Complex regional pain syndrome(CRPS)
Introduction
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Abnormal post traumatic pain following any nerve injury
3 basic criteria for diagnosis (American Association for Hand Surgery)
1. Disproportionate pain
 hyperpathia -prolonged pain after stimulation
 allodynia -marked pain from a usually nonpainful simulation
 pain is usually constant.
2. Interference with function
3. Autonomic-type abnormality (eg, skin discoloration, sweating, dryness,
edema, temperature change, osteoporosis)
CRPS (International Pain Nomenclature Group task force 1996) - defined on
purely clinical grounds
CRPS is a clinical diagnosis – there are no physiological markers
CRPS is initiated by trauma, compounded by post traumatic event(tight cast) ,
and exacerbated by pre-morbid physiological state
Early recognition and prompt treatment is the single most important
predictor of recovery
1. 80% pts with RSD diagnosed within 1 yr of injury show significant
improvement
2. 50 % pts diagnosed after 1 yr have significant impairment
Classification
 2 major categories and three types
1. Sympathetically maintained pain syndrome (SMP)
 pain that is maintained by sympathetic efferent innervation and or circulating
catecholamines
 responds to sympathetic blocks
 seen in Types I and II
2. Sympathetically independent pain syndrome (SIP)
 Does not respond to sympathetic block
 Seen in Type III
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Clinically patients may have varying components of SMP and SIP throughout the
course of the disease
Type I (classically “reflex sympathetic dystrophy”) follows an initiating noxious
event
 Pain - Continuous pain or allodynia and hyperpathia is not limited to the territory
of a single peripheral nerve and is disproportionate to the inciting event
 Functional Impairment
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Autonomic dysfunction - Edema, skin blood flow abnormality, abnormal
sudomotor activity, and motor dysfunction are disproportionate to the inciting
event
Exclusion - Diagnosis is excluded by the existence of conditions that would
otherwise account for the degree of pain and dysfunction
Type II (classically described “major causalgia”) includes the following
 Nerve injury - Major nerve injury, more regionally confined presentation
(usually), principally involving the territory of the involved nerve
 Pain - Spontaneous pain or allodynia and hyperpathia usually limited to the area
involved but may spread distally or proximally
 Functional impairment
 Autonomic dysfunction -Edema, blood flow abnormality, or abnormal
sudomotor activity is or has been shown in the region of pain subsequent to the
inciting event, or there is motor dysfunction disproportionate to the inciting event
 Exclusion -Diagnosis is excluded by conditions that otherwise account for the
degree of pain and dysfunction
Type III (sympathetically independent pain)
 classification identifies cases of disproportionate pain and sensory change with
motor and tissue change that do not respond to sympathetic block.
Pathophysiology
 Normally pain is felt in the presence of actual or impending cellular injury , in the
absence of trauma persistent pain is pathological
 Proinflammatory cells like lymphocytes and mast cells accumulate in the affected
tissue, releasing cytokines and histamine, and activate inflammatory mediators,
such as prostaglandins, which are responsible for sensitizing C nociceptor
afferent nerve endings
 This information is transmitted to the dorsal root ganglia where sensitization of a
wide dynamic range of neurons (WDR) contributes to the central nociceptive
discharge.
 Within the dorsal horn, NMDA receptor transmitter interactions produce long
lasting potentials , is refractory to stimulation and is theorized to play a role in
CRPS I and II
 The perception of pain is determined by complex interaction of afferent,
descending modulatory pathways and peripheral and central factors
 Vasomotor disturbances can result from a variety of mechanisms including
antidromic vaso dilation, vasoparalytic dilatation, normal somatosensory reflexes
and denervation supersensitivity
 Abnormalities:
1. abnormal neurotransmitter release secondary to nociceptive foci
2. abnormal receptor distribution
3. alterations in receptor sensitivity (up-or-down regulation)
 Following trauma a transient period of dystrophic extremity function is normal
 It is abnormal for hyperpathia, allodynia, vasomotor disturbances and functional
deficiencies to persist
 Theories
1. Exaggerated and sustained normal inflammatory response
2. Backflow of nociceptive stimuli into the injured area releasing vasoactive
neuropeptide substances ie substance P, calcitonin gene-related peptide,
bradykinin, serotonin, somatostatin, neurokinin A, and others
a. Substance P especially has been shown to cause vasodilatation,
increased vascular permeability, pavementing of leukocytes in
venules, stimulation of phagocytosis, degranulation of mast cells,
and stimulation of fibroblasts.
