integrated the two pain informers through an averaging model, which allowed
deriving functional scale values (interval level) and measures of relative importance (ratio level) for
each face.
Conclusions: The range of the WBFPRS without tears was reduced. The WBFPRS become slightly
closer to the equal interval ideal. All its faces were evaluated as more intense than in the tears-in
version, except for the last one. The relative importance of this face was sizably diminished.
References: Anderson, N. H (1982). Methods of information integration theory. NJ: Lawrence
Erlbaum.
Acknowledgements:
Foundation for C&T).
Work
supported
by
grant
PTDC/PSI-PCO/107910/2008
(Portuguese
748
EXPLORING THE ROLE OF PAIN IN PREDICTING PRESSURE ULCER DEVELOPMENT
1
2
3
4
5
2
2
6
M. Briggs , M. Collison , L. Wilson , E. McGinnis , C. Dealey , J. Brown , S. Coleman , N. Stubbs ,
2
7
2
R. Stevenson , E.A. Nelson , J. Nixon
1
2
Institute of Health and Wellbeing, Leeds Metropolitan University, Clinical Trials Research Unit,
3
4
University of Leeds, Mid Yorkshire NHS Trust, Tissue Viability Service, Leeds Teaching Hospitals
5
6
NHS Trust, Leeds, University of Birmingham, Birmingham, Leeds Community Healthcare Trust,
7
School of Healthcare, University of Leeds, Leeds, UK
Background and aims: Pain can aid diagnosis for many conditions. Patients with pressure ulcers
(PU) have reported pain before and after ulceration. However, it is not known whether pain can
predict ulceration. We sought to examine the predictive ability of pain for predicting pressure
ulceration.
Method: A prospective cohort study with 30 days follow-up, in 26 acute and community UK NHS
centres involving patients at high-risk of PU development.
Results: Of 3826 patients screened, 634 were recruited to the study of whom 32 were lost to followup (analysis population 602). A quarter (25%:152/602), developed a new PU. The risk of PU
development for people with pain at a skin site was 28% (130/464). 138 people had no pain at
baseline and of these only 15% (22/138) developed a new PU. Univariate logistic regression identified
3 baseline factors which were statistically significantly associated with the odds of developing a new
Category ≥ 2 PU: the presence of Category 1 PU (OR 3.20 CI 2.63 to 4.74, p< 0.0001), alterations to
intact skin (OR 1.79, CI 1.20 to 2.66, p=0.0045) and pain (OR 2.05, CI 1.25 to 3.38, p=0.0047).
Conclusions: These findings highlight the importance of assessing and responding to pain and the
role it plays in pressure ulcer prevention.
Acknowledgements: Research funded by the National Institute for Health Research (NIHR) under its
Programme Grants for Applied Research Programme (RP-PG-0407-10056). The views expressed are
those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
749
DO FIBROMYALGIA PATIENTS AND PATIENTS WITH CHRONIC FATIGUE SYNDROME
ESTIMATE THEIR SLEEP DIFFERENTLY FROM OTHER PATIENTS?
1
2
G. Brusselmans , H.N. Carvalho , A. Mariman
1
3
2
Pain Clinic, University Hospital Ghent, Ghent, Belgium, Universidade do Porto, Porto, Portugal,
University of Ghent, Ghent, Belgium
3
Background and aims: Up to 70% of fibromyalgia (FM) patients suffer from sleeping problems.
We investigated how accurate patients' rapportations were by comparing their estimations of sleeping
times with polysomnographic data. Are fibromyalgia and chronic fatigue syndrome (CFS) patients
more or less accurate in estimating their sleeping times compared to other patients with sleeping
problems ? These are questions that penetrate the field of interoception - the experience of bodily
processes.
Methods: Polysomnographic data from 925 patients with sleeping problems visiting the policlinic of
internal medicine were analysed. Patients were evaluated for FM and CFS and clustered in 4 groups:
1) FM only (76 patients)
2) CFS only (87 patients)
3) FM and CFS (92 patients)
4) None (609 patients)
2 sleep variables obtained objectively and subjectively were extracted:
1) Total Sleep Time (TST)
2) Time of Sleep Onset (TSO)
Statistical analysis was done by paired sample t-test within each group.
Results: Patients with Fibromyalgia appear to be better estimators than controls concerning SOTs.
This phenomenon is more pronounced when there is a co-diagnosis of CFS.
Concerning TSTs, CFS patients revealed to estimate it less accurately than controls, with their
estimates being approximately two-times less accurate.
Conclusions: In spite of our observations, one must note that the control group (no FM, no CFS)
consists of patients with general health complaints, and therefore, is not ideal.
When comparing our data with literature findings in healthy populations we observe that SOT and
TST estimations in healthy controls follow an opposite pattern.
750
ITALIAN CHRONIC PAIN WEBSITES: ASSESSMENT OF QUALITY INFORMATION USING THE
DRAGULANESCU INSTRUMENT
1,2
3
1
1
A. Camilloni , M.G. De Marinis , R. Latina , G. Tarsitani
1
2
Public Health and Infectious Diseases, Sapienza University of Rome, National Health Service, ASL
3
Roma D, Campus Biomedico, University Rome, Rome, Italy
Background and aims: The statistics demonstrate the negative impact of chronic-pain. Searching for
health information is one of the most common tasks performed by Internet users and nearly 70 % of
patients did so before visiting a doctor's office; 5% of all Internet searches are health related, with up
to 7 million conducted each day. However, Internet is often an unsafe, unstructured, uncontrollable
occupational hazard with strange customs and jargon. Several reports have questioned the accuracy
and readability of health related websites, however, none have investigated the quality of information
relating to Italians' website.
Methods: Five key terms (pain, chronic pain, back pain, arthritis, fibromyalgia) were entered in
Google, Virgilio, MSN, the most used Italian search engines. Websites were assessed using the
Dragulanescu-instrument as a quality index on the first fifteen links (Italian language). Grade level
readability ratings were assessed using the eight evaluation criteria of Dragulanescu scores:
accuracy, authority, coverage, currentness, density, interactivity, objectivity, promptness.
Results: 225 links were searched, less than 50% were assessed because there were duplicates:
often the included websites don't offered quality, readability and suitability health related patients'
information . Website that scored high, about 40%, contained good topics about pain conditions,
treatments and interactive options.
Conclusions: The overall quality of pain websites is moderate, with some shortcomings. An ideal
website may be impossible, but surely an attempt to satisfy basic user needs is feasible. The
Dragulanescu questionnaire could be used in order to propose some basic criteria to select chronicpain suitable websites.
751
AGREEMENT BEETWEEN VERBAL AND ELECTRONIC VERSIONS OF THE NUMERICAL
RATING SCALE (NRS-11) WHEN USED TO ASSESS PAIN INTENSITY IN ADOLESCENTS
E. Castarlenas, E. Sánchez-Rodríguez, J. Miró, R. de la Vega, R. Roset
Unit for the Study and Treatment of Pain - ALGOS, Research Center for Behavior Assessment
(CRAMC), Departament de Psicologia and Institut d'Investigació Sanitària Pere Virgili. Universitat
Rovira i Virgili, Tarragona, Spain
Background and aims: Electronic pain measures are becoming common tools to assess paediatric
pain intensity. The aims of this study were:
(1) to examine the agreement between the verbal and the electronic versions of the NRS-11 (vNRS11 and eNRS-11, respectively) when used to assess pain intensity in adolescents; and
(2) to report participants' preference between the two versions.
Methods: 191 schoolchildren enrolled in grades 7 to 11 (age mean=14.61; range=12-18) participated.
They were asked to report the highest intensity of the most bothersome pain using both the vNRS-11
and the eNRS-11. Agreement analyses were done using the Bland-Altman method, both at 80% and
95% confidence interval (CI). The maximum limit of agreement was set at ±1. Preference was also
requested.
Results: Limits of agreement at 80% CI: total sample (-0.61, 0.88); grade 7 (-0.63, 0.94); grade 8 (0.88, 1.16); grade 9 (-0.47, 0.75); grade 10 (-0.48, 0.87); grade 11 (-0.51, 0.58).
Limits of agreement at 95% CI: total sample (-1.01, 1.28); grade 7 (-1.05, 1.35); grade 8 (-1.42, 1.69);
grade 9 (-0.80, 1.08); grade 10 (-0.83, 1.22); grade 11 (-0.80, 0.88).
82.7% participants preferred the eNRS-11.
Conclusions: Pain intensity ratings on vNRS-11 and eNRS-11 seem to be comparable at 80% CI,
supporting that 95% CI may be a too strict criterion for agreement.
Acknowledgements: This study was partly funded by grants PSI2009-12193PSIC-MICINN,
Fundació La Marató-TV3 and by AGAUR(2009SGR 434). EC and ES-R work is supported by a
doctoral grant from the Catalan Government and CRAMC.
752
RELATION BETWEEN PAIN INTENSITY AND MEASUREMENTS WITH ALGOMETER AND
THERMOGRAPHY
D. Celan, M. Palfy, T. Rumpf, B. Jesensek - Papez
University Clinical Center Maribor, Maribor, Slovenia
Backgrounds and aims: Pain is often a disturbing symptom in numerous pathological conditions.
Pain intensity is evaluated with the VAS scale; however, we lack objective methods of measuring pain
intensity. In our study we tested the validity of measurements with algometer and thermography.
Methods: The upper part of the back and neck was symmetrically divided into 10 areas. 15 subjects
with a whiplash injury participated in the study. They provided an estimation of pain intensity for each
area using the VAS scale. We determine pain intensity in all areas with the algometer and measured
the average temperature with a thermographic camera.
Results: Measurements were performed on 150 areas. The calculation of Spearman correlation
coefficient between VAS results and algometry provided the value r = - 0.48 (p< 0.001) and between
VAS results and thermographic measurements r = 0.11 (p = 0.192).
Conclusions: The study has showed a moderate and statistically significant correlation between
algometric measurement and pain intensity evaluation with the VAS scale on the observed back area.
The results of the thermographic measurement were in negligible and statistically insignificant
correlation with the VAS evaluation.
Box plots: Boxplot 1: Box plot demonstrating the distribution of algometric measurements depending
on the VAS assessment.
753
QUALITY ASSESSMENT OF PAIN TREATMENT FACILITIES: A DELPHI STUDY
1
1
2
3
N. de Meij , J. Patijn , J. Maessen , T. van der Weijden , M. van Kleef
1
1
2
Anesthesiology and Pain Management, Maastricht University Medical Centre (MUMC), Patient Care,
3
Maastricht University Medical Centre, Department of General Practice/CAPHRI, School for Public
Health and Primary Care, Maastricht, The Netherlands
Background and aims: Since chronic pain may result in physical and psychological disabilities,
within the framework of the bio psychosocial model of pain, it is important to ensure that patients
receive the treatment that is most appropriate for their pain. Therefore, accessibility to an accurate
pain management facility is important. Access to appropriate services and treatments is the key to
achieving tangible improvements in pain management, in Europe. The aim of the study was to
develop expert agreed long-list quality indicators to provide the individual pain patient guarantees for
proper multidisciplinary diagnostics and treatment modalities.
Methods: In 2012, the University Pain Centre Maastricht of the department Anaesthesiology and Pain
Management of the Maastricht University Medical Centre conducted a Delphi study in collaboration
with the Board of the Pain Section of the Dutch Society of Anaesthesiologists (NVA). Three rounds
were established with experts from the field: a face-to-face meeting, a web-based questionnaire, and
a telephone conference.
Results: An expert agreed long-list with 22 quality indicators appropriate for registration quality and
certification of a Pain Clinic and Pain Centre.
[Quality indicators]
Conclusions: This result may contribute and improve the quality of pain practice management.
Registration quality provides organizational insight and transparency for patients, pain specialists, and
other health care professionals. Certification of pain treatment facilities can be a compulsory
motivation to improve the quality of pain practice management in Europe.
754
MEASUREMENT OF PAIN IN DEMENTIA: THE CONTENT VALIDITY OF NEW TOOLKIT ITEMS
M.W.M. de Waal, S.A. van Vuuren, W.P. Achterberg
Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands
Aim: Pain-assessment in dementia patients is challenging, because of diminished self-report. In
developing a new European toolkit for measurement of pain in dementia patients, items have been
selected by a European working group from existing instruments, which were thought to be promising.
We aim to study content validity, and to study whether all items are indicative for pain, or that potential
users interpret them to be more related to depression, delirium, dementia, or anxiety disorder.
Methods: Interviews were held with 15 Dutch experts in the field, whose opinion was asked whether
occurrence of items is an indication of pain, about relevance and comprehensiveness of the list of 35
items, and whether items fit most with pain or another disorder. Meanwhile items have been
translated following international guidelines.
Results: Over 70% of the items were indicated as probably or definitely indicative for pain by more
than half of the interviewed persons. Indicated relevance and clarity of items varied. Several
additional items were suggested, e.g. not using a body part. About one third of items were interpreted
by more than 50% of interviewed persons to be specific for pain, e.g. tightened lips and groaning.
Another third was indicated to be more related to other disorders, e.g. disinterested to depression and
offensive wording to dementia itself.
Conclusions: This study gives material for revision of the list of items, with use of indicated relevance
and suggested items.
755
SCREENING FOR PRESENCE OF PAIN AND NEED FOR CARE AT OLD AGE IN GENERAL
PRACTICE
M.W.M. de Waal, W.P.J. den Elzen, W.P. Achterberg, J. Gussekloo, J.W. Blom
Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands
Background: Screening can be a valuable aid to realize pro-active care for older persons with pain.
The Pain intensity, Enjoyment in life, General activity questionnaire (PEG) is developed as an ultrabrief screener in primary care, but not tested in older persons.
Aim: To test the PEG and a question on need for care as postal pain screener in older persons.
Methods: We sent screening questionnaires to 321 registered persons aged ≥75 years from 3
general practices. Screening included the three-item PEG and one question on need for care. A
sample of 95 participants was interviewed to assess pain (Brief Pain Inventory (BPI)), actual pain
treatment and need for care. Total PEG and BPI-scores were calculated as mean of all items (range
0-10).
Results: Of 243 participants to screening (response 76%), 68% reported pain. Median PEG-score
was 2.0 (IQR 0-4.7). In total 79 older persons (35%) had PEG-score≥4 points of whom 56% reported
current pain treatment and 15% need for care. Sensitivity for PEG-score < 4/≥4 was 0.81 and
specificity 0.78 to find scores ≥4 on one or both BPI-subscales during interview. The reply to need for
care was incongruent between screening and interview. Of interviewed participants with PEG-score
≥4 60% received treatment. Out of 17 without current pain treatment 10 reported pain, of whom 3
might have plans to ask help from a GP.
Conclusion: PEG can be used as postal screener for detecting presence of pain in older persons.
However, establishing need for (extra) care needs further elaboration.
756
CAPSAICIN (8%) PATCH INCREASES MULTIPLE ELECTRICAL NOCICEPTIVE PERCEPTION
THRESHOLDS IN HEALTHY HUMAN SUBJECTS
1
1
2
2
2
R.J. Doll , J.R. Buitenweg , G. van Amerongen , J.L. Hay , G.J. Groeneveld , P.H. Veltink
1
1
Biomedical Signals and Systems, MIRA Institute for Biomedical Technology and Technical Medicine,
2
University of Twente, Enschede, Centre for Human Drug Research, Leiden, The Netherlands
Background: Pre-operative nociceptive thresholds are able to predict patients susceptible to
developing post-operative chronic pain. Thresholds are dependent on stimulus properties (i.e. pulsewidth (PW), number of pulses (NoP), and inter-pulse interval (IPI)) and are related to different
mechanisms in the nociceptive system. Measuring multiple thresholds enables a detailed observation
of peripheral and central nociceptive processing. In this study, a model of capsaicin
defunctionalization was used to investigate the effect on multiple simultaneously measured electrical
nociceptive perception thresholds.
Methods: A cutaneous capsaicin patch (8%) was applied to the upper leg in 8 healthy human
subjects. Perception thresholds (four sets of stimulus parameters varying PW, NoP, and IPI) were
measured using a 5-needle electrode. Thresholds were measured on both the treated and adjacent
untreated sites prior to application of the patch (day 0), and on subsequent days 2, 7, 28, and 84.
Results: Preliminary results showed that thresholds depended on stimulus parameters. Moreover, an
increase in threshold on capsaicin treated sites was observed in three settings for days 7 and 28
compared to untreated sites.
Conclusions: With the presented data, increased electrical perception thresholds were observed due
to capsaicin. Furthermore, this study confirms that thresholds depend on stimulus parameters. These
data can be used to build a mathematical model of the nociceptive system and be used to interpret
nociceptive changes.
Acknowledgements: This research is supported by the Dutch Technology Foundation STW, part of
the Netherlands Organisation for Scientific Research (NWO) and partly funded by the Ministry of
Economic Affairs, Agriculture, and Innovation.
757
RESEARCH ON PAIN AWARENESS OF STUDENTS WHO UNDERGO HEALTH EDUCATION
C. Algun, F. Mutluay, G. Ertunc
Physiotherapy and Rehabilitation, Istanbul Medipol University, Istanbul, Turkey
Objective: To search pain awareness of students who undergo health education, the effects of pain
on their lives and treatment attempts.
Methods: Pain Evaluation Scale has been implemented on students who study Health Sciences in
Medipol University, to question body diagram and level of pain along daily and social activities via
VAS scale.
Results: 230 students (Female/Male:156/74) were involved in our study.
The percentage of pains was distributed on vertebrael problems in the rate of 46,32%, lower limb in
25,97%, upper limb in 21,21% and head pain in 20,35%.
47 students had seen a doctor because of their pain. 15 had orthopaedic, 5 had neurological and soft
tissue-related and 4 had infectional problems detected. 19 of them received only medications, 5 only
exercises, 17 medications and exercises whereas 6 received no treatment.
A positive correlation between frequence of doctor-visiting and pain level, frequence of doctor-visiting
and number of pain foci was established.
Pain had effects on general mobility, psycology, gait capacity, ADL and work, social relations, sleep
and joy in the aligned rates of 74,47%, 77,13%, 62,77%, 70,75%, 59,57%, 69,68% and 72,34%.
Conclusion: The increase of pain foci may induce the severity of these effects.
The reasons of pain increase in youngsters may be indicated as computer-use, wrong posture arising
from video games, over training or overuse and sedentary life. Students should be educated on pain
awareness, managing methods and correct posture, so that cumulative traumas may be avoided.
758
ASSESSMENT OF QUALITY OF LIFE IN CHRONIC PAIN PATIENTS AND COMPARISON WITH
HOSPITAL WORKERS
L. Wilson, V. Gadiyar
Pennine Acute Hospitals NHS Trust, Manchester, UK
Background and aim: Chronic pain patients have problems with their daily activities, relationships
and employment in addition to physical health. Due to this, chronic pain is often linked with an overall
1
poorer quality of life (QOL). This study examined the QOL of patients attending chronic pain clinic in
comparison to hospital workers
Methods: The RAND 36 item health survey was used which divides quality of life into 8 different
aspects (physical functioning, emotional functioning, social functioning, energy/fatigue, pain, general
health perceptions, limitations due to physical health, and limitations due to emotional health). 60
Patients and 21 workers participated. Each person had percentage score calculated for each of 8
aspects of QOL (100 being a better score than 0).
Results: The results showed that in all 8 areas of QOL, the clinic attendees had a lower mean score
than the workers. In most cases the mean scores of the clinic workers were approximately double
those of the clinic attendees with the exception of 2 areas where there was a considerably larger
difference: ' limitations due to physical health' (attendees mean = 17.67, workers mean = 71.43) and
'pain' (attendees mean = 27.67, workers mean = 82.87).
Conclusion: Patients have lower QOL compared to workers. Largest disparity was found in
'limitations due to physical health' and 'pain'. A multi-disciplinary team approach could be step forward
in improving these patients overall QOL.
Elliott TE, Renier CM, Palcher JA. Chronic pain, depression, and quality of life: correlations and
predictive value of the SF-36. Pain Med. 2003 Dec;4(4):331-9.
759
KNOWLEDGE AND ATTITUDES OF NURSES RELATED TO MANAGEMENT OF PAIN IN
MEDICAL AND SURGICAL WARDS OF A TERTIARY HOSPITAL
1,2
2,3
3
3
C. Gueniat , F. Teike Lüthi , F. Nicolas , P. Thomas , A.-S. Ramelet
1
1,2
2
Haute Ecole de Santé Vaud (HESAV), University of Applied Sciences, Western Switzerland, Institut
3
Universitaire de Formation et de Recherche en Soins (IUFRS), University of Lausanne, Centre
Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
Background and aims: Pain management in inpatients is not optimal. Unrelieved pain can result in
physiological and psychological complications with economic implications. Multiple factors can
contribute to inappropriate pain management, nurses' attitudes and knowledge being one of
them.This descriptive study aimed to identify the pain management knowledge and attitudes of nurses
working in surgical and medical wards of a tertiary hospital in Western Switzerland.
Methods: Following standard translation and ethics approval, the Pain knowledge and attitudes
(PAK) questionnaire was sent electronically to all nurses working on a permanent contract for more
than 3 months in four medical and surgical wards of the tertiary hospital. Reminders were sent
automatically to non-respondents 2 and 4 weeks after the first email out. The PAK includes 10
questions rated on a 5-point Likert-type scale, ranging from 0 “strongly agree” to 4 “strongly disagree”.
For the analyses, the data have been dichotomised into “correct” and “wrong” answer.
