Diagnosis and
Management of
Craniofacial Pain
Richard K. Osenbach, M.D.
Director, Neurosurgical Services
Cape Fear Valley Medical Center
Key Points
All facial pain IS NOT trigeminal neuralgia
There are no tests for trigeminal neuralgia or for that
matter most causes of facial pain
The wrong diagnosis can lead to the wrong treatment
Despite all the advancements in medicine, it is not possible
to cure all pain problems
Approach to the patient with craniofacial pain
Specific pain syndromes
Pharmacological Management
Surgical Treatments
Approach to the Patient with
Craniofacial Pain
Single most important aspect is to ESTABLISH THE
CORRECT DIAGNOSIS
Careful detailed pain history
Location
Duration
Temporal characteristics
Quality
Severity
Circumstances of onset
Influencing factors
Neurological symptoms
Response to medications
The more paroxysmal the pain, the more likely that
surgery may be beneficial
Neuropathic Craniofacial Pain
Syndromes
Trigeminal neuralgia
Sphenopalatine neuralgia
Trigeminal neuropathic
Vidian neuralgia
Postherpetic trigeminal pain
Superior laryngeal neuralgia
Glossopharyngeal neuralgia
Carotidynia
Geniculate neuralgia
Occipital neuralgia
Headache Syndromes
Classic migraine
Common migraine
Migraine variants
Chronic daily headache
Cluster headache
Muscle tension headache
Post-traumatic headache
Chronic paroxysmal hemicrania
Headache caused by other disorders
Eg. Brain tumor, hydrocephalus, etc.
Ocular and Periocular Disorders
Tolosa-Hunt Syndrome
Raeder’s paratrigeminal syndrome
Orbital apex syndrome
Cavernous sinus syndrome
Parasellar syndrome
Corneal pathology
Angle closure glaucoma
Optic neuritis
Orbital cellulits
Otologic Problems
Otitis externa and interna
Ramsey-Hunt Syndrome
Bullous myringitis
Tumors
Mastoiditis
Dental and Periodontal Pathology
Periodontal abscess
Bruxism
Burning mouth syndrome
Temporomandibular joint disorders
What’s The Point?
SUCCESSFUL
TREATMENT DEPENDS
ON MAKING THE
CORRECT DIAGNOSIS
Classification of Facial Pain
Trigeminal neuralgia, type 1, (TN1): facial pain of spontaneous onset with greater than
50% limited to the duration of an episode of pain (temporary pain).
Trigeminal neuralgia, type 2, (TN2): facial pain of spontaneous onset with greater than
50% as a constant pain.
Trigeminal neuropathic pain, (TNP): facial pain resulting from unintentional injury to
the trigeminal system from facial trauma, oral surgery, ear, nose and throat (ENT)
surgery, root injury from posterior fossa or skull base surgery, stroke, etc.
Trigeminal deafferentation pain, (TDP): facial pain in a region of trigeminal
numbness resulting from intentional injury to the trigeminal system from neurectomy,
gangliolysis, rhizotomy, nucleotomy, tractotomy, or other denervating procedures.
Symptomatic trigeminal neuralgia, (STN): pain resulting from multiple sclerosis.
Postherpetic neuralgia, (PHN): pain resulting from trigeminal Herpes zoster outbreak.
Atypical facial pain, (AFP): pain predominantly having a psychological rather than a
physiological origin
Pharmacological Therapy
Anti-epileptics drugs (AEDs)
Antidepressant medications
Opiates
Neuroleptics
Antispasmodics
Miscellaneous drugs
Botox
General Principles of
Pharmacological Management
Rule out surgical lesions (tumor, etc.)
Neuropathic vs. nociceptive?
Develop a strategy
Lay out a plan
Conservative initial dosing to avoid side effects
Monotherapy is preferable if possible
Escalate dose to effect or toxicity
If second drug needed, choose agent in different class
Na+ channel blcoker, GABA agonist, etc.