3. Altered response by sympathetic nervous system
a. this concept being increasing challenged
b. Experimental findings do not show hyperactivity of the
sympathetic nervous system
c. placebo-controlled studies showed sympathetic block to be no
more effective than the placebo
d. autonomic dysfunction now thought to either be sensitisation of
sympathetic nervous system by local neuropeptides or mediated by
neuropeptides themselves
4. Psychological
a. CPRS patients are more likely to be anxious, depressed, more
dissatisfied with their bodies
b. most investigators believe these psychologic differences are a
result rather than a cause of RSD
Demographics
 most reports average about a 5% incidence after an inciting cause
 The more common injuries and surgery, such as Colles fracture and carpal
tunnel syndrome, have the highest frequency of cause
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10% to 30% of patients have spontaneous occurrence with no evident
precipitating cause or condition
F>M 3:1
mean age 45 (35-50); has been reported in children
increased incidence of cigarette smoking
Psychological factors such as stressful life event, and inadequate coping
mechanisms influence the development and severity
No specific personality or psychological factor has been predisposed
individual to CRPS
Prognosis
 Most patients with Type 2 will improve with time
 in other forms of RSD-CRPS, complete remission is rare
 incidence of recurrent or migratory RSD is reported to be as high as 15% to
75%, often occurring at a different site
 Overall, review of the literature gives the impression that most treatment
methods result in approximately one third of patients with excellent to
good relief, one third with some improvement, and one third with no
improvement or worsening of symptoms.
Aetiology
 Most common are
1. Colles fracture –11-37%
2. Carpal tunnel surgery 2-5%
3. Surgical trauma to superficial radial nerve and palmer branch of radial nerve
4. No cause in 30%
Clinical
Symptoms
 most characteristic clinical feature of RSD is the peculiar disproportionate
unremitting pain.
o hyperpathia and allodynia
 pain is constant and not completely relieved by rest, and it is aggravated by
motion; activity; or temperature change (especially cold).
 Mirror image (advancement to the contralateral extremity) up to 25%
Signs
 first noticeable physical findings in RSD is the patient's avoidance of touch or
functional use caused by pain
 Trophic changes
1. Stiffness (70%) - passive better than active range of motion until late changes
occur
2. Oedema – gives a glossy smooth appearance to skin
3. Atrophy of hair and nails(or hyperkeratosis)
4. Atrophy of intrinsics may be seen
5. Osteopenia involving cortical and cancellous bone
6. Autonomic changes
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a. vasomotor changes include skin discolouration (mottled color change
(redness or cyanosis))
b. difference in skin temperature - warmness more common early and
coolness later in the course of the disorder
c. hyperhydrosis or dryness
7. Motor disturbances
a. Tremor (58%)
b. weakness
c. incoordination dystonia (35%)
d. decreased ROM
need to examine the cervical spine and neurological system to exclude other
causes eg diabetes, small fibre peripheral neuropathies, entrapment neuropathies,
thoracic outlet syndrome, DVT and cellulitis may all mimic CRPS, and assess
shoulder as frozen shoulder can occur secondarily
look for myofascial trigger points – 50-70% incidence in CPRS patients
3 distinct clinical forms
1.
CRPS Type 2
 caused by partial injury to a proximal major mixed nerve
 onset is immediate and its course usually includes some degree of
spontaneous improvement
 superior response to sympathetic block and sympathectomy
 Nerve injuries are usually above the elbow and knee, and are
most often caused by high-velocity missile wounds
 Sympathetic block usually provides temporary relief of causalgia
and repeated blocks may produce sustained relief in some cases
 When only temporary relief consistently results, surgery is
indicated, with sympathectomy remaining the treatment of choice
2.
Shoulder-hand syndrome
 pain of RSD originating in the shoulder, progressing distally
 need to exclude Pancoast's tumor and visceral tumors
3.
Sudeck's osteoporosis/atrophy
 resembles the osteoporosis of disuse but onset of osteoporosis is
much more rapid than can be explained by simple disuse, with
findings as early as 4 to 6 weeks after onset of symptoms
 consider calcitonin or bisphosphonate therapy, which may
reverse the osteoblastic activity and the pain in Sudeck's
osteoporosis
Stages of CRPS
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Patients have enormous variation in their presenting symptoms, duration, and
mixture of characteristics in each stage.