Results: Seventy consenting nurses returned their completed questionnaire (65.4% response rate).
The percentage of correct answers was 68.7. Questions that were rated the lowest were related to
beliefs about opiates´ side effects (30%), patient pain self-assessment (55.7%) and proxy pain
(48.6%).
Conclusions: These results show a proportion of knowledge below the expected standard of 80%.
They are not different to other investigations on the same subject in Western countries, reflecting
nurses' attitudes about not recognising patient's pain self-assessment being the most reliable
indicator, and gaps in knowledge related to opiates and pharmacology.
Mundipharma supported part of this study.
760
BODY PERCEPTION AND MOTOR PLANNING AFTER LIMB FRACTURE
1
2
2
3
3
2
4
3
J. Hall , S. Nelson , J. Bailey , J. Rowett-Harris , P. Tarassoli , S. Palmer , A. Goebel , R. Atkins , C.
2,5
McCabe
1
2
Bath Centre for Pain Services, Royal National Hospital for Rheumatic Diseases, Bath, University of
3
4
5
West of England, Bristol Royal Infirmary, Bristol, University of Liverpool, Liverpool, Royal National
Hospital for Rheumatic Diseases, Bath, UK
Background and aims: Wrist and ankle fractures are common injuries worldwide. Mkandawire
(2002) reports that < 60% of limb fracture patients experience long-term disability and chronic pain.
Chronic pain is associated with sensorimotor dysfunction and yet little is known about the impact of
fractures on this system. For example what is the effect of fracture on body schema and motor
planning? The aim of this pilot was to establish the nature and prevalence of sensorimotor function
and body perception in the affected limb of patients with limb fractures.
Methods: Patients with unilateral unstable ankle or wrist fracture completed tests of sensorimotor
function at approximately 6 weeks (Time 1) and 6 months (Time 2) after injury. Body Perception
Disturbances (BPD) and Imagined Movements (IM) were collected at T1 only. Self-report
questionnaires captured function, mood and quality of life (T1 and 2).
Results: 53 patients, mean age 54.2 (SD:17.7), 17 males, wrist fracture=36, ankle= 17) participated.
IM were significantly more difficult to perform with the affected than unaffected limb (p=0.01) with 36%
experiencing reduced vividness. 62% reported BPD of the affected limb with 5.6% reporting the loss
of a segment of the affected limb. Significant negative correlation was noted between IM and patient
reported recovery at T2.
Conclusions: This pilot demonstrated that disruption to motor planning and BPD are common postfracture. Further study is needed to replicate these results and examine whether novel treatment
strategies to reverse this dysfunction reduces the long-term fracture burden.
761
THE EFFECTS OF HYPERVENTILATION ON BISPECTRAL INDEX UNDER NITROUS OXIDESEVOFLURANE ANESTHESIA
1
1
2
2
1
1
Y. Horikoshi , T. Nakamura , Y. Yamanishi , K. Onuki , Y. Iwase , H. Nagasaka , N. Matsumoto
1
1
2
Anesthesiology, Saitama Medical University, Moroyama-Machi, Anesthesiology, Meikai University,
Sakado, Japan
Background: It is appreciated that hyperventilation increases analgesic effects of nitrous oxide (N 2O)
anesthesia. However, it is not clear whether hyperventilation changes bispectral index (BIS) values
under general anesthesia.
Methods: Thirty six surgical patients were enrolled in this randomized study. After induction the lungs
were ventilated mechanically with maintained with N2O (4l/min）-oxygen (2l/min）-sevoflurane (1%)
anesthesia. Tidal volume was 10 ml/kg and respiratory rate was 8 breaths/min until 15 min after
intubation. In normocapnia group mechanical ventilation was kept the same condition until 30min after
the intubation. In hypocapnia group hyperventilation was induced by tidal volume of 10ml/kg and
respiratory rate of 14 breaths/min from 15 min up to 30min after the intubation. 95% spectral edge
frequency (SEF95), amplitude of EEG (AMP), and BIS values were measured every 5 min after
intubation until 30min. Fifteen min after the intubation, the data was recorded as a baseline values.
Result: BIS values in the hypocapnia group were significantly lower from 5 to 15 min than those in the
normocapnia group. In hypocapnia group BIS and SEF95 decreased and AMP, but not significant,
increased with hyperventilation compared to those in normocapnia group.
Conclusion: Although it is reported that hyperventilation-induced hypocapnia at a level of 25 mmHg
in PaCO2 does not influence the BIS values under propofol anesthesia, our present results showed
that hyperventilation with hypocapnia to a PaCO2 of about 28.5mmHg induced a decrease in BIS and
SEF95 from 5 or 10 min after the start of hyperventilation without MAP and HR changes.
762
COMMUNICATION OF ACUTE POSTOPERATIVE PAIN (CAPP STUDY) - PHASE 1: PATIENTS'
DESCRIPTION OF THE DIMENSIONS OF PAIN AFTER KNEE REPLACEMENT
1
1
2
S.E. Hunter , M. Botti , T. Bucknall , L. Rhodes
1
3
2
Epworth/Deakin Centre for Clinical Nursing Research, Deakin University, Melbourne, Alfred Health,
School of Nursing and Midwifery, Deakin University, Burwood, VIC, Australia
3
Background and aims: Severity of postoperative pain is commonly evaluated using an 11-point
numerical rating scale (NRS), but application of the scale is associated with ambiguity and
ambivalence for both patients and clinicians as patients attempt to identify a number that represents
their pain experience. The overall aim of this sequential, multiphasic, mixed methods study is to refine
patient reporting of pain intensity using the NRS. In Phase 1 characteristics of the dimensions patients
use to attribute a particular numerical rating to postoperative pain intensity were investigated.
Methods: An exploratory, descriptive design of a stratified (age, sex and pain intensity) sample of 40
patients (Male=20, Age< />65 = 20; Female=20, Age < />65 =20), 24 hours after orthopaedic surgery
was used. Semi structured interviews incorporating open ended questions and validated pain
measurement tools explored and generated factors associated with the assignment of a numerical
rating to pain intensity.
Results: Emerging themes for determining pain intensity support a priori factors considered by
patients that include: pain interference with function; quality of the pain; urgency for treatment and
perceived personal tolerance for pain. Patients use the scale end points and previous experience of
pain as a guide for locating their current pain on the scale.
Conclusions: Elaboration of the common factors patients use to arrive at a pain rating will inform the
development of a standardised approach to the clinical application of the NRS in the postoperative
orthopaedic context.
Susan Hunter received an Australian National Health & Medical Research Council postgraduate
scholarship.
763
THE STRUCTURE OF POST-OPERATIVE PAIN EXPERIENCE: A CROSS-CULTURAL
EXAMINATION OF THE REVISED AMERICAN PAIN SOCIETY PATIENT OUTCOME
QUESTIONNAIRE (APS-POQ-R)
1
1
2,3
4
D. Khaw , M. Botti , E.B. Joergensen , B. Rasmussen , S. Hunter
4
1
Epworth/Deakin Centre for Clinical Nursing Research, Deakin University, Melbourne, VIC, Australia,
3
Department of Nursing Research, VIA University College, Holstebro, Hospitalsenheden Vest,
4
Region Midtjylland, Denmark, School of Nursing and Midwifery, Deakin University, Melbourne, VIC,
Australia
2
Background and aims: Culturally appropriate and validated pain assessment instruments are
required to optimise the management of patient pain. The Revised American Pain Society Patient
Outcome Questionnaire (APS-POQ-R) is a widely employed instrument with established construct
validity among North American (Gordon et al., 2010) and Icelandic (Zoëga, Ward, & Gunnarsdottir,
2012) adult inpatients. To-date however, the latent structure and cross-cultural factor stability of this
instrument has not been examined. This study aimed to explore the factor structure of the APS-POQR among Danish and Australian medical-surgical patients via exploratory factor analysis (EFA).
Methods: Study data were two point prevalence pain surveys. Danish participants (n=268) were adult
orthopaedic (23.5%), gynaecological (14.9%), urological (19.4%) and gastrointestinal (42.2%) surgical
patients. Australian data were 408 pain measurements of 257 unique adult orthopaedic surgical
patients and 151 repeated measures. We conducted EFA via principal axis factoring with direct
oblimin (oblique) rotation.
Results: Horn's (1965) parallel analysis indicated that Australian and Danish factor solutions
consisted of three and four factors respectively. There was minimal variation in the pain measurement
factors between solutions. These were factors of pain magnitude and factors concerning adverse
psychological and physical outcomes. The Australian solution however, included a perception of care
factor not extracted by the Danish solution.
Conclusions: EFA provided support for the construct validity of the APS-POQ-R among Danish and
Australian medical-surgical patients. Results indicated cross-cultural stability of the pain measurement
factors but suggested however, that the perceptions of care factor may not be stable across varied
cultural or treatment contexts.
764
RELIABILITY AND COMPARABILITY OF PAPER AND COMPUTER QUESTIONNAIRES IN THE
FINNISH VERSION OF THE TAMPA SCALE OF KINESIOPHOBIA
1
1
2
1
P. Koho , S. Aho , H. Kautiainen , T. Pohjolainen , H. Hurri
1
1
2
ORTON Rehabilitation Centre, Helsinki, Unit of Family Practice, Central Finland Central Hospital,
Jyväskylä, Finland
Objectives: The aim of this study was to estimate the test-retest reliability and comparability of paper
and computer versions of the Finnish version of the Tampa Scale of kinesiophobia among chronic
pain patients.
Participants: The sample comprised 94 patients with chronic musculoskeletal pain participating in a
pain management or individual rehabilitation program. The group rehabilitation design consisted of
physical and functional exercises, an evaluation of the social situation, a psychological assessment of
pain-related stress factors, and personal pain management training in order to regain overall
functioning and mitigate the inconvenience of pain and fear- avoidance behaviour.
Results: The mean (SD) TSK-FIN score for the computer version was 37.1 (8.1) [95% CI 35.5 to
38.8], whereas for the paper version it was 35.3 (7.9) [95% CI 33.7 to 36.9]. The mean difference
between the computer and paper version was 1.9 [95% CI 0.8 to 2.9]. The test-retest repeatability for
the paper version was 0.89, and 0.88 for the computer version. The internal consistency was
considered to be good for both versions of the TSK-FIN. The ICC for comparability was 0.77 [95% CI
0.66 to 0.85], indicating substantial reliability between different methods.
Conclusion: Both versions of the TSK-FIN demonstrated substantial inter-test reliability, good testretest reliability, internal consistency and limits of agreement, suggesting their suitability for clinical
use. However, there was tendency that subjects scored higher when using computer version. That is
why in ideal situation the data should be collected in similar manner in each phase of rehabilitation or
clinical research.
765
DEVELOPMENT OF A STANDARDISED METHODOLOGICAL APPROACH TO PROMOTE AND
EVALUATE INTERVENTION INTEGRITY IN COMPLEX BEHAVIOUR CHANGE INTERVENTIONS
FOR PAIN
1
1
1
2
2
T. Mars , D. Carnes , K. Homer , D. Ellard , M. Underwood , S.J. Taylor
1
1
2
Queen Mary University of London, London, Warwick Medical School, Coventry, UK
Background and aims: There has been a growth in complex interventions focussed on changing
individual behaviour especially for pain management. The evaluation of complex interventions is
under-developed and fidelity assessment is essential to test the reliability and validity of complex
interventions commonly used in pain management. We aimed to develop and test evaluation tools
designed to assess the integrity of the delivery of a self-management course for chronic pain and
make recommendations to improve the assessment of adherence and competence in delivering
complex interventions.
Methods: We evaluated a self-management course. Courses were audio recorded. A session specific
adherence evaluation form was constructed based on the content of the course manual. A generic
competence evaluation form using criteria based on a consensus of what constituted good course
facilitation was designed. Researchers listened to and reviewed a randomly selected sample of
behaviour change sessions from each course.
Results: The evaluation forms were reliable and had good face validity. The intervention was
delivered with high levels of adherence, however assessed facilitator competence exhibited more
variability. The assessment of competence proved to be challenging and presented a high coder
burden.
Conclusions: The scientific benefits of monitoring and assessing adherence and competence at the
point of course delivery can be realised by embedding the principles of fidelity measurement within
the design of courses and the training and assessment of those delivering the intervention. More work
is necessary to ensure that more robust systems of fidelity evaluation accompany the growth of
complex interventions.
766
PAIN AS THE FIFTH VITAL SIGN IN GALICIA: OVERCOME CHALLENGE
M.-D. Martín-Rodríguez, M. Carreras-Viñas, B. García-Cepeda, B. Fiuza-Barreiro, B. RodríguezPérez, B. Pais-Iglesias, M.-I. Graña-Garrido
Quality Management, Galician Health Service, Santiago de Compostela, Spain
In 2010, the Galician Health Service (SERGAS) set forth the “Integral Pain Care Strategy” within the
Strategy “SERGAS 2014: public healthcare at the patient's service”.
In 2011 pain evaluation as a fifth vital sign is implemented in all 15 hospitals belonging to the Galician
Health Service, including the Visual Analogue Pain Scale in the vital signs chart within the
Management of Care Application (GACELA) data record. The following standard was included as an
objective in the management contract which is signed by all hospital directors: that 50% of all inpatients have a pain evaluation register in their vital signs chart.
Results: In 2011 pain was registered as a fifth vital sign in 71 235 in-patients (32.3%). In 2012 was
registered in 152997 in-patients (69,8%). Of all in-patients who had a pain register, 46,3% suffered
pain with VAS value > 0. Of these, 58,1% were female (39.4% age > 60) and 41,9% were male
(55.1% age > 60).
32,4% of patients, pain was due to a health illness, 23,3% due to surgery and 13,8% due to
traumatisms. 79.1% of patients had localized pain where the abdomen was the main localization
39.8%. The most frequent associated symptoms were nauseas/vomiting 5,4%.Pain ceased with
analgesia in 42.7% of patients and diminished in 34,12%. 2,1% required rescue analgesia.
Conclusions: Nearly half of all in-patients suffer pain, more so in females over 60 years old. The pain
evaluation procedure has allowed us to become aware of the real situation and to improve health-care
procedures.
767
CULTURAL ADAPTATION AND REPRODUCIBILITY VALIDATION OF THE BRAZILIAN
PORTUGUESE VERSION OF THE SCALE PAIN ASSESSMENT IN ADVANCED DEMENTIA
(PAINAD-B)
1
1
2
M. Morete , A.C. Biagioni , F. Minson , C. La Selva
1
1
2
Hospital Albert Einstein, Centro Integrado de Tratamento da Dor, Sao Paulo, Brazil
Objective: To perform a semantic and cultural adaptation to Brazilian Portuguese of the PAINAD pain
scale; to evaluate its psychometric properties (validity, viability, inter-rater agreement, and clinical
usefulness).
Methods: The sample comprised 63 inpatients with neurological deficits, who were incapable of
making a self-report of their pain at a private hospital in Sao Paulo, Brazil.
Results: Among the 63 patients that participated in the study, 40 (63.5%) were female, median age of
87 years. Gleaned from the analysis of the principal components was the presence of a factor with a
value in itself of more than 1 (its own value = 2.254) with an explained variance of 45.07%.
Vocalization was the indicator on the scale with the greatest correlation with the factor (0.626), and
breathing was the one with the least correlation (0.077). Kaiser-Meyer-Olkin test (KMO) was used to
assess the adjustment of the factorial analysis, showing a value of 0.712. The scale showed
acceptable internal consistency. The body language indicator had the best correlation with the total
value of the scale (0.508), and the one that most contributed towards internal consistency of the scale
(0.503). The correlation verified among the nurses was 0.770, with a 95% confidence interval of 0.652
to 0.853.
Conclusion: The Brazilian version of the PANAID scale reveals in its factorial structure a factor that
explains almost half of the pain variance. A similar result was found with the original scale.
768
INVESTIGATION OF MUSCULOSKELETAL SYMPTOMS AMONG MANUAL LOAD HANDLERS:
QUESTIONNAIRE VERSUS PHYSICAL EXAMINATION
1
1
1
2
A.B. Oliveira , H.C. Nogueira , F. Locks , L. Carnaz
1
2
Departamento de Fisioterapia, UFSCar, Sao Carlos, Departamento de Fisioterapia, Universidade
Sagrado Coracao, Bauru, Brazil
Background and aims: Considering that workers performing heavy tasks also present work-related
musculoskeletal disorders in upper limbs, and the fact that standardized physical examination (SPE)
has been investigated only on subjects who perform repetitive tasks, the aim of this study was to
compare scores from the Nordic Musculoskeletal Questionnaire (NMQ) with findings and diagnosis
obtained from a SPE among manual load handles.
Methods: Seventy-eight male from an aircraft maintenance company participated in this study.
Musculoskeletal disorders and complaints were investigated by the NMQ and the SPE (Department of
Occupational and Environment Medicine of Lund University).
Results: Table 1 presents the number of workers reporting complaints, and presenting findings and
diagnosis in SPE; sensitivity and specificity of NMQ in detecting disorders diagnosed by SPE.
Region
Clinical
examination
Questionnai
re
Diagnosi Finding
s
s
Diagnosis
Findings
Sensitivit Specificit Sensitivit Specificit
y (%)
y (%)
y (%)
y (%)
Neck/Shoulders/Elbows/Ha
nds
20
72
20
45
81
26
83
Neck/Shoulders
19
69
16
37
85
22
89
Neck
16
60
13
31
87
19
90
Shoulders
13
55
7
31
95
13
100
Elbows/Hands
8
53
5
25
97
9
100
Elbows
0
22
0
100
100
0
100
Hands
8
52
5
25
96
10
100
[Table 1]
Conclusions: The comparison between scores from NMQ and SPE have shown different behavior
than the one observed in repetitive workers. It seems that load handlers have higher reporting rate
than diagnosis. Larger samples should be investigated.
769
CLASSIFICATION OF AND RISK FACTORS FOR AROMATASE INHIBITOR PAIN SYNDROMES:
A PROSPECTIVE MULTICENTER COHORT STUDY
1
2
3
4
4
5
F. Laroche , T. Medkour , J. Coste , P.H. Cottu , J.-Y. Pierga , D. Bouhassira , S. Perrot
1
2
6
3
Pain Center, Pierre et Marie Curie University, Internal Medicine and Pain Center, Biostatistics,
4
5
Paris Descartes University, Medical Oncology, Institut Curie, Paris, INSERM U 987, Ambroise Paré
6
Hospital, Boulogne, Internal Medicine and Pain Center, INSERM U 987, Hotel Dieu Hospital, Paris
Descartes University, Paris, France
Purpose: In this prospective multicenter study, we classified aromatase inhibitor (AI)-related pain
syndromes, assessed impact on daily life and identified their predictors, for the development of more
targeted prevention approaches.
Patients and methods: A one-year multicenter cohort prospective study, with six consultations with
pain specialists and rheumatologists, was carried out in women with early-stage breast cancer and no
pain beginning AI treatment. At initial assessment, we investigated potential clinical (demographic and
psychosocial, cancer characteristics and treatment, pain, sleep, rheumatology examinations, quality of
life), biological (sex hormones, vitamin D, bone biomarkers, oxidative stress, immunological and
inflammatory markers), environmental and genetic (polymorphism for pain mechanisms) risk factors
for pain.
Results: We evaluated a cohort of 135 women for one year: 77 developed pain, leading to AI
discontinuation in 12 cases. Five pain syndromes were identified: joint pain (36%), diffuse pain (22%),
tendinitis (22%), neuropathic pain (9%) and mixed pain (11%), most persisting (57%), with diffuse and
joint pains the most intense.
Risk factors for developing pain included higher levels of anxiety and impaired quality of life at the
initial assessment, whereas cancer characteristics, genetic background, inflammation, immunological
and hormonal status at baseline were not significant predictors.
Conclusion: For women without pain at start, there is a 57% risk of developing pain within the first
year of AI treatment. Assessment should focus on five pain syndromes, to optimize analgesic
management. Psychosocial factors are the principal risk factors for the development of AI-related
pain.
770
CONFRONTING PAIN EXPERIENCE IN DEPRESSED AND NOT DEPRESSED PATIENTS WITH
CRONIC AND PERSISTENT PAIN: USEFULNESS IN CLINICAL PRACTICE
1
2
1
1
1
1
1
L. Ravaioli , S. Bianconcini , G. Gallo , M. La Grua , V. Paci , G. Sindaco , M. Zanella , G. Pari
1
1
Medicina del Dolore - Multidisciplinary Pain Center, (Villa Serena, Private Hospital Forlì, S. Maria
2
Maddalena Private Hospital, Occhiobello, Centro Oncologico Fiorentino, Firenze), Forli, Department
of Statistical Sciences, University of Bologna, Bologna, Italy
Background and aims: Chronic and persistent pain are strongly correlated to Mood Disorders, often
of the Depressive Spectrum (McWilliams, “Mood and anxiety disorders associated with chronic pain”
Pain, 2003). The aim of this work is to observe any difference between the pain experience of
depressed patients and not depressed patients that referred to the Multidisciplinary Pain Center, and
if the Italian Pain Questionnaire can be useful to discriminate between this two groups.
Methods: The Italian Pain Questionnaire (QUID) (De Benedittis et al.“The Italian Pain Questionnaire”
Pain, 1988) is a multidimensional pain assessment tool preserving a close structural parallel to McGill
Pain Questionnaire. We have administered the questionnaire to 22 patients: 10 of them with a
diagnosis of Major Depressive Disorder (Depressed patients) and 12 patients not depressed. We
performed a statistical analysis in order to evaluate the presence of differences between the two
groups (T-test and F-test (Fisher).
Results: We have found that all the main classes of QUID (sensory, affective, evaluative and the
miscellaneous class) the NWC and the PRIrT are significantly higher (in mean) in the Depressed
Patients, whereas the Pain intensity does not affect significantly the two groups of patients in a
different way.
Conclusions: Pain experience is significantly different in the two groups of Depressed and Not
Depressed patients, regardless to the pain intensity, and it can be shown also by the QUID results.
QUID can be also useful in clinical practice as a first screening for patients.
771
ASSESSMENT OF THE AWARENESS OF BRAZILIAN ANESTHESIOLOGISTS OF THE
POSTOPERATIVE PAIN TREATMENT
1
1
1
2
3
1
F.S. Lopes , V. Romero , A.C. Duarte , P. Gusman , D.D.O. Silva , E.M. Ganem , G.A.M. Barros
1
1
Anesthesiology, Botucatu Medical School - UNESP - Univ. Estadual Paulista, Botucatu,
3
Anesthesiology, Meridional Hospital, Vitória, Innovation and Development, Anestech, Florianópolis,
Brazil
2
Background: There are no Brazilian data of the incidence of postoperative pain (PP), the most
incident type of acute pain.
Aims: This study aims to assess the awareness of the anesthesiologist on the PP and its treatment.
Methods: After approval by the Ethics Committee 500 anesthesiologists located in different regions of
Brazil were invited to answer the survey, available on the SurveyMonkey website, concerning specific
knowledge of PP and its treatment.
Results: For 71% of the 146 participants, amputation surgeries were pointed as the greatest risk of
chronic PP, according to literature. The majority (95%) responded that the PP is well managed in the
organizations they work for. In their opinion, the main concern of the patient prior to surgery is to
experience pain during the procedure, and secondly the fear of postoperative pain, what is discordant
with literature. In the same way, only 15% of them were able to recognize prolonged ileus as a
challenge in the postoperative period. The participants correctly pointed, as important factors for the
choice of analgesics and techniques employed, the physical status, surgery duration and topography.
For the responders, the use of analgesic medication "if necessary" should be avoided in PP (80%).
Conclusions: Due to little contact with the patients in the wards, Brazilian anesthesiologists are
possibly unaware of the real incidence of PP.
Acknowledgement: The authors would like to thank FAPESP for supporting this work.
772
IMPACT OF FULRANUMAB TREATMENT IN IMPROVING PHYSICAL FUNCTION, AFTER
CONTROLLING FOR PAIN INTENSITY, IN PATIENTS WITH CHRONIC OSTEOARTHRITIS PAIN
1
2
1
3
M. Rothman , K.F. Ho , S. Fleming , K.M. Kelly
1
2
3
Janssen Global Services, LLC, Washington, GA, USA, Stat-Tu Inc., Toronto, ON, Canada, Janssen
Research & Development, LLC, Titusville, NJ, USA
Background and aims: In an exploratory analysis, fulranumab (an investigational anti-nerve growth
factor drug) was examined for an independent effect on patient function versus improvement in
function as a consequence of pain relief alone.
Methods: The direct and indirect treatment effects of fulranumab (3mg dose) versus placebo on
physical function scales (Western Ontario and McMaster Universities Arthritis Index [WOMAC]
physical function, Brief Pain Inventory [BPI] interference and Short Form [SF]-36 physical function)
were assessed using a mediation analysis performed on data from a fulranumab phase-2 study.
Indirect effect was measured by improvements in pain intensity on numerical rating scale. Changes
from baseline to week-12 in pain intensity and function scales were evaluated to assess whether level
of pain relief was associated with improvement in function. Sensitivity analysis was performed.
Results: At week-12, fulranumab treatment resulted in significant improvements in pain intensity
(nominal, p=0.001), WOMAC physical function and BPI interference scales (nominal, p< 0.05).
Moreover, analysis of change from baseline to week-12 for function scales mediated by change in
pain intensity showed that fulranumab treatment also had a significant (nominal, p=0.026) effect on
WOMAC physical function scale that was independent of its effect on pain intensity. Sensitivity
analysis confirmed primary findings.
Conclusions: In patients with chronic osteoarthritis pain, improvements in physical function in
response to fulranumab treatment are correlated with the extent of pain relief. However, functional
improvements are not mediated entirely through pain relief, but are also a result of direct effect on
physical function. Safety results were previously reported.
773
CLINICAL CHARACTERISTICS OF POST-CRANIOTOMY HEADACHES AFTER
NEUROVASCULAR DECOMPRESSION IN THE POSTERIOR FOSSA
1
V. Viswanathan , K. Slavin
1
2
2
University of Illinois at Chicago, Department of Neurosurgery, University of Illinois at Chicago,
Chicago, IL, USA
Background: Retrosigmoid approach (RSA) is sometimes associated with persistent post-operative
headaches (POH). This topic is described primarily in vestibular schwannoma (VS) patients.
Investigations on POH following microvascular decompression (MVD) surgery do not detail headache
(HA). We describe and categorize POH that developed in our MVD patients.
Methods: Medical charts of 54 adult patients who received MVD with bone putty cranioplasty for
trigeminal neuralgia (TGN), geniculate neuralgia (GN), hemifacial spasm (HFS) or glossopharyngeal
neuralgia (GPN) were reviewed for development of POH. All procedures and follow up pain
assessments were performed by same surgeon. 5 cases were excluded due to insufficient follow-up.
Results: Post-surgical analysis was performed on 37 female, 12 male patients, mean age 52,
average follow-up 16.1 months. Presenting illnesses were: 43 TGN, 1 TGN-GN, 2 GN-GPN, 3 HFS.
POH were categorized:
Surgical Site Pain (SSP) - 8 immediate, 2 delayed onset;
Cranial Neuralgia - 5 persistent, 13 recurrent, 6 atypical - occurring in other location;
Primary HA-like Syndromes (PHLS) - 9 post-operative, 1 pre-operative onset. 5 patients were
included in all 3 groups and 3 in 2 groups.
8/15 patients with SSP or PHLS had neuralgic pain. All SSP resolved without intervention. PHLS
resolved in 6/9 with medical management.
Conclusions: Patients with SSP and PHLS demonstrate excellent recovery with low incidence of
long-term HAs following MVD. However, the persistence/recurrence of neuralgic pain may be
associated with development of other POH types. A new uniform POH classification following RSA
may lead to better estimation of surgical outcomes, improving patient preparedness.
774
POSTOPERATIVE PAIN CARE IN NURSE PRACTICE IN LATVIA
1
1
1
1
I. Strode , I. Dupure , L. Afremovics , S. Seimane , I. Logina
1
2
2
P. Stradins Medical College of the University of Latvia, Jurmala, Department of Neurology, Riga
Stradins University, Riga, Latvia
Background and aims: To provide patient's comfort one of the most significant tasks in the
postoperative period is to relieve surgical patient's pains. The aim of the study to assess
responsibilities of nurses and appropriate professional competency in biopsychosocial care of
postoperative pains.
Methods: Survey utilizes quantitative research method. As an investigation tool is chosen
questionnaire. Survey was carried out in the surgical profile and intensive care wards in Riga and
regional clinics of Latvia. Questionnaire embraced 730 nurses, 163 physicians and 602 surgical
patients with an acute pain syndrome.
Results: Based on use of factor analysis method, nurses' and physicians' research group identified
correlated groups of nurses' duties. Five basic categories of nurses' duties were determined assurance of designated drug therapy, information of patients and general care, evaluation and care
of symptoms directly connected to pain, evaluation of pain intensity and patients' condition. In nurse
group action was recognized as organized and planned by 54,4% of surveyed nurses, 45,6% of
nurses note unorganized pain assessment activities in patient care. Nurses which noted pain
assessment as a planned activity in patient care mostly accentuated use of Visual analogue scale
(p=0.003), Verbal pain assessment scale (p=0.000).
Conclusions: In postoperative patient care are secured discharge of duties associated with medical
therapy, provision of patient's physical and psychological comfort, lower assessment is for care
activities connected with the evaluation of patient's pain and associated symptoms. Only partial
documentation about the assessment of pain patient condition exists in nursing practice.
775
FACTOR ANALYSIS OF THE GERMAN VERSION OF THE MCGILL SHORT-FORM PAIN
QUESTIONNAIRE
1
1
2
2
M. Hornyak , B. Klasen , D. Riemann , H. Scholz , R. Thoma
1
1
2
Algesiologikum - Zentren für Schmerzmedizin, München, Universität Freiburg, Freiburg im Breisgau,
Germany
Background: The Short-Form McGill Pain Questionnaire (SF-MPQ) is validated and internationally
used for the assessment of pain intensity and pain quality. In the English version, a two factor model
of sensory and affective pain dimensions and an alternative model of sensory and sensory-affective
dimensions of pain qualities were proved. In the present study we evaluated these models in the
German version of the questionnaire.
Methods: Data of 732 consecutive patients with chronic pain from two German centres were studied.
Results: The confirmatory factor analysis showed a very low global model-fit with the postulated
original model (χ ² = 476 105, p = 0.001, RMSEA = .077, 90% CI .070 - .084, CFI = .81, SRMR =
.062). The alternative two-factor model yielded a better fit to the data (χ ² = 89 026, p = 0.0019,
RMSEA = 0.071, 90% CI .057 - .086, CFI = .925, SRMR = .043). In both models, the local model fit
was low.
Conclusions: The original model by Melzack showed a low model fit in our data set. In contrast, the
alternative model by Beattie and coworkers with sensory and sensory-affective pain descriptions had
an acceptable to good model fit. Influences of cultural differences concerning the interpretation of pain
sensations and the nature of the investigated pain conditions are possible. The higher homogeneity of
the affective factor indicates that the affective dimension of pain sensation is similar in all patients
regardless of their location and pathogenesis of the pain.
776
PAIN ASSESSMENT ABILITIES OF NURSING STUDENTS: THE DIFFERENCE BETWEEN FIRST
AND SECOND YEARS
S. Ünver, S. Yıldızeli Topçu, Ü. Yıldız Fındık
Trakya University Health Science Faculty, Edirne, Turkey
Background and aims: Pain is an uncomfortable feeling in the body and difficult for clinicians also for
nursing students to measure objectively. For reducing pain, a systematic process of pain assessment
should start with a qualified measurement and finish with an effective re-assessment.
Objectives: This descriptive study was carried out to determine the pain assessment abilities of
nursing students and the differences between their first and second year of clinic experience.
Methods: In this study; 229 nursing care plans were investigated between September 2011-May
2013. The data were collected from the same students' nursing care plans during their first year and
second year in nursing training.
Results: It was found that 67.6% of nursing plans were done in surgical clinics and 128 students
diagnosed the pain as a nursing diagnosis. 65.6% (84/128) of the students belonged to second year
and took medical-surgical courses. There was a significant difference between first and second year
students' status of diagnosing pain in their nursing care plans (p< 0.001).When the first year students
were diagnosing pain according to patients' self-report, the second year students were doing it
according to patients' body expressions.Only six of the students mentioned about the severity of pain
and five of them were second year students. 41.6% of the students had used no pain scale to assess
pain.
Conclusions: This study showed that students didn't appear to retain the pain assessment
knowledge even the patient was post-operative and students preferred only writing the nursing
diagnosis.Adding special topics to the lessons about pain assessment and scales can be a solution.
777
AUTOMATED CLASSIFICATION OF PAIN INTENSITY BASED ON DATA FROM BIOPOTENTIALS
AND VIDEO DATA FROM FACIAL EXPRESSION AND HEAD POSE
1
1
1
1
1
2
2
S. Walter , S. Gruss , J. Tan , K. Limbrecht , H.C. Traue , A.O. Andrade , G. Moreira da Silva , P.
3
3
Werner , A. Al-Hamadi
1
Department Psychosomatic Medicine and Psychotherapy, University of Ulm, Ulm, Germany,
Biomedical Engineering Laboratory (BioLab), Federal University of Uberlandia, Uberlandia, Brazil,
3
Institute for Electronic, Signal Processing and Communication, University of Magdeburg, Magdeburg,
Germany
2
Background and aims: The objective diagnosis of subjective, multi-dimensionally experienced pain
has not been adequately solved, particularly in subjects, who are unable to use traditional pain scales.
Aim of the study is to advance an automated pain recognition system using biopotentials and video
data from facial expression and head pose.
Methods: 90 participants where stimulated with 80 painful heat stimuli (four levels between pain
threshold and tolenrance by Medoc Pathway Cheps). The classification procedure (support vector
machine) made use of biopotentials (25 channels, 156 features) and facial expression and head pose
(4 cameras, 326 features) (see figure 1).
[Figure 1. Experimental Design]
Research questions: What kind of features and feature patterns are most relevant for a robust pain
intensity recognition? Which kind of multimodal data fusion has the most robust pain recognition
output (see figure 2)?
[Figure 2. Fusion ]
Results: 80% of the four pain levels were correctly identified with the total amount of features from
biopotentials (amplitude, frequency, stationarity, entropy, similarity, linearity) and respectively from
facial expression combined with head pose. Effectiveness of feature combination for classification is
in progress. The results of different data fusion methods will be discussed.
Conclusions: All in all, we are advancing towards our vision of an automatic system for an objective
measurement of pain which will facilitate pain monitoring, logging and support in a clinical
environment.
778
VALIDATION OF THE ADI SCORING SYSTEM TO EVALUATE COLD HYPERALGESIA
1
1
2
A. Wright , P. Moss , H. Benson
1
2
School of Physiotherapy, School of Pharmacy, Curtin University, Perth, WA, Australia
Background and aims: Subjects with cold hyperalgesia exhibit differences in sensory experience as
well as pain response. A new scoring system - Algotect Detection Index (ADI), combines measures of
cold intensity and quality. The aim was to validate the ADI scoring system using thermal cold stimuli.
The ability of the ADI to discriminate between sustained cold stimuli was assessed. Criterion validity
was assessed by comparing ADI score with McGill Pain Rating (PRI) Index score.
Methods: Twenty-nine volunteers participated in the study. Testing was performed on the volar
surface of the dominant forearm. CPT was measured in triplicate (Medoc TSA II thermode). Subjects
were divided into groups according to CPT< or>15˚C. Three sustained cold stimuli (10˚C, 15˚C and
20˚C) were applied for five minutes each. Subjects completed VAS for intensity of cold, heat,
unpleasantness and pain every 30 seconds. Every one minute, subjects selected words to describe
the sensation experienced.
Results: There was a significant difference in ADI between temperatures (p< .001). The ADI
components also showed significant temperature-dependent effects. ROC analysis showed ADI was
a more accurate predictor of CPT group (< >15˚C) than PRI: AUC .832, sensitivity .90, specificity .74,
cut-off score 4.9. Subjects with CPT>15˚C exhibited significantly higher ADI scores at 10˚C and 15˚C.
Conclusions: The ADI showed good discriminative ability and good internal construct validity. ADI
was able to predict membership of a cold hyperalgesic group, suggesting that ADI is able to
discriminate between normal and abnormal responses using a cut-off score of 4.9.
779
ARE PAIN AND PHYSICAL ACTIVITY INTER-RELATED? THE CASE OF UNIVERSITY
STUDENTS
F. Mutluay, C. Algun, A. Yildiz, G. Ertunc
Physiotherapy and Rehabilitation, Istanbul Medipol University, Istanbul, Turkey
Purpose: This study aims the evaluation of musculoskeletal pain and its relationship with the physical
activity level of physiotherapy students.
Methods: A Pain Assessment Survey questioned pain presence, level and location during the daily
living (ADL) and social activities. Visual Analog Scale was used for ADL limitation and pain while
physical activity level was assessed with the FIT score.
Results: 121 students (31 males) aged 18-25 participated to the study. 101 students (83.5%) felt
some pain with 47 (females: 31) experiencing multi-location pain. FIT scores were found to be poor
(31.0±22.7) and were stronger but not significantly so for males (36,9±26,8) than for females
(29,9±26.0). Pain localisation indicated 78% back, 35% lower and 27% upper extremity pain. No
gender related differences were found for single and multi-location pain distribution, Females
experienced more pain than males but not significantly so. No relationship between FIT scores and
any of pain-related parameters were found. Walking limitation correlated marginally with pain duration
(rp=0,179 p< 0,048) and weakly with back pain presence (r=0,2 p< %5). ADL limitation was correlated
with lower extremity pain (rp=-0,221 p< 0,015), sleep quality (rp=0,226 p< 0,013), more strongly so
with walking limitation (rp=0,270 p< 0,003) and social interaction limitations (rp=0,598 p< 0,0001).
Conclusion: Given our subjects poor FIT scores reflecting their low physical activity level and their
very high incidence of pain, some correlation was suspected to exist between these parameters; our
study negates this suspicion and points to their independence in this age group.
780
NURSES´ AWARENESS AND ATTIDUDES OF PAIN CONTROL IN TURKEY
1,2
S. Yildizeli Topçu , D. Oztekin
1
3
2
Nursing Department, Trakya University Health Science Faculty, Edirne, Surgical Nursing, Istanbul
3
University Institute of Medical Sciences, Surgical Nursing, Istanbul University, Nursing Faculty,
Istanbul, Turkey
Background and aims: Despite the importance of patient satisfaction, inadequate pain management
continues to be a significant problem in the patient care. The aim of this study was to determine the
nurses' awareness and attitudes of pain control in Turkey.
Methods: This descriptive study carried out between 13 March 2013 and 30 April 2013 was included
72 nurses from different regions of Turkey who can be contacted via e-mail and social media. A
questionnaire prepared by the researchers was used for collection of data.
Results: It was found that 75% of nurses was undergraduate degree, half of the nurses were living
big cities such as İstanbul, İzmir and Ankara, 55.6% have pain experiences due to surgery or trauma
and 56.4% thought that nurses have most important role in pain control. It was determined that 44.8%
of nurses recognized the pain with behavioral changes, 28.8% were used pain scale for assessing the
pain, most of them preferred application of analgesics for controlling pain, 91.7% did not participate in
any training programme for pain control, 23.6% used positioning as a nonpharmacological method
and 27.8% of the nurses reported that the most important difficulty in the pain control was not be
informed by the patients about pain.
Conclusions: Considering the nurses' roles in pain control, it was recommended that nurses should
take professional training about pain control and follow the latest development. Evaluation of the
patient satisfaction of pain management is thought to be guidance for nurses.
781
PAIN MANAGEMENT IN KOSOVO - CHALLENGES AND ACTIVITIES
1
2
1
A.J. Bytyqi , F. Kryeziu , A.L. Bytyqi , B.F. Sylaj
1
1
2
Anesthesiology and ICU, -, Regional Hospital 'Prim.Dr.Daut Mustafa', Prizren, Kosovo
The main purpose of the Association is to advance and modernize in 2 segments of activity:
Education and Science.
In PHA program are planned to develop many activities such as:
- The organization of various structured courses,
- Awareness and education of patients and medical staff
- Treatment and Management of Pain
- Establish standards and protocols in health care for the treatment and management of pain
- Organization of activities: Workshops and Symposiums for pain management.
- Development of public policies relating to the treatment and management of pain.
- Publication of leaflets and information brochures for health education of the population about the
problems with pain management.
- Continuing professional education of doctors and nurses with new achievements in medicine for
diagnosis, treatment and management of pain.
- Publication of scientific professional journal that deals with the problems of diagnosis, treatment and
management of pain, for the study of doctors and other professionals which represent the work inside
and outside Kosovo.
- Cooperation with similar associations in the world.
- Teamwork only way of working.
1088
EVALUATION OF AETIOLOGIES OF CHRONIC LOW BACK PAIN WITH DIAGNOSTIC BLOCKS
1
2
C.K. Chen , V.E. Phui , A.J. Nizar
1
3
2
Anesthesiology and Pain Management, Normah Medical Specialist Centre, Medicine, Sarawak
3
General Hospital, Kuching, Anaesthesiology and Intensive Care, Hospital University Science
Malaysia, Kubang Kerian, Malaysia
Background: Determination of causes of chronic low back pain remains a challenge in clinical pain
practice, as various structures in low back can be the pain generator. Performing a diagnostic block to
a main pain generator allow one to generate concomitant pain, and at the same time, to inject local
anaesthetic, in order to confirm the source of pain. The purpose of this study was to determine the
aetiologies of chronic low back pain by utilizing diagnostic blocks.
Methods: In a prospective evaluation, 105 patients with the chief complaint of low back pain with a
visual analogue score of 4 and above, lasting longer than 3 months were evaluated with diagnostic
blocks, which include medial branch blocks, sacroiliac joint injections, provocative discography,
selective nerve root blocks and piriformis muscle injections. Patients with more than 50% pain relief
after injection fulfilled the diagnostic criteria.
Results: A total of 140 diagnostic blocks were performed. Eighty-one patients had only one aetiology
while 16 other patients had more than one aetiology for chronic low back pain. Diagnostic blocks for 8
patients failed to fulfil diagnostic criteria, thus aetiology for low back pain was undetermined. Out of
105 patients, 51% were diagnosed to have facet joint pain, 22% had discogenic pain, 19% had
sacroiliac joint pain and 18% had piriformis syndrome.
Conclusions: Facet joint pain was the most common aetiology for chronic low back pain. Targetspecific treatment is possible when the actual cause of low back pain is determined by diagnostic
block.