Many never progress beyond stage I, whereas others may rapidly progress to the
dystrophic stage III within 3 to 6 months.
These stages have no great clinical value, other than as a convenient description of
the clinical change and its prognostic implications
Stage I: acute
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Lasts approximately 3 months (variable)
Constant burning or throbbing pain (intensity varies), atrophy, and
hyperpathia
Trigger points may develop
Variable vasomotor changes, such as edema (aiding or nonprinting); color
change (usually redness, sometimes cyanosis); temperature change (usually
warming, sometimes coolness); increased sweating; sometimes dryness
Decreased joint range of motion caused by pain
Sometimes swollen fingernail ridging (occasional)
Increased hair growth or pigmentation (occasional)
Stage II: subacute
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Lasts approximately 9 to 12 months (variable)
Constant aggravating pain (intensity varies)
Atrophy of skin and subcutaneous tissue
Loss of fingertip pads (pencil pointing)
Glossy, thin skin
Decreased hair growth
Cyanosis
Brawny edema
Joint ankylosis
Palmar fasciitis and Dupuytren's nodules (occasional)
Myofascial trigger points (usual)
Subchondral patchy osteoporosis (usual)
Stage III: chronic
 Chronic intractable pain
 Pale, cool, dry extremity
 Thin, stretched skin
 Muscle atrophy
 Fixed flexion or extension contractures
 Diminished hair growth (usual)
 Patchy to generalized osteoporosis
 Patient is chronically depressed and may contemplate suicide
Diagnostic testing
 No one laboratory study is specific for RSD-CRPS, and it remains a clinical
diagnosis
 objective measurements are useful to support the diagnosis
 typical patients with RSD have normal sedimentation rate, C-reactive protein
level, leukocyte count, and concentrations of other acute-phase reactants, despite
the appearance of inflammation
Electromyographic and nerve conduction studies
 show no specific abnormality associated with RSD
Pain threshold evaluation
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Quantitiative sensory tests are available to test and compare the respond to painful
stimuli
Using monofilaments to assess hyperpathia and allodynia
Useful to monitor progress
use of a visual analog scale and a pain diagram drawn by the patient will add to
functional assessment
Thermography
 Temperature measurement by infrared thermography
 most useful to help the clinician communicate with the patient about the
illness and to monitor progress.
Radiology
1. Xray
 considerable demineralization must occur for osteopenia to become visible on
standard radiographic view which places patients at a late stage and a worse
prognosis
 also see diffuse juxtacortical demineralization and subchondral erosion and
cysts
2. three phase technetium bone scan
 in the phase III scan - diffuse tracer uptake in the delayed image is diagnostic
according to Mackinnon
 abnormalities seen in 50-80%
 A normal bone scan does not rule out the diagnosis
 useful test when positive, because it is seen well before standard radiographic
change
 positive scan has high specificity but low sensitivity
 bone scans is not a prerequisite for diagnosis, does not correlate with response
to treatment or predict recovery
Evaluation of autonomic control
 Autonomic function controls sweating and microvascular perfusion
 Evaluation of sympathetic control or dysfunction aids in diagnosis
 May be evaluated by testing microvascular flow or sweating
 Microvascular examination
1. Under normal circulation total digital flow is composed of 80 – 95 %
thermoregulatory flow and 5-20 % nutritional flow
2. In CRPS impaired autonomic control leads to ischaemia secondary to
reduced nutritional flow secondary to altered AV shunting
3. Analysed using microscopic epi-illumination of digital skin, combined
with laser Doppler flux
 Sudomotor evaluation
1. Galvanic skin conduction
2. Quantitative sweat response
Diagnostic sympathetic blocks
 Traditionally used as a diagnostic test
a. IV infusion of phentolamine (alphaadrenergic blockade) or regional
blocks stellate brachial plexus block
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More recent evidence refutes this and shows it no more effective than placebo
Treatment
 Multiteam approach with surgeon , therapist, pain specialist and psychologist
 Early diagnosis is paramount- there is general belief that the earlier treatment is
instituted, the better the prognosis
 all techniques are directed at interruption of the reflex pain cycle
Surgical treatment
1. Sympathectomy
a. useful in well-selected patients, especially in cases with proximal nerve
injury (causalgia)
b. The patient most likely to benefit from sympathectomy is one who obtains
repeated, dramatic, temporary relief from sympathetic blocks but for
whom the relief never lasts longer than the duration of the anaesthetic and
in whom there is no placebo effect with use of saline for the block.