1089
QUANTITATIVE SENSORY TESTING AFTER WRIST AND ANKLE FRACTURE
1
2
2
3
4
2
5
6
J. Hall , S. Nelson , J. Bailey , J. Rowett-Harris , P. Tarassoli , S. Palmer , A. Goebel , R. Atkins , C.
2,7
McCabe
1
2
Bath Centre for Pain Services, Royal National Hospital for Rheumatic Diseases, Bath, Faculty of
3
4
Health and Life Sciences, University of West of England, Limb Reconstruction, Bristol Royal
5
6
Infirmary, Bristol, Walton Centre, University of Liverpool, Liverpool, Roger Atkins, Limb
7
Reconstruction, Bristol Royal Infirmary, Bristol, Bath Centre for Pain Research, Royal National
Hospital for Rheumatic Diseases, Bath, UK
Background and aims: Wrist and ankle fractures are common injuries worldwide. Mkandawire
(2002) reports that < 60% of limb fracture patients experience long-term disability and chronic pain.
Chronic pain is often associated with sensorimotor dysfunction but little is known about the early
impact of fractures on these systems.
The aim of this pilot was to identify somatosensory changes in the acute post-fracture period of wrist
and ankle fractures and how this related to later function, mood and quality of life.
Methods: Patients with unilateral unstable ankle or wrist fracture underwent Quantitative Sensory
Testing (QST) of pressure and cold pain in the affected and unaffected hand/foot at approximately 6
weeks after injury. Self-report questionnaires captured function, mood and quality of life at 6 weeks
and at 6 months.
Results: 53 patients (mean age 54.2 years (SD 17.7), 17 males, wrist fracture=36, ankle= 17)
participated. Median pressure pain was significantly lower in the affected limb (p=0.007). A significant
decrease in cold pain threshold was noted in the affected limb (p=0.0.1). No significant correlations
between QST variables and self report questionnaires were noted at 6 weeks/months (all p>0.05).
Conclusions: Heightened somatosensory sensitivity in acute post-fracture limb is common. The
presence and severity of these symptoms is not prognostic for long-term functional outcome. QST
changes have previously been reported in chronic pain conditions but not post-fracture cohorts. QST
was collected at one time point, further research is needed to confirm these findings and establish
how long these changes in sensory processing continue post-fracture.
1090
RELIABLE VIBRATION STIMULATION COMBINED WITH PRESSURE ALGOMETRY
D. Adnadjevic, T. Graven-Nielsen
Health Science and Technology, Aalborg University, Aalborg, Denmark
Aims and background: The adequate mechanical stimulus condition for exciting deep-tissue
nociceptors is unclear. During palpation the stimulus intensity is alternating suggesting that minor
standardised variations of the pressure intensity during pressure algometry may optimize the stimulus
efficacy. This study examined the outcome and reliability of a novel pressure algometer exerting
vibratory stimulation on top of the fundamental pressure.
Methods: In twenty-four healthy subjects (12 females) pressure pain thresholds (PPTs) were
2
assessed with a linear pressure gradient of 30 kPa/s applied by a 1 cm probe bilaterally on the tibialis
anterior muscle. During constant pressure stimulation (5 sec, 125% PPT) vibrational stimulations of
15, 25, and 50 Hz were applied. Subjects rated their pain perception on a 10 cm visual analogue
scale (VAS) on two occasions separated by at least one week period.
Results: VAS scores during vibrational stimulation (on average 5.5, 5.5, 5.5 cm for 15, 25, 50 Hz,
respectively) were significantly reduced compared to the non-vibration stimulations (5.9 cm; F (3, 21)
= 3.96, P = 0.02). Test-retest relative reliability findings showed intraclass correlation coefficient of
0.70 and the coefficient of variation was 17 % for the VAS scores and no systematic difference was
found between the stimulus modalities.
Conclusions: Vibrational stimulation can be exerted reliably by the new computer-controlled pressure
algometer. In contrast to a more efficient pressure stimulation approach as hypothesised the inhibitory
effect of vibrational stimulation on pressure pain perception verified the inhibitory interaction between
simultaneous pressure stimulation of low-threshold mechanoreceptors and nociceptors.
1091
CHRONIC PAIN PATIENTS WITH A COMORBIDITY OF PTSD REFERRED TO
MULTIDICIPLINARY PAIN REHABILITATION - A 1-YEAR COHORT STUDY
1
2
L.-A.C. Andersen , T.E. Andersen , P.G. Andersen
1
3
2
University of Southern Denmark, Faculty of Health Sciences, University of Southern Denmark,
University Hospital Odense, Odense, Denmark
3
Background and aims: A study in multidisciplinary pain clinics in Finland and Denmark 2009-10,
showed a PTSD prevalence between 21-24%.
The aim of this study is to investigate the impact of PTSD on outcome of multidisciplinary pain
rehabilitation.
Methods: All 285 patients in the Study were referred consecutively for 12 months, 194 participated
and completed the PTSD measure and baseline outcome measures used in the study. 95 were
referred to multidisciplinary treatment and of those 46 completed a final questionnaire at termination
of their treatment.
Physical and mental health was measured with the Medical Outcomes Study 36 Item short-form
Health Survey (SF-36).
Results: The prevalence of PTSD in the total sample was 26,3%. Baseline outcome showed that
patients with PTSD did not differ significantly from patients without PTSD on any of the physical
outcome measures, on the psychosocial outcomes, they experienced a significant poorer general and
mental health as well as an inferior social functioning, reported poorer sleep quality, more cognitive
problems and used more antidepressant medication.
The Physical component scale (SF-36) showed a large reduction after multidisciplinary treatment, but
equal effective for the two groups. The Mental component scale (SF-36) showed a large reduction
after rehabilitation. Comparing those with and without PTSD, the results indicated that the intervention
was slightly more efficient for the group with PTSD.
Conclusion: Multidisciplinary pain rehabilitation was overall equal efficient for chronic pain patients
with or without PTSD. The study highlights the importance of including comorbid chronic pain patients
in multidisciplinary pain rehabilitation.
1092
THE RESPONSIVENESS OF THE ROLAND MORRIS DISABILITY QUESTIONNAIRE IS NOT
INFLUENCED BY THE LEVEL OF KINESIOPHOBIA AT THE BASELINE
E. Cruz, R.N. Fernandes
Physiotherapy, School of Health Care - Polytechnic Institute of Setúbal, Setubal, Portugal
Background and aims: Minimal clinically important difference (MCID) has been defined as the
minimal change in the score that is meaningful for patients. No data on the influence of kinesiophobia
on MCID is available. This study aimed to determine if MCID values were different in the subset of
patients with chronic low back pain (CLBP) who reported high and low levels of kinesiophobia at the
baseline.
Methods: A prospective cohort study of 93 CLBP patients undergoing a multimodal physiotherapy
treatment. At baseline participants completed the portuguese versions of the Roland and Morris
Disability Questionnaire (RMDQ-PT) and the Tampa Scale of Kinesiophobia (TSK-13-PT). Six weeks
later, all the participants completed the RMDQ-PT and a 7 points Global Transition Scale. Receiver
operative characteristic curve analysis was used to determine the ability to detect change in activity
limitation. The effect of kinesiophobia baseline scores on the data was subsequently re-analyzed on
sub-groups of the full cohort according to the median level of kinesiophobia at the baseline.
Results: The RMDS-PT showed superior discriminative abilities in patients with higher levels of
kinesiophobia (area under the curve ranging from 0.69 to 0.55 in the case of TSK-13-PT > 32, and
TSK-13-PT < 32). The MCID obtained for RMDQ-PT in the whole cohort (1.5) remained constant for
patients with high (63.2% sensitivity, 81.8% specificity) and low (60.4% sensitivity, 81.8% specificity)
levels of kinesiophobia at baseline.
Conclusions: RMDQ-PT ability to detect change in activity limitation in patients with CLBP was not
affected by kinesiophobia baseline scores.
1093
PAIN EVALUATION IN PATIENTS AFTER CARDIAC SURGERY INTERVENTION. RELATIONSHIP
AMONG GRAFTING TYPE USED, AGE AND SEX
1
2
3
1
N. Filipi , K. Filipi , S. Methasani , A. Disani , M. Kolotourou
1
2
3
3
Europian Hospital Tirana (GVM Care & Research), Institute of Public Health (ISHP) Tirana, Hygeia
Hospital Tirana, Tirana, Albania
Objective: The purpose of the study was to investigate patients' perceptions and effectiveness of a
pain management regimen, which consisted of intermittent doses of morphine, in the critical care unit
after cardiac surgery.
Design: Pain evaluation and other vital signs, were performed every two hours beginning at the time
th
of the patient's extubation and continuing up to the 30 hour after the surgery.
Patients: 102 patients of three private hospitals in Tirana, Albania, during the period 2008 -2013
(24.5% females and 75.5%males; mean age 61 years) who underwent cardiac surgical procedures.
Inclusion criteria were patients submitted to elective cardiac surgery and ASA lower than 5; patients
extubated up to 12 hours after the anesthesia effect wore off; no allergies; adequate comprehension
and verbalization skills. Exclusion criteria: patients hemodynamically instable, systolic arterial
pressure lower than 90 mmHg, massive hemorrhage, and cardiopulmonary arrest; when discharged
from the ICU earlier than 30 hours after extubation.
Results: Total amount of morphine received was (mean = 26.7 mg; SD = 13.3; range: 0-68). Patients
requiring an internal mammary artery graft experienced increased pain despite greater amounts of
morphine. Elderly patients received less morphine and refused pain killers more often than younger
patients. Females' pain experience was less acceptable than among males. Less than half of the
participants communicated pain experience to nurses.
Conclusion: It's necessary to improve, the pain assessment and management in relation to gender,
age differences and type of graft/s used; morphine administration before activity and the
communication of pain experience by patients.
1094
DETERMINING THE MINIMAL CLINICALLY IMPORTANT CHANGE IN QUALITY OF LIFE FOR
PATIENTS WITH NEUROPATHIC PAIN
1,2
2,3
4
1
H. Poole , F. Frank , C. Barker , A. Mavrianou , T. Nurmikko
1
2
2,5
3
Liverpool John Moores University, Pain Research Institute, The Walton Centre NHS Foundation
4
5
Trust, Southport & Ormskirk NHS Trust Community Pain Service, University of Liverpool, Liverpool,
UK
Background and aims: Recent Guidelines for Neuropathic Pain (NeP) assessment (Haanpaa et al
2011) recommend that Quality of Life (QoL) is included as a patient reported outcome in treatment
trials. Data on minimal clinically important difference (MCID) i.e. the smallest improvement patients
perceive as beneficial is not yet established for all measures in neuropathic pain. The Neuropathic
Pain Impact on QoL scale (NePIQoL) is a condition-specific QoL measure. Our primary aim was to
establish the MCID for this scale across a range of NeP types.
Methods: Pragmatic, prospective cohort study with repeated measures. ~300 patients will complete
NePIQoL, SF36, HADS, mBPI, NPSI and sleep scales before and after treatment. Following treatment
a patient global impression of change score (PGIC) is used as the gold standard to determine MCID.
Results: To date, 277 patients, 56% female, mean age 52.57, SD 13.59 years have been recruited
from a specialist pain centre and primary care and provided baseline data. NeP types include;
peripheral neuropathy, posttraumatic neuropathic pain, neuropathic low back pain and trigeminal
neuralgia, post hepatic neuralgia and central pain. Interim analysis of baseline data shows impairment
in QoL associated with different types of NeP. Change in total NePIQoL score is associated with
PGIC (r=.35, p=.002).
Conclusions: Greater post treatment numbers will enable analysis of MCID to provide a benchmark
for use of the NePIQoL in future clinical studies.
1095
TRANSLATION AND TRANSCULTURAL ADAPTATION OF PATIENT NEUROTOXICITY
QUESTIONNAIRE (PNQ)
A.B. Carvalho, J.B.S. Garcia, J.V.F. Ribeiro, T.K.M. Silva, F.J.A. Mesquita, Pain Research Group
Medicine, Federal University of Maranhão - UFMA, São Luís, Brazil
Background and aims: Chemoterapy- Induced Peripheral Neurotoxicity (CIPN) involving sensory
and motor nerve lesion or disease is a common and serious clinical problem that affects many
patients receiving cancer treatment. Thus, it is very important to make available a patient- reported
outcomes (PRO) to overcome the limitation and to able the patient perception about your treatment or
clinical condition.
The aim of this study was to translate and transculturally adaptation Brazilian Portuguese version of
the scales Patient Neurotoxicity Questionnaire (PNQ), a simple, self-reporting tool, to assess the
cancer patients during chemotherapy treatment.
Methods: The PNQ was translated, back-translated, evaluated by a multidisciplinary committee, and
pre-tested. The final version was submitted to field test on a group made uo of 30 subjects with
cancer receiving chemotherapy, were compared and contrasted by a committee composed of
investigators from Brazil and from BioNumerik Pharmaceuticals who developed the scale.
Results: With respect to PNQ the versions one and two had almost 100% semantic equivalence with
original version. After judgement of expert committee, was observed one difficult in the experiential
equivalence. The final stage the pretest, every patients understood all the items.
Conclusion: The translated and tranculturally instruments are presented herein. It is currently
undergoing clinical validation in Brazil.
1096
TRANSLATION AND TRANSCULTURAL ADAPTATION OF PAIN QUALITY ASSESSMENT
SCALE (PQAS)
A.B. Carvalho, J.B.S. Garcia, T.K.M. Silva, J.V.F. Ribeiro
Medicine, Federal University of Maranhão - UFMA, São Luís, Brazil
Background and aims: The majory of patients with cancer are treated with chemotherapy, but the
peripheral neuropathy is a serious and commom problem clinic that affects many patients receiving
cancer treatment. Nonetheless, these symptoms are rarely systematically assessed, leading to delays
in their identification of health professional. The aim of this study was to translate and transculturally
adaptation Brazilian Portuguese version of the scalePain Quality Assessment Scale a simple, selfreporting tool, but isn't specific to assess chemotherapy- induced peripheral neurotoxicity ( CIPN) is a
useful instrument to assess neuropathic pain the cancer patients during chemotherapy treatment.
Methods: The PQAS was translated, back-translated, evaluated by a multidisciplinary committee, and
pre-tested. The final version was submitted to field test on a group made up of 30 subjects with
cancer receiving chemotherapy, were compared and contrasted by a committee composed of
investigators from Brazil and from MAPI Research Trust, who developed the scale.
Results: In the PQAS, the versions one and two had 100% semantic equivalence with original
version. The back translation, however, there was ambiguous wording with the original source
version. After the judgment of expert committee, had difficults in the experiential equivalence and
idiomatic equivalence. During pretest, two people didn't understand the item 12 the scale, but it didn't
interfere in the final version scale.
Conclusion: The translated and tranculturally instruments are presented herein. It is currently
undergoing clinical validation in Brazil.
1097
COMPARING SPANISH AND EU POSTOPERATIVE OUTCOMES USING PAIN-OUT DATABASE.
ANALGESIC CONSUMPTION AND RISK FACTORS FOR WORST PAIN IN POI-SPAIN
J. Garcia-Lopez, I. Serna, M.M. Puig
Pain Research Unit, Dept. Anaesthesiology, IMIM-Parc de Salut Mar, Universitat Autònoma de
Barcelona, Barcelona, Spain
Background and aims: International postoperative data registries with standardized data collection
are optimal to identify sites with poor outcomes, and apply benchmarking to improve results. We
assessed analgesic consumption and risk factors for severe pain (>4) in Spain (POI-Spain), and
compared postoperative outcomes with EU participating hospitals (POI group).
Methods: After informed consent, patients were recruited from general surgery (GS) and orthopaedic
(TR) wards (January-2010 to March-2013). Pain-Out questionnaires /methodology were used
(www.pain-out.eu).
Results: 24,830 patients were enrolled, GS=46.5% and TR=53.5%. POI-Spain registered 4,449
patients (18%) with 53% and 47% in GS and TR, respectively. Overall, pain scores in GS were better
than TR (p< 0.05); the POI-group had the best and worst pain scores. The incidence of AE was low,
and similar in both groups and wards.
In POI-Spain 66% of patients received multimodal analgesia (3.3±0.7 drugs/patient). Most frequent
analgesics were: paracetamol (80.5% of patients), ketoprofen (35.9%), metamizol (28.0%), tramadol
(27.7%) and morphine (27.4%). TR patients received higher doses of paracetamol and tramadol (p<
0.001), while GS received more ketoprofen and morphine (p< 0.03). Multivariate analysis of odds ratio
for developing severe pain was: female gender, chronic pain and type of anaesthesia (p< 0.05).
Conclusions: GS patients reported better pain outcomes than TR. In POI-Spain, multimodal
analgesia with paracetamol ±NSAID ±opioid was used in 66% of patients. Female gender, chronic
pain and general anaesthesia increase the probability to develop severe postoperative pain.
Supported by: EC FP7/2007-2013, Grant No.223590, and Endowed Chair in Pain Management
UAB-Parc de Salut Mar-Menarini.
1098
HCAHPS COMPARATIVE ANALYSIS OF PATIENTS PERCEPTION OF PAIN CARE IN
HOSPITALS IN THE UNITED STATES OVER 6 YEARS
A. Gupta
Anesthesiology, Pain Medicine, Regional Anesthesiology, Drexel University College of Medicine,
Philadelphia, PA, USA
Limited data are available regarding the quality of pain care in the hospitalized patient. This is valid for
data that allow for comparison of pain outcomes from one hospital to another. Such data are critical
for numerous reasons, including allowing patients and policy-makers to make data-driven decisions,
and to guide hospitals in their efforts to improve pain care. The Hospital Quality Alliance (HQA) was
recently created by federal policy makers and private organizations in conjunction with the Centers for
Medicare and Medicare Services (CMS) to conduct patient surveys to evaluate their experience
including pain control during their hospitalization. In January 2012, the results of the Hospital
Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey was released for
review for health care providers and researchers. This survey includes a battery of questions for
patients upon discharge from the hospital including pain-related questions and patient satisfaction that
provide valuable data regarding pain care nationwide from October 2006 to March 2011. This study
will review the results from the pain questions from this available data set and evaluate the
performance of these hospitals in pain care in relationship to patient satisfaction. Furthermore, this
analysis will be provide valuable information on how hospital size, geographic location and practice
setting may play a role in pain care in U.S. hospitals. The results of this study are a representation of
the experiences of patients in U.S. hospitals in regards to pain care specifically and the need for
improved methods of treating and evaluating pain care.
1099
SERVICE EVALUATION ON THE USE OF INTERMEDIATE CERVICAL PLEXUS BLOCK IN
CHRONIC REFRACTORY ANGINA
1
S.N. Jayaseelan , H.K. Tsang
1
2
2
Anaesthesia, Mersey Deanery, Anaesthesia and Pain Management, The Royal Liverpool and
Broadgreen University Hospitals NHS Trust, Liverpool, UK
Background and aims: Stellate ganglion block [SGB] is used traditionally in chronic refractory angina
[CRA] management. Intermediate cervical plexus block [ICPB] has been used with better patient
experience and minimal complications over the last 2 years at the National Refractory Angina Centre
[NRAC] at Liverpool [now known as the Liverpool Angina Management Programme]. The aim of the
survey was to get first-hand feedback about patient experience on ICPB for CRA.
Methods: 17 patients who had previously received SGB but now receiving regular ICPB for CRA
management were asked to complete a questionnaire as part of an approved departmental service
evaluation. Patient feedback was collected on various aspects of their experience over 3 months in
2012.
Results: Anxiety levels were measured on a 10 point scale and were reduced for ICPB. Preoperative:
SGB [range: 4-10, mean: 6.5] & ICPB [range: 0-5, mean: 1.6]. Intraoperative: SGB [range: 0-10,
mean: 7.3] & ICPB [range-0-6, mean: 1.6].
Patients reported a greater than 50% reduction in side effects and complications. 59% reported better
analgesia with ICPB and 41% reported equivalent analgesia between ICPB vs SGB.
100% of the patients rated ICPB as more comfortable compared to SGB and 100% reported that they
would recommend ICPB for a new patient from a patient's perspective.
Conclusions: Based on the patient feedback ICPB is a possible alternative to the SGB for CRA,
providing equivalent analgesia with reduced side effects. Further work is required.
1100
ACUTE POSTOPERATIVE PAIN MANAGEMENT AFTER BREAST SURGERY AND PATIENTS
SATISFACTION
1
2
D. Krleza Supic , S. Misir Situm , G. Brozovic
1
3
2
Anestesiology, reanimatology and intensive care, Univeristy hospital sisters of mercy, Cancer clinic,
University hospital sisters of mercy, Cancer clinic, Zagreb, Croatia
3
Background and aims: evaluation of clinical outcomes in the management of acute postoperative
pain after breast surgery in terms of pain severity, pain relief and satisfaction with pain management
Methods: 100 patients, 33 nurses and 10 surgeons was interviewed. All patients was undergoing
breast surgery and pain management protocol was applied as follows: tramadol 100 mg and
diclofenak 75 mg iv 15 minutes before the end of the surgery, tramadol 100 mg iv 6 hours and
diclofenak 75 mg iv 12 hours after surgery with addition of paracetamol 1000 mg on demand. Next
two days patients were given per os tramadol retard 100 mg twice a day and paracetamol 1000 mg
on demand. The protocol was designed by anesthesiologists. Data were acquired at the end of
hospitalization and three questionnaires was utilized: for patients, nurses and surgeons
Results: the severity of pain was according to VAS scale: < 3 78%, 4-5 14% and > 6 8%. The
satisfaction of pain control was very good in 90 % of patients, 8% was good, and 2 % poor. All ward
nurses (100%) were introduced with pain management protocols, but only 56% have done pain
evaluations. 70% of surgeons were aware of pain protocol but 49% of them were not sure about the
medications and the pain evaluation methods included. 100% of surgeons were convinced of
excellent pain relief on their wards.
Conclusions: additional efforts should be done to achieve better communications among subjects
included in acute postoperative pain management.
1101
VALIDITY AND RELIABILITY OF A GERMAN VERSION OF THE NECK DISABILITY INDEX (NDIG)
1,2
3
J. Swanenburg , K. Humphreys , A. Langenfeld
1
1,4,5
6
, F. Brunner , B. Wirth
7
2
Department of Physiotherapy, Balgrist University Hospital, Department of Rheumatology and
3
Institute of Physical Medicine, University Hospital Zurich, Department of Chiropractic Medicine,
4
University of Zurich and Balgrist University Hospital, Zurich, Switzerland, CAPHRI, School for Public
5
Health and Primary Care, Maastricht University, Maastricht, The Netherlands, Department of
6
7
Chiropractic Medicine, Department of Rheumatology, Balgrist University Hospital, Institute of Human
Movement Sciences and Sport, Eidgenössische Technische Hochschule Zurich, Zurich, Switzerland
Background and aims: The aim of this study was to translate and test the NDI according to
established guidelines into German (NDI-G).
Methods: After translation according to the guidelines in the literature, patients with acute (ACU) and
chronic neck pain (CHR) and a healthy control group (HCG) completed the NDI-G twice with a mean
test-retest interval of 3 days.
Results: The total score of NDI-G showed high reliability (ICC2,1=0.92) and a high Cronbach´s alpha
(α=0.96). The minimal detectable change was 7 points. The Bland-Altman plot revealed a small
positive systematic error of 1.02 points. The Kruskal-Wallis test showed significant differences in the
2
NDI-G total score among the three groups (x =29.77, p< 0.001). The post-hoc Mann-Whitney U tests
showed significant differences in the total score between ACU and HCG as well as between CHR and
HCG (p< 0.001), but not between ACU and CHR (p=0.02). The factor analysis of NDI-G yielded 2
factors that together explained 67% of the variance. Spearman's ρ coefficients showed no correlation
between the NDI-G total score and the VAS in the ACU group (ρ=0.23, p=0.40), and a moderate
correlation in the CHR group (ρ=0.55, p=0.03). The item analysis of the NDI-G revealed moderate to
good reliability for all items. Only the item 'work' could differentiate between the ACU and CHR group.
Conclusions: The NDI-G emerged from this study as a valid and reliable assessment. Its
psychometric properties are comparable with the original version and with validated versions in
various languages.
1102
ACTIVITY MONITORING AS OUTCOME MEASURE FOR NEUROMODULATORY THERAPY
USING SMARTPHONES - A FEASIBILITY STUDY
1
2
2
3
2
2
L.M. Macrea , J. Seiter , S. Feese , O. Amft , B. Arnrich , G. Tröster , K. Maurer
1
1
2
University Hospital Zurich, Institute of Anesthesiology, Wearable Computing Lab, Eidgenössische
3
Technische Hochschule Zurich, Zurich, Switzerland, ACTLab, Signal Processing Systems, TU
Eindhofen, Eindhofen, The Netherlands
Background and aims: Monitoring physical activity has been shown to be an important outcome
measure in the clinical management of chronic pain.
Methods: We performed a feasibility study in two patients with neuropathic pain before and after
neuromodulative therapy using a smartphone system providing physical activity measurements from
acceleration, barometer and location GPS data.
We measured the following smartphone parameters: daily recording time, number of location clusters
visited, number of transitions in between different location clusters, number of steps, number of
instances climbing stairs and the time the patient walked at a certain speed. The clinical evaluation
included: pain intensity, physical functioning and patients ratings of overall improvement. We also
evaluated the health related quality of life.
Results: Our results suggest that the changes in smartphone parameters before and after
neuromodulative therapy were considerable. Improvement of activity was achieved particularly in the
home environment reflected by an increase in walking, a gain in fast cadence activities and a
decrease in rest cadence. Activity questionnaires, however, did not correlate with these
measurements. There was a significant increase in the three clinical core outcome domains and in the
quality of life.
Conclusions: We conclude that smartphone based activity monitoring has the potential to provide
objective intervention outcomes to clinicians with a minimal interference in the patient's daily life.
1103
EFFECTIVENESS AND SAFETY OF LONG-TERM OPIOID THERAPY FOR CHRONIC NONCANCER PAIN
1
2
2
3
1
C. Margarit Ferri , R. Ajo Ferrer , O. Alda Álvarez , M. Lahoz Beneytez , Y. Sastre Peris , J. Román
1
4
Quiles , A.M. Peiró Peiró
1
2
Pain Unit, Hospital General Universitario de Alicante, Foundation for the Promotion of Health
3
4
Research and Biomedicine of Valencia (FISABIO), Universidad Miguel Hernández (UMH), Clinical
Pharmacology, Hospital General Universitario de Alicante, Alicante, Spain
Introduction and objectives: It is well known that prolonged use of opioids can lead to a number of
adverse consequences, associated with the gastrointestinal tract, nervous system, or more long-term
hormonal effects. Evaluation of the effectiveness and safety of chronic opioid therapy was the subject
of this descriptive study.
Methods: During 6 months, 309 chronically treated with opioid were evaluated using validate pain
intensity and relief scale (Visual Analogue Scale, VAS), quality of life (EQ visual analogue scale, EQ
VAS), presence of adverse reactions (ADRs listed), number of medical care visits and prescription
drug plan changes.
Results: Patients (♀ /♂ , 210/99) had predominantly moderate a mean pain intensity (VAS 6.3 score)
with a significant mean pain relief (VAS 3.2) from last visit and a mean quality of life (EQ VAS 45
scores). Any significant difference was found by gender. Most common ADRs were: 58% dry mouth,
43%constipation, 42%nervousness, 41% sexual dysfunction symptoms (19% ♂ erectile dysfunction,
low libido ♂ 23%, ♀ 28%), 34%insomnia and 31% depression. Emergency Department visits
associated more changes in prescription drug plan. A total of 70 ADRs were reported to the Spanish
Pharmacovigilance System.
Conclusions and comments: Opioid analgesics were found to be effective, produced only mild side
effects, without instances of opioid abuse. Control of effectiveness and adverse effects with validated
scales is needed to conduct a proper drug prescription plan, even more, for long-term management of
chronic non-cancer pain.
1104
COURSE OF PAIN AND OUTCOMES OF DEPRESSION AT 6 MONTHS
1
1
2
3
4
J. Hong , D. Novick , W. Montgomery , H. Dueñas , X. Peng , J.M. Haro
1
2
5
3
Eli Lilly and Company, Windlesham, UK, Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia, Eli
4
5
Lilly de Mexico, Mexico City, Mexico, Eli Lilly and Company, Indianapolis, IN, USA, Parc Sanitari
Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona,
Spain
Background and aims: Patients with major depressive disorder (MDD) frequently suffer from
concomitant pain symptoms. This study examined the relationship between course of pain symptoms
and the outcomes of depression
Methods: Data in this post hoc analysis were taken from a 6-month prospective, non-interventional,
observational study that involved 1,549 MDD patients without sexual dysfunction at baseline in twelve
countries worldwide. Depression severity was measured using the Clinical Global Impression (CGI)
and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Pain was
measured using the pain-related items of the Somatic Symptom Inventory (SSI), and quality of life
(QoL) was measured using the EQ-5D instrument with the UK population tariff and the EQ-VAS.
Regression analyses were employed to assess the impact of course of pain on response, remission,
depression and pain severity, and QoL at 6 months, controlling for other baseline patient
characteristics.
Results: Of the 1,117 patients analysed, 541 had no pain, 515 had remitted pain, and 61 had
persistent pain during 6-months. Percentages of patients in remission at 6 months were 80% in no
pain, 83% in remitted pain, and 17% in persistent pain (86%, 92%, and 42% for response). Patients
with persistent pain also had higher levels of depression and pain severity as well as a lower level of
QoL, compared with patients with remitted pain or no pain. Regression analyses confirmed these
findings.
Conclusions: Patients with persistent pain during the treatment of MDD had worse 6-month
outcomes, compared with patients experiencing remitted pain or no pain.
1105
THE BRIEF PAIN INVENTORY XHOSA - TRANSLATION AND VALIDATION FOR USE IN
AMAXHOSA WOMEN WITH HIV/AIDS
1
1
2
R. Parker , J. Jelsma , D. Stein
1
2
Dept of Health & Rehab Sciences, Dept of Psychiatry & Mental Health, University of Cape Town,
Cape Town, South Africa
Background and aims: Standardised measurement instruments which are reliable, valid and have
clinical utility are needed in the evaluation of patients with pain. In South Africa instruments are not
available in several of the indigenous South African languages including isiXhosa. The aim of this
study was to translate and validate the Brief Pain Inventory (BPI) for use in amaXhosa women living
with HIV/AIDs.
Methods: A forward-translation back-translation procedure followed by consensus agreement was
used to translate the BPI. The pre-final instrument was field-tested for acceptability. The BPI-Xhosa
was administered to 170 amaXhosa women living with HIV/AIDS attending a clinic in Cape Town for
treatment. Convergent validity was established by comparing results with the validated EQ-5D-Xhosa.
Confirmatory factor analysis was conducted to determine whether the BPI-Xhosa had a one-, two- or
three-factor structure. Internal consistency was established by calculating Cronbach's alphas.
Results: The use of a graded, 0-10 scale was identified as problematic as graded responses are not
part of Xhosa culture, rather concepts are considered in absolute terms. The BPI-Xhosa
demonstrated excellent convergent validity when compared to the EQ-5D-Xhosa. Confirmatory factor
analysis revealed a two-factor structure (pain intensity and pain interference) for the BPI-Xhosa.
Cronbach's alphas were 0.77 (pain severity subscale) and 0.83 (pain interference subscale) with item
omission having no effect on the underlying construct of the subscales.
Conclusions: This study provides evidence that the BPI-Xhosa is a valid instrument to use in the
assessment of pain intensity and pain interference in amaXhosa women living with HIV/AIDS.
1106
STIMULUS-EVOKED PAIN IN THE FEET: IMPACT ON WALKING SPEED IN TRAUMATIZED AND
TORTURED REFUGEES
A.L. Persson, K. Prip
Research Department, DIGNITY-Danish Institute Against Torture, Copenhagen, Denmark
Background and aims: We recently found no differences in sensory function of the foot soles using
quantitative sensory testing comparing groups of torture victims with or without exposure to falanga
(beatings under the feet). Pain when walking was often associated with hyperalgesia to deep
mechanical pressure and cutaneous hypoesthesia. The aim here was to explore possible relations
between walking speed and pain in the same sample.
Methods: 32 male tortured refugees from the Middle East (mean/median age 45 years) participated;
15 had (F) and 17 had not (NF) been exposed to falanga. Patients were asked about pain in the foot
soles at rest and when walking to determine activity related changes in foot pain. Walking speed was
measured using the timed 10-Meter Walk Test.
Results: The mean walking speed was 1.2 m/s in both groups, slower than average for men in their
40's. Seven F feet and 18 NF feet had no pain at rest. However, all 15 F victims and 13 NF victims
reported pain when walking. More F victims walked with a compensated gait pattern, had a larger foot
pain area and their average foot pain at rest was higher (Visual Analogue Scale; right foot
F/NF=32/24mm; left foot 42/27mm). Also, more F victims reported severe foot pain when walking
(right foot F/NF=12/8; left foot F/NF=14/10).
Conclusions: Ten F and 12 NF victims would not manage to pass a pedestrian crossing during green
light where a walking speed of 1.5m/s is needed, according to the Danish Road Directorate.
1107
SHORT RUN DYNAMICS IN PAIN RELIEF AND HEALTH-RELATED QUALITY OF LIFE IN
PATIENTS WITH OSTEOARTHRITIS: EVIDENCE FROM THE SORT STUDY
1
2
3
4
4
4
4
C.J. Phillips , G. Iolascon , F. Rannou , C.M. Black , S.L. Stokes , P.M. Peloso , P. Mavros , P.
5
6
7
6
4
4
Conaghan , R.A. Moore , M. Van de Laar , N. Arden , S.S. Sen , S.D. Taylor
1
2
3
Swansea University, Singleton Park, UK, Second University of Naples, Naples, Italy, Université
4
5
Paris Descartes, Paris, France, Merck & Co., Inc., Whitehouse Station, NJ, USA, University of
6
7
Leeds, Leeds, Oxford University, Oxford, UK, University of Twente, Enschede, The Netherlands
Background/aims: Clinical manifestations of osteoarthritis (OA) involve pain and functional
limitations that impact HRQOL. The objectives were to assess short run changes in pain relief and its
association with HRQOL in patients with knee OA.
Methods: SORT, a 12-month prospective multinational study enrolled participants with knee OA
receiving analgesics. Inadequate Pain Relief (IPR) was defined as a score of >4, indicating "moderate
or greater pain, on BPI Question “What is your pain on average?”. SF-12 questionnaire was used to
assess HRQOL. Baseline (BL) and month one (M1) data were used to assess short run dynamics.
Short Run
Dynamic
N (%)
Pain Relief
Status
Baseline
Month 1
PCS Score, PCS Score, p value
mean (SD) mean (SD)
Baseline
MCS
Score,
mean (SD)
Month 1
MCS
p value
Score,
mean (SD)
Improved
Response
(IPR to
non-IPR)
158 (13.7)
38.68
(8.16)
40.57
(7.29)
0.0014
48.29
(11.27)
50.2 (9.01) 0.0153
Remained
Inadequate
455 (39.5)
(IPR to
IPR)
34.02
(7.64)
34.39
(6.55)
0.3045
44.69
(11.18)
42.42
(9.82)
<0.0001
Decreased
Response
163 (14.1)
(non-IPR to
IPR)
38.95
(8.38)
36.96
(7.09)
0.0009
51.34
(9.95)
48.92
(9.42)
0.0015
Remained
Adequate
377 (32.7)
(non-IPR to
non-IPR)
42.56
(7.89)
42.52
(7.35)
0.6825
52.31
(8.48)
51.14
(8.42)
0.0015
[Short run changes in pain relief and SF-12 Scores]
Results: 1153 participants were included: 67.3% women; mean age 68 years (SD=9.4); mean OA
duration 5.9 years (SD=6.2). Over one month, 28% reported changes in pain relief. Short run changes
in pain relief status were positively associated with changes in both the physical (PCS) and mental
(MCS) components of SF-36 (see table). While there were no significant differences in the PCS score
for those not changing pain relief status in the short run, the MCS score showed a significant
decrease for the same group which merits further examination.
Conclusions: The short run changes in pain relief are positively associated with changes in HRQOL.
1108
PREDICTORS OF PAIN SIX MONTHS AFTER MUSCULOSKELETAL TRAUMA - TOWARDS
PREVENTING CHRONIC PAIN
1
1
2
3
J.G.J. Pierik , M.J. Ijzerman , A.B. Van Vugt , M.M.R. Vollenbroek-Hutten , C.J.M. Doggen
1
1
Health Technology & Services Research, MIRA Institute for Biomedical Technology and Technical
2
Medicine, University of Twente, Emergency Department and Department of Surgery, Medisch
3
Spectrum Twente, Biomedical Signals and Systems, MIRA Institute for Biomedical Technology and
Technical Medicine, University of Twente, Enschede, The Netherlands
Background and aims: Acute musculoskeletal pain is one of the primary complaints of patients in
the Emergency Department (ED). Multiple factors within this acute pain phase may be responsible for
transition from acute to chronic pain. The aim is to find prognostic factors that will give us the ability to
target high-risk patients in the emergency setting and provide them with appropriate treatment to
prevent chronic musculoskeletal pain.
Methods: In a prospective cohort study (PROTACT) adult patients with injury due to blunt trauma to
the extremities of the musculoskeletal system who attend the ED of Medisch Spectrum Twente, the
Netherlands were followed for six months. Characteristics of patients, including psychosocial-,
biomedical and health related factors, and perception of pain were collected from hospital registration
and questionnaires at ED-visit, 6 weeks- 3 -and 6 months follow-up.
Results: From September 2011 till March 2012, 250 patients (58.8% women; mean age=46.0)
attended the ED and were followed for six months. Prevalence of pain (NRS >=1) six months after
injury was 43%. Women [Adjusted odds ratio (ORadj)=1.41(95%CI 0.71-2.77)], severe pain at EDdischarge [ORadj=3.03 (95%CI 1.07-8.64)], anxiety [ORadj=3.12 (95%CI 0.98-9.94)], Kinesiofobia
[ORadj=2.16(95%CI 1.10-4.24)] and presence of chronic pain [ORadj=2.55(95%CI 1.12-5.81)] were
found to be independent predictors of pain at 6 months.
Conclusions: In the PROTACT-study 43% of patients still have pain six months after trauma.
Potentially modifiable factors, such as severe pain at discharge, kinesiofobia and anxiety might be
addressed through intervention in emergency setting to prevent chronic pain.
1109
AN AUDIT OF PERI-OPERATIVE JOURNEY OF PATIENTS UNDERGOING PRIMARY
ARTHROPLASTY AT ROYAL INFIRMARY EDINBURGH
1
2
3
3
S. Ramaswamy , B. Crockett , A. Paul , K. Carey
1
2
3
Pain Clinic, Charing Cross Hospital, London, University of Edinburgh, Anaesthetic Department,
Royal Infirmary Edinburgh, Edinburgh, UK
Background and aims: Enhanced Recovery After Surgery (ERAS) protocols are increasingly used in
number of hospitals for total hip and knee arthroplasty (THA and TKA). At the time of initial ERAS
implementation, we aimed to look at the perioperative and 6 week outcome of patients in our hospital.
Methods: After getting hospital ethics approval, we used an 'anaesthetic data sheet', 'patient diary'
and '6 week follow-up' questionnaire to get the outcome information.
Results: Anaesthetic Data Sheets were completed by 154 patients. Of these 67 patients completed
voluntary diaries detailing their experience and 64 patients completing the 6 week questionnaire.
There was no difference in the baseline characteristics between patients.
There was no significant difference in length of stay in recovery or hospital, pain scores, blood loss,
mobilisation, catheterisation, transfusion, readmission or mortality. Patients in ERAS pathway
undergoing TKA had a significantly lower incidence of nausea and vomiting (PONV) (P= 0.044).
The patient outcome at 6 weeks is outlined in Table1 and 2.
Patients with pain (%)
Average VAS
No patients VAS ≥40 (% No patients S-LANSS
with pain)
≥12 (% of total
14 (48.3)
24.1
3 (10.3)
2 (8)
[Post THA 6-week followup (29 patients)]
Patients with pain (%)
Average VAS
No patients VAS ≥40
(%)
No patients S-LANSS
≥12 (% of total)
24 (68.6)
39.1
12 (34.3)
14 (40)
[Post TKA 6-week followup (35 patients)]
Conclusions: At the time of implementation of ERAS, there were no major differences in patient
outcomes in patients undergoing arthroplasty apart from PONV in TKA patients. Substantial number
of patients have pain at 6 weeks. Patients following TKA have more intense and neuropathic type
pain.
1110
POTENTIAL PREDICTORS OF INTENSITY OF MULTIMODAL PAIN THERAPY
A.-M. Schneider, B. Klasen, C. Schiessl, R. Thoma
Algesiologikum - Zentren für Schmerzmedizin, München, Germany
Background: The Algesiologikum group treats patients with chronic pain in three urban (Munich) and
one rural (Vilsbiburg) in-patient pain medicine centres. Patients in so-called “open groups” should take
part in the multimodal pain therapy (MMPT) as intensive as possible. Up to now, little is known about
the relation between “dosage of therapy” and pain or psychological characteristics respectively. The
aim of this study was to evaluate the relation between pain characteristics, psychological predictors
and the dosage of multimodal pain therapy of patients within most commonly diagnoses (F45.41;
M53.1; M54.4; M54.5; M79.10; M79.70; M96.1).
Methods: Patient sample included 434 patients in 2012. Pain characteristics (Mainz Pain Staging
System MPSS) and psychological data were collected with the German Pain Questionnaire 2007
(http://www.dgss.org/fileadmin/pdf/12_DSF_Anamnese_Muster_2012.2.pdf,
called
3.5.13).
Furthermore DRG-Data were collected by so-called §21-data-sets.
Results: We found significant correlations between the dosage of MMPT (one therapeutical
unit=30Min) and Chronic Pain Grade (CPG;von Korff: 1992), (Spearmans Rho=.298, p< .001), but not
between MMPT and MPSS, p>.05 or quality of pain (SBL; Korb, Pfingsten: 2003). Regarding
psychological variables, anxiety (HADS, Zigmond;Snaith: 1983) shows a significant correlation to the
dosage of multimodal pain therapy, Depression (HADS) and general well-being (FW7; Herda et al.:
1998) do not. Further significant correlations were found in between actual, mean and maximum
intensity of pain and HADS, SBL and FW7.
Conclusions: We found significant correlations between dosage of MMPT and CPG and anxiety.
Surprisingly no correlations were found between FW7 and MMPT as well as depression and MMPT.