2. Surgery for neural dystrophic focus
a. Principles
i. need for urgent surgery to avoid a severe chronic pain syndrome
ii. Use long-acting or continuous axillary block anaesthetic to
avoid redevelopment of a pain reflex cycle – shown to be effective
iii. Extensile exposure
iv. Avoid tension on nerve repair site – use grafts if required
v. Prevent adhesion between skin and nerve – Z plasty, local flaps
vi. If wound bed scarred, modify the bed
vii. Minimise internal neurolysis
viii. Prevent hematoma
ix. Avoid constrictive postoperative dressing
x. Postoperative pain control
b. Post carpal tunnel
i. Preserve palmar cutaneous branch
ii. Identify all branches
iii. Treat neuroma by relocation or repairing if in continuity
iv. If bed scarred, then modify local environment
1. autologous vein wraps – neuroma of palmar cutaneous
nerve or branches of median nerve in palm
2. local flaps – PB, ADQ, PQ, lumbricals, hypothenar fat pad
3. regional flaps – fasciocutaneous, fascial
c. Superficial branch radial nerve
i. Identify nerve proximal and distal to scar
ii. Options
1. nerve repair with graf
2. relocate into muscle/radius
3. cephalic vein wrap
3. Secondary joint deformities
a. Contemplate after maximal nonoperative improvement has been obtained
b. Minimum 3-6 months
c. Indications are joint pain without diffuse dystrophic symptoms and
arthrofibrosis interfering with function
4. Implanted electrical stimulation
a. improvement by peripheral nerve block is a prerequisite, along with
temporary success by transcutaneous nerve stimulation
b. best results when used in patients whose pain is “somatically” derived and
not from “sympathetic overstimulation/RSD.”
Nonsurgical treatment
1. Hand therapy
a. foundation of treatment for most patients with RSD-CRPS
b. other modalities should serve as adjunct
c. imperative to establish baseline measurement criteria to monitor progress
d. these patients typically do not believe they are slowly improving until
shown proof through objective measurements, such as reduced edema,
increased grip strength, improved range of motion, temperature control,
and so forth.
e. Techniques
i. “Rest and motion” are management principles that emphasize the
need for partial rest in a splinted functional position and frequent
physical activity and motion to the fullest pain-free extent
ii. Heat to relax muscle spasm and improve joint motion
iii. Treat myofascial trigger points with warm massage, stretch
exercises, and injection of persistent trigger points
iv. ultrasound over the stellate ganglion or the involved peripheral
nerve
v. biofeedback - temperature biofeedback – most useful when clinical
manifestations include pronounced temperature change
vi. desensitization
vii. stress loading
2. Stellate ganglion and other nerve blocks
a. remains the most widely accepted form of RSD-CRPS treatment
b. blocks are not uniformly successful and are no longer required for
diagnosis, although widely used to classify sympathetically maintained
pain (CRPS type I or II)
c. best suited for patients whose manifestations seem predominantly
sympathetic, such as abnormal skin color, temperature, and sweat
d. usually injected with local anaesthetic
e. results verified by
i. Horner’s syndrome
ii. Increase in skin temperature, venous engorgement, dry skin,
mottled color, laser Doppler flux changes
f. Reflex pain firmly established at the central level is more likely to respond
to other methods that activate the endogenous opioid internal pain control
system, which is known to interfere with pain neurotransmitter production
and secretion (eg, substance P). This endogenous mechanism might
explain why “placebo blocks” are frequently successful in as many as 30%
of patients
g. Brachial plexus blocks are useful to determine whether a patient's stiffness
is caused by pain or fibrosis by assessing the passive range of motion
while they are anesthetized and paralyzed.
h. Repeated local long-acting nerve blocks are sometimes successful in
breaking the pain cycle in selected patients whose symptoms are confined
to a specific neurologic region, (ie superficial radial nerve, or an isolated
digit, such as an amputation stump with painful digital neuroma.)