Further questions about patient assignment to the right dosage of MMPT arise throughout the
presented results.
1111
MASTICATORY EFFICIENCY IN ASYMPTOMATICS INDIVIDUALS FOR TMD TRIAGED BY RDC /
TMD AND ELECTROMYOGRAPHY
1
1
1
1
2
M.S. Cazal , A.M.B.R. Silva , A.A. Junqueira Junior , M.D.O. Melchior , W. Mestriner Junior ,
1
M.A.M.R. Silva
1
2
Department of Restorative Dentistry, Department of Stomatology, Public Health and Forensic
Dentistry, Faculty of Dentistry of Ribeirão Preto - University of São Paulo, Ribeirão Preto, Brazil
Background and aims: Electromyography (EMG) has been widely used in research, being
recognized as a valid method for assessing the function of the muscles of mastication and has been
correlated with masticatory efficiency (ME). The aim of this study was to analyze the ME, from the
selection of a population of young adults asymptomatic temporomandibular dysfunction (TMD)
screened the RDC/TMD and EMG.
Method: 30 individuals, young adults of both genders, with a mean age of 23.46; triaged as
asymptomatic for TMD from the RDC/TMD and EMG (Freely, DeGötzen, Milano, Italy) during the
proofs of (1) maximal clench with cotton, (2) maximal clench in habitual occlusion. Subsequent
examination of the ME during normal mastication (H), right (R), left (L), with assessment system
Masticatory Efficiency (beeds - FCFRP and FORP/USP).
Result: Subjects were classified as asymptomatic for TMd from the RDC/TMD and after EMG
showed values appropriate to this classification: POC temporal (86.69 ± 3.2%); POC masseter (86.10
± 2.56%); TORQUE (0.95 ± 4.78%), AS (-0.23 ± 7.71%); IMPACT (106.35 ± 33.91%). Subsequently,
the beeds were processed and Evaluated by the colorimetric method, we obtained value for the
fuccina concentration (µg/ml) corresponding to MS: (H= 0.60 ± 0.22 µ/ml, R=0.65 ± 0.23 µ/ml, L= 0.60
± 0.29 µ/ml).
Conclusion: The results from the EMG and the RDC/TMD are consistent with a population of
asymptomatic subjects for TMD. From this classification we can accept the values of ME obtained as
normal and we use to compare with other populations of interest.
1112
CHANGES OVER TIME IN RELIABILITY OF PHYSICAL EFFORT DETERMINATION DURING
FUNCTIONAL CAPACITY EVALUATION IN PATIENTS WITH CHRONIC MUSCULOSKELETAL
PAIN
1,2
2,3
1
4
2
M. Trippolini , P.U. Dijkstra , B. Jansen , O. Peter , J.H.B. Geertzen , M.F. Reneman
1
2
2
Work Rehabilitation, Rehaklinik Bellikon, Bellikon, Switzerland, Department of Rehabilitation
3
Medicine, Center for Rehabilitation, Department of Oral and Maxillofacial Surgery, University Medical
4
Center Groningen, University of Groningen, Groningen, The Netherlands, Research Department and
Department of Rheumatology, Rehabilitation Centre Valens, Valens, Switzerland
Backgrounds and aims: To analyze the reliability of physical effort determination using observational
criteria during functional capacity evaluation (FCE).
Methods: Twenty-one raters assessed physical effort in 18 video-recorded FCE tests independently
on two occasions, 10 months apart. Physical effort was rated on a categorical four-point physical
effort determination (PED) scale, and a dichotomous submaximal effort determination (SED) scale
based on the Isernhagen criteria. Kappa values were calculated.
Results: Kappa values for the intra-rater reliability of the PED and SED scale for all FCE tests were
0.49 (95%CI: 0.22; 0.75) and 0.68 (95%CI: 0.60; 0.76) respectively. Kappa values for the inter-rater
reliability of the PED scale for all FCE tests in the first and the second session were 0.51 (95%CI:
0.23; 0.80), and 0.72 (95%CI; 0.49; 0.94), and for the SED scale Kappa values were 0.68 (95%CI:
0.60; 0.76) and 0.77 (95%CI: 0.70; 0.84) respectively. The inter-rater reliability of the PED scale
ranged from κ=0.02 to κ=0.99 between tests. Acceptable reliability scores (κ>0.60, agreement ≥80%)
for each FCE test were observed in 38% of scores for PED and 67% for SED. Averagely material
handling tests had a higher reliability than other tests.
Conclusion: Dichotomous ratings of submaximal effort are more reliable than categorical criteria to
determine physical effort in FCE tests. Education and training may improve the reliability of
observational criteria for effort determination.
1113
ISO 9001:2008 QUALITY CERTIFICATION OF A MULTIDISCIPLINARY PAIN PROGRAM
J.M. Munoz y Ramon
Unidad del Dolor - Pain Unit, Hospital Universitario La Paz, Madrid, Spain
Background: Pain Management constitutes an organisational challenge in all types of clinical
establishments. The ISO Norms can be an effective way of integrating the different components of a
comprehensive multidisciplinary programme. The experience in a large university hospital is shown
here.
Methods: A Multidisciplinary Pain Committee was created in a 1400-bed university hospital in Madrid
(Spain). 19 doctors from 17 specialties, 3 nurses, one pharmacist and one of the hospital directors
were integrated in six working groups with the objective of implementing the necessary steps leading
to the ISO Quality Certification of the organisation. A process map was designed, operating
procedures were developed and quality indicators were chosen. Manuals were written, policies for risk
management and data protection were outlined, and a critical incidents registry was created. Setting
up the process and completing the tasks took around one and a half years.
Results: After the effective implementation of all of the ISO recommendations, process management
became the regular methodology for work in the different areas integrated in the institutional pain
programme. A quality committee monitored both the compliance with the norms and the data derived
from the quality indicators. Once the committee was satisfied with the results, an accredited agency
(Bureau Veritas) for the external audit was chosen. The ISO Quality Certificate was awarded in March
2013.
Conclusions: ISO International Standards can be effectively applied to a Multidisciplinary Pain
programme in a tertiary care hospital. Process management can be a useful methodology for work
leading to efficiency, safety and quality.
1114
QUALITY ASSESSMENT, HETEROGENEITY AND PUBLICATION BIAS OF RESEARCH ON THE
PREVALENCE OF NEUROPATHIC PAIN
R.A. Elzahaf, O.A. Tashani, M.I. Johnson
Leeds Metropolitan University, Leeds, UK
Background: During the last decade investigating the prevalence of neuropathic pain (NeP) in the
general population became possible because of the availability of different measurement tools such
as DN4 and LANSS. The aim of this study was to retrieve surveys reporting the prevalence of NeP in
the general population and/or primary care and to assess quality, sources of heterogeneity and
publication bias.
Methods: Medline and other relevant databases were searched using the key words Neuropathic
Pain AND General Population OR Primary Care. Two reviewers, independently, assessed the
2
methodological quality of included survey. Forest plots were produced and the I test was used to
determine heterogeneity. Assessment of publication bias was performed using Egger´s test. All
analyses were performed using Comprehensive Meta-analysis Software.
Results: There were 182 hits of which 11 surveys from 10 countries met inclusion criteria (77313
people). All surveys scored ≥5/8 on quality assessment and used random sampling and all but one
used sample sizes >600. There was a low risk of publication bias (P< 0.378, Egger´s test) while
2
heterogeneity was large (I =99.028, P< 0.001) if fixed effect model was assumed.
Conclusion: The prevalence of neuropathic pain ranged from 3.3% to 17.9%. Studies estimating the
prevalence of neuropathic pain had a large amount of heterogeneity suggesting that any attempt to
pool this data should be interpreted with caution. The heterogeneity is likely to be due to differences in
survey methodologies, characteristics of target populations and the use of different tools to estimate
the prevalence of NeP.
1115
PAIN PREVALENCE IN NURSING HOME RESIDENTS: A SYSTEMATIC REVIEW
B.M. Fullen, A. Kitova
School of Public Health, Physiotherapy and Population Science, University College Dublin, Dublin,
Ireland
Background and aims: Up to 80% of residents in nursing homes experience significant levels of
1
pain . As numbers of elderly people increases worldwide, managing pain in these residents will be a
major consideration. The aim of this review is to establish the prevalence of pain in cognitively intact
patients in nursing homes.
Methods: The review comprised three phases: a methodological assessment of databases (PubMed,
CINAHL, Cochrane Central, PsychInfo, EMBASE and Pedro) identified papers which were screened
for inclusion criteria by two independent reviewers. Data were extracted from accepted papers, and
the internal validity of the papers was determined using a valid and reliable tool.
Results: Twelve studies (n=12) fulfilled all inclusion criteria, and the majority of studies were crosssectional in design. Pain prevalence rates in cognitively intact elderly ranged from 11-68.2% with an
average prevalence rate of 40%. Mean age of all participants was 81 years. Musculoskeletal pain
(spine and peripheral joints) was the most common category. Five of the papers were rated as high
quality, five as moderate quality, and two as low quality.
Discussion: Pain prevalence rates in cognitively intact nursing home residents are high, and needs
to be addressed. Consideration also needs to be given to standardising how prevalence rates are
established in such facilities to maximise patient care.
References:
1. Herr KA, Garand L. Assessment and measurement of pain in older adults. Clinics in Geriatric
Medicine 2001;17(3):575-594.
1116
OPIOID-INDUCED HYPERALGESIA AND TOLERANCE IN A PERIOPERATIVE SETTING: A
REVIEW
1
1
1
1
1
1
1
1
C. Flood , R. Fisher , D. Sarode , E. Bhatti , M. Durbacz , C. Ruddy , B. Collier , S. Smith , S.
2
Ramaswamy
1
2
MBChB Year 2, The University of Edinburgh, Edinburgh, Pain Clinic, Charing Cross Hospital,
London, UK
Background and aims: Opioid tolerance and Opioid-induced hyperalgesia (OIH) are two
phenomenons causing poor analgesic response to opioids. In this review we evaluated the evidence,
mechanisms, diagnosis and management of tolerance and OIH in an acute perioperative setting.
Methods: We did a search on Medline Ovid, Embase and Google scholar retrieving papers in English
language using appropriate keyword searches.
Results: Evidence and mechanism, the clinical evidence regarding tolerance in a perioperative
setting is mixed with some good quality studies supporting its existence. Animal studies suggest
involvement of NMDA, nitric oxide systems, and possibly dopaminergic neurones. In secondmessenger systems, protein kinase C receptors and phospholipase C may also be involved. We need
further research to look at the mechanisms in humans.
Evidence for OIH in perioperative setting is conflicting and scarce. Although the exact mechanism is
not yet understood, proposed mechanisms include spinal dynorphins or enhanced nociceptive
response. Most likely, it is related to the incorrect activation of NMDA receptors.
Diagnosis and management: Diagnosis of OIH and tolerance is difficult and they also can coexist.
Tolerance can be managed by increasing the opioid dose within therapeutic boundaries. Treatment
options for OIH include dose reduction, opioid rotation and use of specific adjuvants including NMDA
antagonists. Apart from using balanced analgesia, there is evidence to suggest that drugs like
ketamine, clonidine, buprenorpnine, methadone-d-isomer and naltrexone may be useful adjuvants.
Conclusion: There is a need for more human studies to look into the evidence, mechanisms and
management of tolerance and OIH in perioperative settings.
1117
DOES MAGNETIC RESONANCE IMAGING PREDICT FUTURE LOW BACK PAIN? A
SYSTEMATIC REVIEW
1
2
1
3
4,5
D. Steffens , M. Hancock , C.G. Maher , C. Williams , T.S. Jensen , J. Latimer
1
1
Musculoskeletal Division, The George Institute for Global Health, Sydney Medical School, The
2
University of Sydney, Discipline of Physiotherapy, Faculty of Human Sciences, Macquarie University,
3
4
Active Physiotherapy Newtown, Sydney, NSW, Australia, Research Department, The Spine Centre
5
of Southern Denmark, Middelfart, Institute of Regional Health Services Research, University of
Southern Denmark, Faculty of Health Sciences, Odense, Denmark
Purpose: Investigate whether magnetic resonance imaging (MRI) findings of the lumbar spine predict
future low back pain (LBP) in different samples with and without LBP.
Methods: We identified eligible studies searching MEDLINE, CINAHL and EMBASE databases up to
May 2012. Included were prospective cohort studies investigating the relationship between baseline
MRI abnormalities of the lumbar spine and clinically important LBP outcome at follow-up. We
excluded cohorts with specific diseases as the cause of their LBP. Data extraction and the
methodological quality assessment were completed by two independent reviewers. Associations
between MRI findings and LBP pain outcomes were extracted from eligible studies.
Results: The search identified 6666 potentially relevant articles. Of these, only 12 studies met the
inclusion criteria. Six studies presented data on participants with current LBP, one included a sample
with no current LBP, three included a sample with no history of LBP and 2 included mixed samples.
Due to the small sample size, poor overall quality and the heterogeneity between the studies in terms
of the participants, MRI findings and clinical outcomes investigated, it was not possible to pool
findings. Single studies reported significant associations for Modic Changes type 1 (OR=6.2,
95%CI=1.9-20.2) with pain, and disc degeneration with disability (OR=2.2, 95%CI=1.2-4.0) in samples
with current LBP, and disc herniation (OR=0.2, p=0.01) with pain in a mixed sample.
Conclusion: The limited number, heterogeneity and overall quality of the studies does not permit
definite conclusions on the association of MRI findings of the lumbar spine with future LBP.
1118
DEFINING CHRONIC PAIN IN EPIDEMIOLOGICAL STUDIES - A SYSTEMATIC REVIEW
1
2
Ó.A. Steingrímsdóttir , T. Landmark , C.S. Nielsen
1
1
2
Norwegian Institute of Public Health, Oslo, Norwegian University of Science and Technology,
Trondheim, Norway
Background and aims: To enhance the comparability of the prevalence estimates of chronic pain,
there is an obvious need to standardize the definition of the phenomenon. Our aim was to document
the different operational definitions of chronic pain and the resulting prevalence estimates in the
epidemiological literature.
Methods: Medline (1946 to 20 March 2013), EMBASE (1974 to 20 March 2013) and PSYCHINFO
(1967 to March week 2 2013) databases were searched for English language publications. The
search yielded a total of 3035 hits. Only original research reports with study samples of 1000
individuals or more were included. We excluded studies of regional pain (defined as information
limited to less than five body regions), and studies solely concerned with specialized pain conditions.
Preliminary findings resulted in 73 publications.
Results: The studies included estimates from countries of every continent. The data were gathered in
form of questionnaires, face-to-face interviews or telephone interviews. The principal findings were
huge inconsistency in the definition of chronic pain across studies and in the resulting prevalence
estimates (Figure 1). Hardly two studies accessed chronic pain in the exact same manner. Overall
prevalence estimates ranged from 9 to 64 percent, with a mean of 32 percent.
Conclusions: Lack of consistency in the definition of chronic pain make comparison of results from
different studies difficult and prevalence estimates uncertain.
[A forest plot]
1119
WHAT CAN WE LEARN FROM A META-ETHNOGRAPHY OF CHRONIC NON-MALIGNANT
MUSCULOSKELETAL PAIN?
1
2
3
4
5
1
F. Toye , K. Seers , N. Allcock , M. Briggs , E. Carr , J. Andrews , K. Barker
1
1,6
2
Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust, Royal College of Nursing
3
Research Institute, School of Health & Social Studies, University of Warwick, Oxford, School of
4
Health and Life Sciences, Glasgow Caledonian University, Glasgow, Institute of Health and Well
5
Being, Leeds Metropolitan University, Leeds, UK, Faculty of Nursing, University of Calgary, Calgary,
6
AB, Canada, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science,
University of Oxford, Oxford, UK
Background: Alleviation of pain is a key aim of healthcare yet chronic pain remains a challenge.
Qualitative research can enhance evidence based practice by increasing understanding. Our aim was
to systematically review and integrate the findings of qualitative research, and develop a model that
facilitates understanding of patients' experiences of chronic non-malignant MSK pain.
Method: Synthesis of qualitative research using meta-ethnography. Key concepts are identified,
compared across studies and organised into categories with shared meaning. A conceptual model is
developed. Data sources - Six electronic databases up to February 2012 (Medline, Embase, Cinahl,
Psychinfo, Amed and HMIC), supplemented by hand-searching contents list of specific journals and
citation tracking. Study Inclusion Criteria: published reports of qualitative studies exploring adults'
experience of chronic (3 months or more) non-malignant musculoskeletal pain.
Results: Included 77 papers reporting 60 individual studies. Fundamental to patients' experience is a
constant adversarial struggle:
(1) to affirm my-self;
(2) to re-construct self in time;
(3) to construct an explanation for suffering;
(4) to negotiate the healthcare system;
(5) to prove legitimacy. Our model suggests possibilities for (6) moving forward alongside pain
through: developing a more integrated body; regaining a positive sense of self; communicating pain;
knowing that I am not the only one; re-gaining a sense of reciprocity; recognising the limitations of the
medical model; being empowered to change.
Conclusion: Affirming a person's experience and allowing an empathetic interpretation of their story
is not an adjunct, but integral to health care. This has clear implications for clinical practice and
education.
1120
CAN MORPHOLOGY OR FUNCTION OF DEEP TRUNK MUSCLES PREDICT FUTURE CLINICAL
OUTCOMES IN NON-SPECIFIC LOW BACK PAIN? A SYSTEMATIC REVIEW
1
1
1,2
1
A.Y. Wong , G.N. Kawchuk , E.C. Parent , M. Funabashi , T.R. Stanton
1
3,4
2
Physical Therapy, University of Alberta, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada,
4
Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Neuroscience
Research Australia, Sydney, NSW, Australia
3
Background and aims: Prior investigations suggest a positive relation between muscle function and
low back pain (LBP). Specifically, the morphological/neuromuscular characteristics of transversus
abdominis or lumbar multifidus muscles may predict clinical LBP outcomes. Unfortunately, a related
systematic review is unavailable. The goal of this systematic review was to summarize evidence
regarding the predictive value of muscular function with respect to LBP outcomes.
Methods: Publications were identified from six electronic databases. Five cohort studies met
predefined inclusion criteria. Evidence synthesis was conducted based on risk of bias assessment
and consistency of findings.
Results: Limited evidence revealed that the baseline contraction thickness ratio and baseline
feedforward timing of transversus abdominis were not related to short- or long-term LBP intensity
following different exercise interventions. Nonetheless, limited evidence suggested that reduced
lateral sliding of transversus abdominis at baseline was associated with higher LBP intensity following
exercise interventions at 1-year follow-up. Interestingly, limited evidence showed that poor baseline
transversus abdominis contraction thickness ratio might positively modify treatment effects of motor
control exercise. There was conflicting evidence regarding a relation between baseline percent
thickness change of lumbar multifidus during contraction and the clinical outcomes of patients
following conservative treatments. No research investigated the relation between muscular
morphology at rest and clinical outcomes.
Conclusions: The results of this review suggest a very weak or no relation between the baseline
muscular function and future LBP outcomes. Given the small number of included studies, our results
should be interpreted with caution until large-scale prospective studies can be conducted.
1121
CAN CHANGES IN DEEP TRUNK MUSCLES PREDICT POST-TREATMENT CLINICAL
OUTCOMES IN NON-SPECIFIC LOW BACK PAIN? A SYSTEMATIC REVIEW
1
1
1,2
A.Y. Wong , G. Kawchuk , E.C. Parent , M. Funabashi
1
1
2
Physical Therapy, University of Alberta, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada
Background and aims: Some conservative treatments are thought to improve clinical outcomes in
persons with low back pain (LBP) by improving the activity of transversus abdominis and lumbar
multifidus muscles. This systematic review aims to summarize evidence regarding which posttreatment characteristics of these muscles may predict clinical improvement.
Methods: Publications were identified from six electronic databases. Two independent reviewers
selected articles according to predetermined selection criteria. Fifteen articles were included after
screening. Evidence synthesis was conducted based on risk of bias assessment and consistency of
findings.
Results: There was strong evidence that changes in transversus abdominis contraction thickness
were not related to changes in LBP or LBP-related disability. Further, there was moderate evidence
suggesting a lack of relation between feedforward timing of transversus abdominis and post-treatment
improvements in LBP or LBP-related disability. Limited evidence supported the absence of a relation
between changes in lateral sliding of transversus abdominis and changes in LBP. Conflicting
evidence was found for the relation between changes in multifidus contraction thickness and
improvements in post-treatment LBP-related disability. Similarly, conflicting evidence was noted for
the relation between changes in multifidus muscle endurance or morphology and post-treatment
improvements in LBP or LBP-related disability.
Conclusions: Overall, changes in transversus abdominis activity do not predict corresponding
improvements in LBP or LBP-related disability. The relation between changes in characteristics of
lumbar multifidus and post-treatment clinical improvements remains elusive. Future prospective
studies should investigate whether the relations between the changes in muscle function and clinical
outcomes are contingent on treatment types.
1122
“CAPS” - CARDIAC ACUTE PAIN SERVICES - A NATIONWIDE SURVEY
1
2
3
1
J. Cogan , N. Eipe , G. Vargas-Schaffer , S. Belisle , M.-F. Ouimette
1
4
2
Anesthesia, Institut de Cardiologie de Montréeal, Université de Montréal, Montréal, QC, Anesthesia,
3
Ottawa Hospital, University of Ottawa, Ottawa, ON, Anesthesia, Hotel Dieu, Université de Montréal,
4
Nursing, Institut de Cardiologie de Montréeal, Université de Montréal, Montréal, QC, Canada
Introduction: Acute Pain Services (APS) have been well established in Canada and their services
improve the management of postoperative pain. The availability and use of APS in cardiac surgery
units however is less widespread and even where present may be provided less consistently. We
undertook a nationwide survey to assess the current national situation.
Methods: The survey was approved by the IRB. A questionnaire was drafted by two
anesthesiologists working in pain management and reviewed for content validity by a domain
specialist. The twenty items that were retained covered structure, functioning and demographics of
the pain services. A list of all the national centers performing adult cardiac surgery was drafted and
the survey sent via “Survey Monkey.
Results: We received completed questionnaires from 30 of 32 centers and achieved a response rate
of 94%. Of the centers poled 57% had an acute pain service, 27% did not and 16% did not respond to
the question. Of those who answered the question 57% had been functioning for more than 5 years,
14% for 2 to 5 years and 28% for less than 2 years. In terms of functioning 15% were physician run
only, 31% had a dedicated pain nurse and the bulk had a hybrid form of APS. Most centres followed 5
or less patients per week.
Discussion: Acute pain services in cardiac care centers are varied in both structure and functioning
with nearly as many variations as there are sites. In general pain management is a protocol driven
activity.
1123
LOW BACK PAIN AND LOWER EXTREMITIES WEAKNESS AS INDICATIONS FOR
INTERVENTIONAL PAIN PROCEDURES
1
2
I. Melnytskyy , A. Alkhudari , M.L. Torres
2
1
2
Anesthesiology, John h Stroger Hospital, Naperville, Anesthesiology and Pain Management, John h
Stroger Hospital, Chicago, IL, USA
Background and aims: Low Back Pain (LBP) is 2
the world.
nd
reason for primary care physician office visits in
Methods: 45 y.o. pt with h/o LBP for 5 years due to T11-T12 and T12-L1 disk herniation presented to
the hospital with worsening of LBP and bilateral weakness in lower extremities (LEs). Patient denied
bowel/bladder incontinence upon admission. Motor strength 3/5 in thighs and calves and 5/5 in feet
bilaterally upon admission. Pain Service consult requested for possible lumbar epidural steroid
injection (LESI). Medical management started.
On day #7 patient developed severe weakness in LEs bilaterally.
MRI of lumbar spine (LS) revealed L5-S1 disc bulge, ligamentum flavum hypertrophy with mild right
and severe left neuroforamanial narrowing. On day #8 pain 8/10, muscle strength remained 2/5 in all
muscle groups. 2nd MRI of LS revealed ovoid lesion in left posterolateral aspect of spinal canal in L2L3 which may represent complicated synovial cyst from either L facet joint or from unusual migration
of disk extrusion. On day #9 L2-L3 laminectomy with decompression was performed w/o
complications.
Results: On postoperative day #5 pain well controlled with oral medications. Muscle strength in LEs:
4/5 hip flexions b/l ; 3/5 in rest of muscle groups.
Conclusions: Careful correlation of clinical and radiological findings is required when abnormal
neurological findings are detected.
Radiological investigations may detect abnormalities at multiple levels but cannot confirm which level
is primarily responsible for a patient's symptoms.
LESIs should be avoided if ethnology of weakness is unclear.
1124
EPIDURAL LABOUR ANALGESIA: MATERNAL SATISFACTION GUARANTEED?
A.C. Rocha, I. Duque
Anesthesiology, ULS de Castelo Branco, EPE, Castelo Branco, Portugal
Background and aims: Maternal satisfaction has become a way of assessing and improving quality
1,2
of obstetric units . The purpose of this study was to assess the knowledge and satisfaction among
pregnant women after epidural analgesia (EA).
Methods: Satisfaction was assessed by a standardized questionnaire conducted by telephone after
verbal consent. One hundred and thirty-two patients who received EA over a one-year period in the
Hospital Amato Lusitano, Castelo Branco, were asked to participate. The authors enquired different
aspects of EA: availability of antenatal information, women's decision to use the technique, fears and
expectations, analgesia for future deliveries and overall maternal satisfaction.
Results: 110 questionnaires were retrieved (83.3% of the women). The mean (± SD) age was 29±5.4
years. Maternity classes were the primary source of information on labour analgesia (47% not
mutually exclusive answers). 50 women (45.5%) planned to receive EA and the remaining hoped to
avoid it (painful labour was the main reason for request). Of the 110 respondents, 109 (99%)
considered EA safe for them and for the baby, 97 (88.2%) found lateral position comfortable and 100
(90.9%) referred no pain during epidural placement. The overall maternal satisfaction using a Likert
scale of 5 points was 4.4±0.7 (minimum = 1, maximum = 5).
Conclusions: Although patient satisfaction with EA was significantly higher, the majority hoped to
avoid it. Lack of antenatal information and cultural background may justify this ante-partum decision.
Future studies should be developed in our institution after further efforts for promoting epidural use.
1125
MULTICENTER ANALYSIS OF PAIN CONTROL EFFICACY. DIFFERENCES IN THE USE OF
ADVANCED ANALGESIC TECHNIQUES
E. Schiappa, C. Compagnone, A. Markidis, M. Berti, G. Fanelli
2° Servizio Anestesia, Rianimazione e Terapia Antalgica, on behalf of ReMIDA Study Group, A. O.
Ospedaliero - Universitaria Parma, Parma, Italy
Background and aims: From 30 to 80% of patients complain post-surgical pain from moderate to
severe, indicating that the treatment of post-operative pain is still a problem. The aim of this study is to
analyze the efficacy of post-operative analgesia in the patients undergoing general surgery followed
by the Acute Pain Service (APS) in different centers.
Method: We analyzed prospectively collected data from patients followed by APS after general
surgery from January to December 2012 in 5 Centers. We evaluated the presence of pain, pain
intensity, and post-operative analgesia: epidural patient-controlled analgesia (PCA and EPCA),
continuous peripheral nerve block (CPNB), others.
Results: 781 patients were included in the analysis. The principal types of surgery were: Bowel
surgery (bowel resection 153(23.1%), Hemicolectomy 107(16.2%)), Gastrectomy 100(15.21%) and
Cholecystectomy 97(14.6%). 383 (49.4%) experienced pain equal to NRS> 4, distributed as follow:
Center 1 42.5%, Center 2 38.4%, Center 3 49.1 %, Center 4 24.1 % and center 5 77.9% of treated
patients (p< 0.005). Center 1 presented a used of advanced technique in (67.9 %) and Center 5 only
in 25% (p = 0.0005), without a significant difference in kind of surgery.
Conclusions: The uses of non advanced analgesic techniques are still wide extended. Not only for
their simplicity but also because they required a lower level of resources. However, the use of the
advanced techniques of post-operative analgesia reduces the incidence of moderate/severe pain.
Continuous education of sanitary personal may improve the control of post-operative pain.
1126
EXPERIENCES OF A REQUIRED E-LEARNING TRAINING ABOUT PAIN FOR ALL NURSES IN A
UNIVERSITY HOSPITAL: WHY AND HOW
1
2
1
2
Y. Bangala-Kottelat , S. Gallant , I. Décosterd , M. Roessli
1
2
Anesthesiology, Pain Center, Continuing Education Center, Centre Hospitalier Universitaire Vaudois
(CHUV), Lausanne, Switzerland
Background and aims: Since 2009, an institutional pain program is implemented in the CHUV, a
tertiary university hospital in Lausanne, Switzerland.
Continuing education in pain management is an important way to increase gain knowledge, and
therefore, modify and improve the caregivers' clinical practice. To train nursing staff, a pilot e-learning
program on pain management was tested 2 years ago. Today, it is required that all nurses complete
the training.
Methods: Training consists of numerous themes. Each is composed of 6-10 audio commented slides
and lasts about 5 minutes. It is available on an internet e-learning platform requiring a password to
access.
In order to test gain knowledge, trainees are requested to fill in an identical quiz before and after
viewing each topic, as well as a random selection of 2/3 of all the quiz questions.
Participation is mandatory and organized with the chief nurses. Training takes place either during a
specific dedicated training time in a teaching room equipped with 18 computers, or to the convenience
of the staff during worktime or personal time. Extra time might be allowed.
Results: Before-after quiz scores are the indicator chosen to demonstrate the training impact.
Passing score is fixed at 70% good results.
Results will be presented.
Conclusion: This model of training is particularly relevant when the goal is sensitization to pain
management. Workshops will be organized to deepen failed topics.
Topics can be tailored to target audience and units needs.
One could imagine that every nurse should re-validate it each year.
1127
SURVEY ON AWARENESS OF ABDOMINAL CUTANEOUS NERVE ENTRAPMENT SYNDROME
(ACNES) AMONGST SURGEONS
S.S. Bhayani, A.J. Ravenscroft
Pain Management Unit, Nottingham City Hospital, Nottingham, UK
Background and aims: Abdominal Cutaneous Nerve Entrapment (ACNES) is a common source of of
chronic abdominal pain. Failure to recognise ACNES can lead to unnecesary investigations and
1
2.
surgery with financial and resource implications.
We aimed to evaluate the knowledge and
awareness of this condition amongst surgeons.
Methods: We invited 70 local surgeons to complete an online survey.
Results:
Grade
Total
Consultant
ST3 or above
Responses
44
25
19
Have you heard of
ACNES?
16 Yes
12 Yes
4 Yes
Have you heard of
Carnett's Syndrome?
5
5 Yes
0
1 Yes
0
Have you read about
ACNES in your surgical 1 Yes
books?
[Results of the survey- Awareness of ACNES]
Of those familiar with ACNES 15/16 said they would confirm the diagnosis using clinical examination,
with injections of local anaesthetic into the abdominal wall for confirmation. ConclusionThe results
demonstrate that many of our local surgeons, in particular the trainees are unfamiliar with the
condition ACNES. This is surprising given its prevalence amongst patients presenting to surgical
3
outpatients.
There is a need for better education of surgeons regarding ACNES. This should be done by including
this condition in surgical curriculum and text books.
Disclosure: None to declare.
References:
1. Applegate WV. Abdominal cutaneous nerve entrapment syndrome(ACNES) a commonly
overlooked cause of abdominal pain Perman J.2002;6: 20-272.
2. Thompson C, Goodman R, Rowe WA. Abdominal wall syndrome: a costly diagnosis of exclusion.
Gastroenterology. 2001;120(suppl 1):A637.
3. J Pak Med Assoc. 2012 Mar;62(3 Suppl 2):S17-20. Chronic abdominal wall pain: prevalence in outpatients. Adibi P, Toghiani.
1128
THE PROVISION OF PAIN EDUCATION WITHIN UNDERGRADUATE MEDICAL STUDIES
ACROSS EUROPE
1
2
3
4
5
6
H.G. Kress , D. Battelli , E. Briggs , D. Gordon , A. Kopf , S. Ribeiro , M. Puig
7
1
Dept of Special Anaesthesia and Pain Therapy, Medical University of Vienna/AKH, Vienna, Austria,
Dept of Anesthesia and Intensive Care, University of Modena e Reggio Emilia, Modena, Italy,
3
4
Florence Nightingale School of Nursing & Midwifery, King's College London, London, UK, Faculty of
5
Health Sciences, University of Copenhagen, Copenhagen, Denmark, Pain Clinic, Charité Medical
6
7
University, Berlin, Germany, Primary Healthcare Cluster of Sintra, Sintra, Portugal, Dept of
Anaesthesiology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain
2
Aims: Inadequacies in undergraduate pain medicine education are a potential barrier to
improvements in pain management. This initiative aims to promote the inclusion of pain medicine as a
compulsory topic on undergraduate medical curricula and to raise awareness of the importance of
pain education in Europe. This initial research will benchmark current levels of pain education within
undergraduate medical courses.
Methods: Phase 1 was a detailed quantitative review of pain education targeting all medical schools
across 15 representative European countries and using pain course curricula plus information on the
school and the organisation, topics, quantity and teaching/assessment methods of pain education.
Informed by Phase 1, the qualitative Phase 2 involves semi-structured, in-depth telephone interviews
with decision-makers (medical school deans/deputy directors and course leaders) and final-year
undergraduate students in up to 10 representative medical schools in each of 10 countries. The
decision-maker interviews will: validate and extend the quantitative research, and elucidate teaching
strategies, perceptions of pain education, potential barriers to its improvement, prioritisation, and
relevant decision-making and review processes. The undergraduate interviews will assess satisfaction
levels and perceived quality of pain education, its impact on confidence and knowledge, the
prioritisation of pain education, and the interest in pain specialisation. Institutional ethical approval will
be gained, as appropriate.
Results: Final results, expected Sept 2013, will be presented.
Conclusions: This unique project should provide a foundation for pan-European and national actions
to improve undergraduate pain medicine education.
Acknowledgement: Mundipharma International Limited is providing financial, logistical and editorial
support to this initiative.
1129
UNDERGRADUATE PAIN CURRICULA FOR HEALTHCARE PROFESSIONALS IN THE UNITED
KINGDOM: CHALLENGES AND SUCCESSES
1
2
3
4
5
E. Carr , E. Briggs , M. Briggs , N. Allcock , D. Jones , P. Black
1
6
2
Faculty of Nursing, University of Calgary, Calgary, AB, Canada, Florence Nightingale School of
3
Nursing & Midwifery, King's College London, London, Institute of Health & Wellbeing (Faculty of
4
Health and Social Sciences), Leeds Metropolitan University, Leeds, School of Health and Life
5
Sciences, Glasgow Caledonian University, Glasgow, Public Health & Wellbeing, University of
6
Northumbria, Newcastle upon Tyne, School of Nursing, University of Ulster, Londonderry, UK
Background and aims: The management of pain is generally agreed to be suboptimal across
hospital and community settings. One frequently cited reason is inadequate undergraduate pain
education for health professions. Many studies have highlighted inadequacies but few give insight into
factors that facilitate the provision of pain education. This study elucidated both challenges and
evidence of positive developments in pain education across undergraduate health professions'
programmes in the UK.
Methods: From the UK survey of pain content across 108 undergraduate programmes (Briggs et al.,
2011) the open text box for 'further comments' was analyzed (58 responses; 4,622 words). Analysis,
using NVivo 10 software for data management, was undertaken to inductively identify codes, which
were collapsed into themes.
Results: Contributions were received from 7 disciplines: Dentistry (2), Medicine (6), Midwifery (5),
Nursing (28), Pharmacy (2), Physiotherapy (9), and Occupational Therapy (6). Thematic analysis
revealed two major themes of challenges and successes, each with sub-themes. The theme of
challenges incorporates four sub-themes: inability to identify where pain is taught in the curriculum;
biomedical vs biopsychosocial approaches to pain and perceived importance; resources (time and
staff knowledge); and finally a diffusion of responsibility. In contrast the theme 'successes'
incorporates three sub-themes; providing evidence of positive developments: expansion of pain
education; multi-dimensional curriculum content; and diversity of teaching methods.
Conclusions: These findings provide insight and an understanding of ways to promote the inclusion
of pain education in undergraduate curricula.
Briggs, E. Carr, ECJ., Whittaker, M. (2011), Eur J P 15(8), 789-795.
1130
EDUCATIONAL APPROACH: INTRAMUSCULAR APPLICATION OF NSAIDS IN
MUSCULOSKELETAL PAIN - LEGE ARTIS OR MALPRACTICE?
1,2
N. Müller
1
2
Orthopaedic Practice, Zirndorf, Dept. Pharmacology, Friedrich-Alexander University ErlangenNürnberg, Erlangen, Germany
Background and aims: Not one of 25 consecutive patients in my orthopedic practice with a previous
NSAID “pain shot” reported hints for a medical reason for the injection pathway. Two questions
evolved: Estimation of the number of NSAID ampullas consumed. Test of the hypothesis that new
knowledge might prove significant advantages of parenteral NSAID.
Methods: Diclofenac prescriptions annually (the NSAID most widely used in Bavaria, 12x10e6
inhabitants, 95% covered by public health insurance) were obtained from “Kassenärztliche
Vereinigung Bayern” and evaluated. Literature was reviewed regarding clinical pharmacology and
legal matters of therapeutic and adverse effects of Diclofenac.
Results: Bavarians receive approx. 750000 Diclofenac injections per year. Rational reasons for this
remarkable amount could not be identified. Regarding the ratio of DDD given i.m. versus enteral DDD
there are considerable differences between medical professional groups. There is no superiority of
Diclofenac i.m. concerning efficacy. An overall risk ratio of 1:10 000 (low end of range) of severe ADE
linked to i.m. NSAID (anaphylaxis, necrosis, gangrene, fasciitis necrotisans, Nicolau-syndrome) may
cause 75 severe cases at least per year in Bavaria. Only medical reasons, but not the patient´s will,
can minimize legal consequences for health professionals in case of iatrogenic damage.
Conclusions: Numerous patients in Bavaria receive i.m. NSAIDs, in negligence of many
recommendations not to do so. An educational approach in the orthopedic professional group was
started. A follow-up is on the way. Relying on personal communications, we suspect that misuse of
NSAIDs i.m. may occur in other European regions, too.
1131
PAIN MANAGEMENT AWARENESS AMONG PRIMARY HEALTH CARE PHYSICIANS
1
2
N. Ninashvili , M. Shavdia , N. Shavdia
1
2
3
3
Tbilisi State Medical University, Palliative Care Clinic Cancer Prevention Center, Georgian
University, Tbilisi, Georgia
Background: In 2004, 54.7% of oncological patients were diagnosed with incurable (IV) stage of
cancer. Since then, the situation has not changed that resulted in the increasing trend of both primary and secondary oncoincurable patients. Symptom study of 538 patients showed, pain to be the
dominated complain (78.5%), prevalence of which ranged between 60.9% - 85.3% by ECOG WHO,
depending upon cancer stage (I-IV). It was critical to determine pain management tactics in primary
health care settings.
Methods: Descriptive epidemiological study was conducted in primary health care facilities - family
doctor centers in the capital city. Special questionnaire was developed and disseminated to 98 family
physicians, selected randomly in 5 centers throughout the city.
Results: Study showed that 91.8% of physicians didn't know half-life release of particular opioids;
50.0% was unaware of WHO Pain Relief Ladder for Cancer Pain; None of them used pain
assessment tools in practice; 89.8% prescribed opioids without identification of causative factors of
pain that led to inadequate pain management; 95.9% didn't know about opioid rotation, dosage and
routs of administration; 53.1% revealed inadequate knowledge of adverse effects as well as
management of opioids. The vast majority of study participants hadn't been trained in pain
assessment and management practice.
Conclusion: Increasing number of oncological patients, especially at cancer incurable stage requires
not only adequate palliative care but relevant pain management at any level of medical care. Study
results indicated urgent need for working out educational programs on pain management for
physicians of all specialties.
1132
THE PHARMACIST AND PAIN
J. Leclerc, L. Douay, P. Trenel
CHU Amiens-Picardie, Amiens, France
Background and aims: In France, the management of pain is registered in the public health code.
The pain seems now recognized and supported by all. What is it in pharmacies in town?
Methods: We conducted a mail survey of assessment practices for the management of pain in
pharmacies. The questionnaire consists of 10 items.
Results: 50 pharmacies have received the survey, 40 agreed to answer (80%).
We collected 105 responses, which are divided into 48 pharmacists and 57 processors.
88.3% believe that acute pain is a common reason for seeking advice, and 70.2% in chronic pain.
100% responded that the assessment is mandatory in the dispensary. 55% of pharmacists and 33.2%
preparers know the specifics of assessment in children. 70% of pharmacists know Visual Analogic
Scale, other assessment tools are rarely known. Pharmacies don´t have these tools. 100% seek the
origin of the pain before issuing an analgesic. Pharmacists and preparers are seeking training on the
pathophysiology and assessment. The pharmacist prioritizes treatment, education, in third position
evaluation.
Conclusions: The new reform of the hospital and relative to the patients,the health and the territories
(HPST) develops missions pharmacist: health first use, screening, patient education, monitoring
personalized treatments.
Pharmacist and preparer are essential links in the chain of management of pain. But we find it difficult
because of the lack of knowledge of assessment tools and their uses, as well as the orientation of
chronic pain patient to specialized structures.
Pharmacists should be an integral part of the pain network.
1133
CONSENT FOR REGIONAL NERVE BLOCKS: ROOM FOR IMPROVEMENT?
1
2
2
M.R.D. Brown , M. Henley , A. Pathmanathan , R. Zarnegar
1
1
2
Department of Pain Medicine, Department of Anaesthetics, Royal National Orthopaedic Hospital,
Stanmore, UK
Background and aims: In Britain consent for surgery is documented using a Department of Health
form signed by the surgeon and the patient. In contrast, regional techniques have no formalised
consent process. Discussions with patients are recorded, but there are no clear standards.
We aimed to determine patients' recall of consent for interscalene brachial plexus block (ISB) and
perceptions of this compared to surgical consent for shoulder arthroplasty.
Methods: We undertook a post-operative questionnaire survey on patients undergoing shoulder
arthroplasty. Recall of risk discussions was specifically questioned. Differences between recall and
non-recall groups were analysed using 2-tailed Fisher's exact test.
Results: All 22 (male:female 6:16, mean age 71 years) patients surveyed had a documented risk
benefit discussion regarding ISB. All recalled having a pre-operative discussion with the surgeon and
21 with the anaesthetist. Five (22%) did not recognise their discussion about ISB as part of the
consent process. In those who did, four (22%) did not consider it as important as surgical consent.