3. Intravenous regional infusions
a. infusion of intravenous guanethidine sympathetic block into an extremity
isolated by Bier block
b. Other common agents are reserpine, phentolamine, steroids and bretylium
but no conclusive evidence
c. Recent randomized, double-blind controlled comparison of intravenous
guanethidine, reserpine, and saline showed no difference at 24 hours.
Similar studies using phentolamine showed no advantage over placebo. As
yet, there has been no controlled study of bretylium tosylate
4. Systemic intravenous infusion
a. Lignocaine
i. Shown to relieve neuropathic pain and/or pain refractory to opioid
therapy
ii. antihyperalgesic effects on the peripheral as well as the central
nervous system
iii. membrane stabilising effect
5. Medical treatment
1. sympatholytics
a. clonidine (α2-adrenergic agonist), phenoxybenzamine (combined α1and α2-antagonist)
2. Calcium channel blockers
a. Nifedipine, diltiazem (verapamil has predominantly cardiac effect and
is not useful for RSD-CRPS)
b. function to decrease sympathetic smooth muscle tone and improve
blood flow, warming digits by preventing calcium release and reducing
vasoconstriction.
3. NSAIDS
a. of questionable value
4. Steroids
a. Proven beneficial in some patient - either with a short-term, high-dose
method or with long-term use
5. Central acting agents
a. anticonvulsants – postulated to stabilise excitable nerve membrane
and reduce hyperexcitability (Clonazepam, gabapentin)
b. baclofen (GABA agonist) – useful for ongoing muscle spasms and
cramps
c. recently intravenous infusion of Alendronate has been shown to reduce
pain and swelling and increasing ROM iin pts with CRPS
6. Antidepressants, anxiety, narcotic, and sleep medications
a. antidepressants(TCA) – provide analgesia and modulate sympathetic
over activity
b. narcotics - One should exhaust other treatment techniques before
resorting to chronic narcotic use.
7. Calcitonin
a. regulates bone metabolism
b. better results are reported when patients are treated soon after onset
c. best suited for patients with positive three-phase bone scan
8. Biphosphonates
a. by reducing local acceleration of bone remodelling - potent osteoclast
blocking agents and their believed action to inhibit neuropeptide
release from afferent nerve endings
b. most suitable in patients with abnormalities on bone scan
6. TENS
a. mechanism is hypothesized to be by activation of the endogenous opioid
analgesic system to release endorphins that may inhibit pain at the level of
the spinothalamic tract
b. particularly useful when there are minimal inflammatory or autonomic
changes and pain is the predominant manifestation.
c. generally used as adjunctive therapy to assist with pain control.
d. most effective when initiated early.
7. Acupuncture
a. Using electrodes or transdermal needles
b. Better results in Asian patients (?due to higher expectations)
Principles in the treatment of RSD
1. The best treatment is prevention
a. Effective intra and postoperative pain control
b. Early active movement
c. Avoid external fixation
d. Remove painful casts
e. Avoid painful therapy
f. Block patients with history of RSD
2. The earlier the treatment, the better the prognosis.
3. Individualize treatment methods to the particular patient's
manifestations.
a. sympathetic blocks, for example, if sympathetic symptoms
predominate
b. Temperature biofeedback treatment when there is major temperature
change.
c. Inflammatory symptoms – short term steroids
d. Central pain - TENS, antiepileptic medication (eg, gabapentin),
hypnosis, acupuncture, and stress loading
e. Sudeck’s atrophy - calcitonin or bisphosphonate
f. Hand thereapy for all
4. Start with the least invasive and morbid treatment techniques
5. Control the disproportionate pain and other marked symptoms of RSD
before elective surgery
a. long-acting blocks should be used during surgery to avoid exacerbating
RSD symptoms,
b. two situations in which surgery is clearly indicated for RSD,
i. RSD is associated with acute traumatic carpal tunnel syndrome
after injury, such as Colles fracture, emergent surgical release
of the carpal tunnel is indicated to avoid progressive dystrophic
change
ii. sympathetic blocks consistently relieve pain only to the time
limit of the block, at which point sympathectomy can then be
recommended.
6. Minimize stressful situations.
Prognosis
72 % continue to work and 26 % have to change jobs
30 % have to stop work for a period of time