Surgery
ISB
P Value
Recall of risk
discussion happening
20
13
0.030
Recall of two actual
risks
12
4
0.026
[Table 1]
In the 15 patients who remembered reading the surgical consent form, fewer reported no recall of
surgical risks (p=0.013).
Conclusions: Recall of risks of nerve blocks is poorer than recall of surgical risk. Patients who
remember reading the consent form have better recall of surgical risks. Our results support the
introduction of written consent for regional blocks.
136
SATELLITE GLIAL CELL ACTIVATION OCCURS IN THE COLLAGENASE MODEL OF
OSTEOARTHRITIS IN RATS
1,2
1,2
1,2
1,2
1,2
1,2
S. Adães , J. Ferreira-Gomes , M. Mendonça , T. Santos , J.M. Castro-Lopes , F.L. Neto
1
2
Department of Experimental Biology, Faculty of Medicine of University of Porto, Institute of
Molecular and Cell Biology, Porto, Portugal
Background and aims: Pain is a major feature of osteoarthritis (OA), but its therapy is still highly
ineffective. Recently, the overexpression of glial fibrillary acidic protein (GFAP), a known marker of
satellite glial cell (SGC) activation, has been reported in several animal models of pain. Here, we
evaluated if this is also observed in the dorsal root ganglia (DRG) of rats with OA induced by intraarticular injection of collagenase, hoping to contribute to a better understanding of the pain
mechanisms in this pathology.
Methods: OA was induced by double injection of 500U of type II collagenase into the knee joint of
rats, at days 0 and 3. Movement-induced nociception was evaluated weekly, until sacrifice, by the
Knee-Bend and CatWalk tests. Animals were sacrificed 6 weeks after the first collagenase injection
(n=6/group). L3-L5 DRGs were used for immunodetection of GFAP, and knee joints were processed
for histopathological evaluation.
Results: Collagenase injected into the knee joint induced an increase in movement-induced
nociception when evaluated by both the Knee-Bend and Catwalk tests. Histopathological changes
observed after 6 weeks of OA induction were very similar to those described in clinical OA, leading to
extensive cartilage degeneration with fissures and exposure of the subchondral bone. GFAP
expression in the SGC of collagenase-injected animals was significantly increased when compared to
control animals.
Conclusion: The intra-articular injection of collagenase leads to SGC activation, which may be
implicated in the development of chronic pain in this model.
Granted by: a Calouste Gulbenkian Foundation PhD scholarship and FCT (PTDC/SAUNSC/119986/2010).
137
ASSOCIATION OF SYNOVIAL NERVE REGENERATION AND PAIN IN KNEE JOINT
OSTEOARTHRITIS
1
2
2
3
A.S. Ahmed , H. Nawaz , M. Umer , M. Ahmed
1
2
Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, Department of Surgery, Agha Khan
3
University, Karachi, Pakistan, Department of Neurobiology, Care Sciences and Society, Karolinska
Institute, Stockholm, Sweden
Introduction: Knee osteoarthritis (OA) is a most prevalent chronic painful joint disease. The role of
sensory and autonomic neuropeptide has been implicated in the pathogenesis of osteoarthritis (OA).
Little is known about the effects of nerve regenerating on pain and inflammation in OA. The aim is to
study the correlation between synovial nerve regeneration with pain and inflammation in OA patients.
Methods: Synovial biopsies were harvested from the medial, lateral and suprapatellar compartments
of knee joints from 13 patients undergoing joint replacement surgery. The clinical outcome of pain and
knee joint function was evaluated by knee society score and synovial inflammation was analyzed by
histology. Semi-quantitative analysis of synovial nerves containing sensory (SP, CGRP) and
autonomic (NPY, VIP, TH) neuropeptides and growth associated protein-43 (GAP-43) was performed
in synovium by using single and double immunohistochemistry techniques.
Result: Clinical evaluations indicated pain predominantly in the medial compartment of knee joint in
all patients. Histological analysis demonstrated severe inflammatory changes in the medial and
suprapatellar compartments compare to lateral in OA knee. A 70% increase in the GAP-43 and 80%
increase in the SP and CGRP and 50% increase in the TH were observed in the medial compared to
lateral compartment. Double staining analysis showed co-expression of GAP-43 with SP and CGRP
in the in the medial compartment.
Conclusion: There is an association of regenerating nerve fibers containing sensory and autonomic
neuropeptides with pain and inflammation in knee OA. Pharmacological tools targeting neuropeptides
may ameliorate pain in osteoarthritis.
138
NON-TRAUMATIC ARM, NECK AND SHOULDER COMPLAINTS: PREVALENCE, COURSE AND
PROGNOSIS IN A DUTCH UNIVERSITY POPULATION
V.E.J. Bruls, C.H.G. Bastiaenen, R.A. de Bie
Epidemiology, Center for Evidence Based Physiotherapy, Maastricht University, Maastricht, The
Netherlands
Background and aims: Complaints of arm, neck and shoulder (CANS) are a major health problem in
Western societies. Research data suggest that these complaints are increasingly common among
university students. Studies estimating the prevalence of these complaints among university students
are scarce.
The study aims are to provide insight into prevalence, clinical course and prognostic factors of CANS
in a university population.
Methods: The study design is a prospective cohort study, in which a cross-sectional survey is
embedded. A self-administered survey will be conducted among university staff and students, to gain
insight into the prevalence of CANS, and to identify persons who are eligible for follow-up in the
prognostic cohort study.
Persons with a new complaint of pain/ discomfort in neck or upper extremities between 18-65 years
are eligible for the cohort. At baseline, after 6,12, 26 and 52 weeks data will be collected by digitized
self-administered questionnaires. The following prognostic determinants will be investigated: socialdemographic, psychosocial and work-related factors, complaint characteristics and physical activity.
The primary outcome is subjective recovery. Secondary outcomes are functional limitations and
complaint severity.
Results: The baseline results regarding the prevalence of CANS among students and the baseline
characteristics of participants, are expected to be available in October 2013 and can be presented on
the congress of EFIC.
Conclusions: To our knowledge, this is the first prognostic study on the course of CANS in a
university population. The results of this study can be used for patient education, management
decisions and development of interventions.
139
EXPERIMENTAL NECK MUSCLE PAIN REORGANISES THE AXIOSCAPULAR MUSCLE
ACTIVITY DURING ARM MOVEMENTS
S.W. Christensen, R.P. Hirata, T. Graven-Nielsen
Laboratory for Musculoskeletal Pain and Motor Control, Center for Sensory-Motor Interaction (SMI),
Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
Background and aims: Clinical neck pain affects motor control of neck muscles as well as neck
function. So far the interaction between neck pain and motor function of the axioscapular muscles
(AM) is unclear. This study investigated effects of experimental neck pain on AM activity during arm
movements.
Methods: Twenty-four healthy volunteers (12 females) participated in this study. Muscle pain was
induced by injecting hypertonic saline into m. splenius capitis. Injection side was randomised. Isotonic
saline was injected as control on the contralateral side. Pain intensity was assessed on an electronic
visual analogue scale (VAS). Before, during and after injections the muscle activity was recorded
during repeated and controlled movements (30° to the frontal plane). Electromyography (EMG) was
measured over eight muscles bilaterally and the root-mean-square values extracted as a measure of
the muscle activity.
Results: VAS scores were higher after hypertonic saline compared with isotonic saline (P< 0.01).
During “up” movements, the EMG amplitude decreased in upper trapezius (P< 0.01) while middle
deltoid muscle showed an increased amplitude (P< 0.03) during pain compared with baseline and the
control injection. For “down” movements, the upper trapezius muscle showed decreased activity
during the painful condition (P< 0.01) while the contralateral external oblique muscle showed an
increased activity (P< 0.03).
Conclusions: These results showed that experimental neck pain in a muscle not functionally
connected with arm movement caused alterations in the AM function. The reorganised distribution of
muscle activity may cause overloading of other structures otherwise not implicated in the neck pain.
140
TRIGGER POINTS INJECTIONS IN MYOFASCIAL PAIN SYNDROME AND FIBROMYLAGIA: ARE
WE SERVING OUR PATIENTS WELL?
1
1
2
A. Clairoux , G. Vargas-Schaffer , J. Cogan
1
Pain Center, Centre Hospitalier de l'Université de Montréal (CHUM), Hôtel-Dieu, Université de
2
Montréal, Department of Anesthesia, Montreal Heart Institute, Université de Montréal, Montreal, QC,
Canada
Background and aims: Myofascial syndrome is a disorder characterized by the presence of
myofascial trigger points (MTrPs) which result in a symptomatic pain response. After failure to
respond to first line treatments, trigger point injections are suggested for active trigger points.
However, some authors contest their efficacy. The objective of this study was to quantify the pain
relief provided by MTrPs injections.
Methods: This ethics approved retrospective descriptive study reports on 85 patients attending a
st
th
tertiary care pain center between October 1 2011 and February 29 2012. The following data was
collected: primary diagnosis, MTrPs localisation, MTrPs injection frequency, local anesthetics and
steroids used, other treatment modalities, pain relief as measured with the Visual Analog Scale (VAS),
duration of pain relief and complications, if any.
Results: Of the 85 patients 70 had a diagnosis of myofascial pain syndrome, 14 of fibromyalgia and 1
of failed back surgery syndrome. Most MTrPs injections were in the trapezius muscles (23.8%),
paravertebral lumbar (20.8%) and paravertebral cervical (12.7%) muscles. All injections were done
with at least one local anesthetic (bupivacaine and/or lidocaine) and with or without triamcinolone.
Mean VAS scores decreased from 7.68 pre MTrPs injection to 3.68 post injection. The pain relief
during maximal effect, as reported by patients, lasted for a mean of 6 weeks; 6.8 weeks with
triamcinolone and 4 weeks without.
Conclusion: This study shows that MTrPs injections are effective in decreasing pain. Additionally, the
use of triamcinolone provides improved and longer pain relief than local anesthetic alone.
141
CHARACTERISATION OF THE PERIPHERAL NEURONAL PHENOTYPE OF PAINFUL ROTATOR
CUFF TENDINOPATHY
S.L. Franklin, B.J.F. Dean, A.J. Carr
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford
University, Oxford, UK
Background and aims: Shoulder pain is the third most frequent cause of chronic musculoskeletal
pain in the community and is usually caused by rotator cuff tendinopathy (RCT). The central and
peripheral nervous system play an important role in both tissue homoeostasis and tendon healing.
The Glutaminergic system is of key importance in driving the peripheral and central pain pathways.
We hypothesised that the peripheral neuronal phenotype would be altered in RCT, and would vary
according to disease stage as measured by size of tear.
Methods: Rotator cuff supraspinatus tendon specimens were obtained from 64 patients undergoing
the surgical repair of rotator cuff tears. Healthy supraspinatus tendon was used as a control. The
tendon tissue was immunohistochemically stained with primary antibodies visualised using 3,3'diaminobenzidine (DAB). Quantification of DAB positive staining was carried out.
Results: The Glutaminergic system was significantly up-regulated with an increase in Glutamate and
changes in several related receptors in disease versus control (p< 0.01). The standard deviation in
nuclei count and mean cell nuclear area were both increased in disease (p< 0.01) compared to
controls. Tendon vascularity and cell proliferation were reduced in disease vs control (p< 0.01). There
were no significant correlations between pain scores and the peripheral tissue markers.
Discussion: The peripheral neuronal phenotype is significantly altered in rotator cuff tendinopathy
with clear changes in the Glutaminergic system in disease. These findings are novel and further our
understanding of the disease process in RCT, and these targets could be used in the development of
novel therapeutics.
142
CHANGES IN THE PERIPHERAL NERVOUS SYSTEM AFTER REPAIR OF THE HUMAN
ROTATOR CUFF
S.L. Franklin, B.J. Dean, R.J. Murphy, K. Wheway, B. Watkins, A.J. Carr
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford
University, Oxford, UK
Background and aims: Painfully symptomatic tears in shoulder tendons are frequently repaired
surgically by rotator cuff repair, however little is understood how surgery may affect the repairing
tissue. Central and peripheral nervous system pathways play an important role in tissue homoeostasis
and tendon healing. This is the first study to date to describe peripheral nociceptive changes
occurring after rotator cuff repair in humans.
Methods: Paired rotator cuff supraspinatus tendon specimens were obtained from patients
undergoing rotator cuff repair using a novel ultrasound guided biopsy technique; biopsies were taken
at time of surgery and 7 weeks post-operatively. Tissue was stained using Haematoxylin and Eosin,
and with primary antibodies visualised using 3,3-diaminobenzidine (DAB). Image analysis was
performed and the amount of DAB positive staining quantified. Significance levels were set at p< 0.05.
Results: Tendon vascularity and cellularity were significantly increased 7 weeks post operatively. The
Glutaminergic system was significantly up-regulated at 7 weeks with an increase in Glutamate
(p=0.0195) and changes in several related receptors (p< 0.05). The nerve marker PGP9.5 was
significantly increased at seven weeks (p=0.01). There were no significant correlations between pain
scores and the peripheral tissue markers.
Conclusion: RCR results in significant tissue changes which involve the Glutaminergic system.
These findings are novel and improve our understanding of tissue healing in rotator cuff tendinopathy,
and potentially provide novel therapeutic targets.
143
ASSOCIATION BETWEEN PAIN LEVEL AND TYPE OF TREATMENT OPTIONS AFTER PILON
FRACTURES
F. Haxholli, V. Hysenaj, M. Haxholli, V. Bllaca
University Clinical Center of Kosovo, Prishtina, Kosovo
Introduction: The distal tibial fractures that includes ancle joint (pilon fractures) are severe,
associated with soft tissue damage and ranges from minimal to maximal displacement of fragments.
Aim: To assess pain levels after application of physical therapy in surgically treated patients in
association with the conservatively treated group.
Material and methods: Hospitalized and treated patients (n=36) were studied in prospective mode in
Orthopedic and Traumatologic Clinic in Pristina from January 2010 to December 2012. Studied
patients were of different age, gender, professions and places. To estimate the degree of
rehabilitation three comparative groups are formed based on Visual Analogue Scale.
Results: The intensity of pain after application of physical therapy in operatively treated patients has
resulted as follows: mild cases, no or minimal pain (0-3) were 15 cases or 48%, moderate cases, with
pain in straining (4-7) 9 cases or 29% and with severe pain (8-10) 7 cases or 22.6%. Among
conservatively treated patients: no or minimal pain were 0 cases, with moderate pain 1 case or 3.2%
and severe pain 4 cases or 12.9%.
Conclusion: Although pilon fractures are one of the most severe bone injuries, careful assessment
and the right time for operative intervention are crucial for success. By respecting these principles and
early start of Physical Therapy, the results are promising.
144
INCREASED AEROBIC CAPACITY IS IMPORTANT IN RELIEVING KNEE PAIN IN OBESE
INDIVIDUALS
1,2
1
1,2
3
T. Ikemoto , T. Hasegawa , T. Ushida , E. Shibata , F. Kobayashi
1
3
2
Institute of Physical Fitness, Sports Medicine and Rehabilitation, Multidisciplinary Pain Center,
Department of Health and Psychosocial Medicine, Aichi Medical University, Nagakute, Japan
3
Objective: The aim of this study was to investigate the features of overweight or obese individuals
2
with a BMI ³25 kg/m who complained of low back pain, knee pain, and shoulder stiffness.
Design and methods: The subjects comprised 88 obese individuals who were first divided into a
symptomatic group and an asymptomatic group prior to the weight-loss intervention in order to
compare several parameters of each group. Symptomatic patients were furthermore divided into
groups of subjects whose symptoms did or did not improve as a result of the 6-month weight-loss
intervention. Changes in the test parameters from before and after the intervention were compared
between the two groups.
Results: The results revealed no differences in any parameters between the two groups
(symptomatic and asymptomatic) at baseline in shoulder stiffness or low back pain. However, for knee
pain, the VO2max was significantly lower in the symptomatic group than in the asymptomatic group
(P< 0.05). Furthermore, the weight-loss intervention revealed a significant increase in VO 2max in the
“improved” group compared to the “no change” group (P< 0.05).
Conclusion: The study results showed that both weight loss and the acquisition of aerobic capacity
were important in relieving knee pain in obese individuals.
145
DIFFERENT PATTERNS OF PAIN REFERRAL AND REGIONAL DEEP TISSUE HYPERALGESIA
IN EXPERIMENTAL HUMAN HIP PAIN MODELS
M. Izumi, K.K. Petersen, L. Arendt-Nielsen, T. Graven-Nielsen
Laboratory for Musculoskeletal Pain and Motor Control, Center for Sensory-Motor Interaction (SMI),
Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg,
Denmark
Background and aims: Hip disorder patients typically present with extensive pain referral patterns
and widespread hyperalgesia but the structures generating specific pain patterns are unknown. The
purpose of this study was to develop a novel human experimental hip pain model.
Methods: In sixteen healthy subjects pain was induced by hypertonic saline (1ml, 5.8%) injection into
the gluteus medius tendon (GMT), addutor longus tendon (ALT), and gluteus medius muscle (GMM).
Isotonic saline was injected contralaterally as control. Pain intensity was assessed on an electronic
visual analogue scale (VAS). Before, during and after the injection, pressure pain thresholds from the
lateral hip (PPTs), cuff algometry pain thresholds from the thigh (cuff PPTs), and passive hip pain
provocation tests were performed.
Results: Hypertonic saline injected into GMT caused higher VAS scores than injections into ALT and
GMM and compared with isotonic saline (P< 0.05). Referred pain areas to large parts of the leg were
found after GMT and GMM injections compared with a more regionalised pattern after ALT (P< 0.01).
PPTs were decreased after GMT and GMM hypertonic saline injections compared with ALT while cuff
PPTs were decreased after ALT injection compared with GMT (P< 0.05). More subjects had positive
pain provocation tests after hypertonic compared with isotonic saline injections (P< 0.05).
Conclusions: The experimental hip models showed regional hyperalgesia and pain referrals similar
to hip pain disorders. This novel model may open for a better understanding of the pain mechanisms
in hip pain conditions and the structures generating specific pain patterns.
146
EXPERIMENTAL KNEE PAIN REKINDLES SPREADING HYPERALGESIA AND FACILITATED
TEMPORAL SUMMATION OF PAIN IN PATIENTS WITH KNEE OA
1,2
1
1
1
1
T.S. Joergensen , M. Henriksen , S. Rosager , L. Klokker , K. Ellegaard , B. Danneskiold1,2
1,2
2
Samsoe , H. Bliddal , T. Graven-Nielsen
1
Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, The
2
Parker Institute, Frederiksberg, Department of Health Science and Technology, Center for SensoryMotor Interaction (SMI), Aalborg University, Aalborg, Denmark
Background and aims: Intraarticular injections of glucocorticosteroid have been shown to reduce
pain in knee osteoarthritis. This study aimed to assess peripheral and central pain sensitisation in
knee OA patients, after a period of reduced pain by anti-inflammatory treatment, and subsequently
after experimental knee pain.
Methods: Ten knee osteoarthritis patients received intraarticular injections of glucocorticosteroid into
the most affected knee to reduce the pain intensity assessed on a numerical rating scale. After two
weeks the patients were exposed to experimental pain by injection of hypertonic saline into the
infrapatellar fat pad of the knee previously receiving glucocorticosteroid and a control injection of
isotonic saline was performed after at least one week (sequence randomised). Pressure pain
thresholds (PPTs) and temporal summation of pressure pain (TS) on the knee, leg and arm were
assessed before glucocorticosteroid and before, during and after the experimental pain and control
conditions.
Results: Compared with pre-treatment, glucocorticosteroid reduced the osteoarthritic pain intensity
and hyperalgesia (P< 0.0001). Compared to isotonic saline, the experimental knee pain model
reduced PPTs on the injected infrapatellar fat pad during pain (P< 0.0001) and facilitated TS during
pain at the infrapatellar fat pad, m.vastus lateralis, and m.tibialis anterior (P< 0.0001).
Conclusions: Acute experimental knee pain induced in knee OA patients after a 2-week period of
pain relief caused hyperalgesia and facilitated temporal summation in the knee and in knee-related
muscles. The novel results of the present study illustrate that the dynamics of the nociceptive system
in knee OA patients may be modulated.
147
ETHNOMEDICINAL PLANTS FROM NORTH TARAI FORESTS OF (U. P.) INDIA FOR JOINT &
MUSCLE PAIN
T.P. Mall, S. Sahani
Postgraduate Department of Botany, Kisan P. G. College, Bahraich, India
The North Tarai region of U.P. (India) offers a great scope for ethnobotanical studies due to its
phytodiversity, a large tribal community and ethnic culture, brought to light a number of plant species
used as herbal medicines for the treatment of joint pain, muscle pain as well as rheumatic and arthritic
pain.The present report elucidates a rich and unique profile of sixty eight plant species belonging to
sixty genera representing thirty four families for joint pain, muscle pain as well as & rheumatic pain
viz. Acorus calamus, Ageratum conyzoides , Allium cepa ., A. sativum, Aloe vera , Alstonia scholaris,
Anisomela indica, Asparagus racemosus, Brassica compestris., B. juncea, B. oleracea., Boerhavia
diffusa, Calotropis procera, Cardamine scutata, Carica papaya, Carum copticum, Callicarpa
macrophylla, Cassia fistula, Centella asiatica, Cannabis sativa, Chenopodium