Antiepileptic Agents
Tegretol (carbamazepine)
Topamax (topirimate)
Trileptal (oxcarbazepine)
Lamictal (lamotrigene)
Neurontin (gabpentin)
Keppra (levateracitam)
Lyrica (pregabalin)
Gabatril
Dilantin (phenytoin)
Benzodiazepines
Depakote (valproic acid)
Antiepileptic Drugs (AEDS)
Similarities in pathophysiology of neuropathic pain and epilepsy
All AEDS ultimately act on ion channels
Efficacy of AEDS most clearly established for neuropathic
conditions characterized by episodic lancinating pain
Most clinical studies have focused on DPN and PHN
Use of AEDS in patients with FBSS is nearly entirely empiric
AEDS Studied in Neuropathic Pain
Mechanisms of Selected AEDS
Carbamazepine (Tegretol)
Modulates voltage-gated Na+ channels
Reduces spontaneous activity in experimental neuromas
Inhibits NE uptake; promotes endogenous descending inhibitory mechanisms
Oxcarbazepine (Trileptal)
Modulates Na+ and Ca+2 channels, incease K+ conductance
Lacks toxicity of epoxide metabolites
Lamotrigine
Blocks voltage-gated Na+ channels
Inhibits glutamate release from pre-synaptic neurons
Gabapentin (Neurontin)
Structural analog of GABA
Binds to voltage-dependent calcium channels
Inhibits EAA release; Interacts with NMDA receptor at glycine site
Pregabalin (Lyrica)
Binds to voltage-gated calcium channels
Adverse Effects of AEDs
Allergic reaction
Up to 7% with CBZ
Some cross-reactivity between CBZ and PHT
Cognitive changes
Sedation
Nystagmus, ataxia, diplopia, dizziness
Nausea, vomiting, headache
nd
2
Adverse Effects of
AEDS
Generation
Antidepressant Analgesics
“The results suggest to us that antidepressants may
have an analgesic action which is independent of
their mood-altering effects”
Merskey & Hester 1972
Descending Pain Modulation
Endorphin link from PAG to pontine
raphe nuclei
Serotonergic conection to spinal dorsal
horn
Noradrenergic pathway from locus
ceruleus to dorsal horn
Antidepressant Analgesics
Current Evidence
Relieves all components of neuropathic pain
RCT - clear separation of analgesic and antidepressant
effects
Although other agents (eg anti-epileptics)) may be regarded
as 1st line therapy over antidepressants, there is no good
evidence for this practice
More selective agents are either less effective or not useful
(serotonergic, noradrenergic)
Because of incomplete efficacy, combination therapy may
be needed
Comparative data regarding other drugs using NNT figures
now exists
Antidepressants in Neuropathic Pain-RCT
Watson et al.: reviewed 29
randomized clinical trials
100
16 involved PHN or PDN
Mixed SN agents – 18/21 + effects 80
86
Amitriptyline 10/13, Imipramine
5/5,Doxepin 1/1, Venlafexline 60
2/2
NA – 10/12 + effects
40
Nortriptyline 3/4, desipramine
4/5, maprotiline 2/2, bupropion
20
1/1
Serotonergic agents – 4/5 + effects
0
Paroxetine 1/2, clomipramine
Mixed NS
2/2, citalopram 1/1
83
NA
80
Ser
Adverse Effect of Antidepressants
Anti-cholinergic autonomic effects (TCAs)
Allergic and hypresensitivity reactions
Cardiovascular effects
Orthostatic hypotension (avoid imipramine in elderly)
Quinidine-like cardiac effects
CNS effects
Sedation, tremor, seizures, atropine-like delerium,
exacerbation of schizophrenia/mania
Acute overdose may be fatal (>2000mg)
Withdrawal reactions
Guidelines for Use of Antidepressants
in Pain Management
Eliminate all other ineffective analgesics
Start low and titrate slowly to effect or toxicity
Nortriptyline or amitriptyline for initial treatment
Move to agents with more noradrenergic effects
Consider trazadone in patients with poor sleep pattern
Try more selective agents if mixed agents ineffective
Do NOT prescribe monoamine oxidase inhibitors
Tolerance to anti-muscarinic side effects usually takes
weeks to develop
Withdraw therapy gradually to avoid withdrawal syndrome
Opioids for Chronic Non-Malignant
Pain
Well-established and accepted for acute/cancer pain
Extrapolation of outcomes to non-malignant pain flawed
Information is more anecdotal, contradictory, philosophical,
and/or emotional than scientific
Limited number of well-designed RCT with inconclusive
results
Reduction in pain scores of around 20% without major
benefits on function or psychological outcomes
Principles of Opioid Therapy in
Chronic Non-Malignant Pain
Opioids provide analgesic benefit for a selected
subpopulation of patients
Less evidence exists regarding improvement in function
Benefits outweigh risks in well-selected patients
Most benefit in patients with pain from established
nociceptive/neuropathic conditions
Identification of other appropriate patients is problematic,
and valid diagnostic criteria do not exist
Implementation of Opioid Therapy
Prerequisites
Failure of pain management alternatives; but not a last resort
Opioids should only be use as part of a multimodality approach
Identification of realistic goals of treatment
Physical and psychosocial assessment by multidisciplinary team
Consider history of substance abuse as a relative contraindication
Decision to prescribe by multidisciplinary team or at least two
practitioners
Informed written consent
Best practice – prescribe a trial of opioids and withdraw use if the
provision of analgesia does not result in functional improvement
Implementation of Opioid Therapy
Therapeutic Trial Period
Appropriate oral or transdermal drug selection
Defined trial period with regular assessment and review
Opioid dose adjustment or rotation as needed
Decision for long-term treatment predicated upon
demonstration of pain relief and/or functional improvement
Implementation of Opioid Therapy
Long-Term Therapy
Opioid contract
Single defined prescriber
Regular assessment and review
Routine urine and serum drug screen
Ongoing effort to improve physical, psychological,
and social function as a result of pain relief
Continued multidisciplinary approach to pain
Defined responses to psychosocial or behavioral
problems (addiction, diversion, etc)
Opioid Therapy - RCT
Pain Type
Nociceptive
Neuropathic
Idiopathic
Unspecified
Study
Control
Results
Arner & Meyerson, 1988
Placebo
Pos
Kjaersgaard-Anderson, 1990
Paracetamol
Pos***
Arner & Meyerson, 1988
Placebo
Neg
Dellemijn & Vanneste, 1997
Placebo/Valium
Pos
Kupers, et al., 1991
Placebo
Pos
Rowbotham et al., 1991
Placebo
Pos
Arner & Meyerson, 1988
Placebo
Neg
Kupers, et al., 1991
Placebo
Neg
Moulin et al., 1996
Benztropine
Pos***
Arkinstall et al., 1995
Placebo
Pos***
Mays et al., 1987
Placebo/Bupiv
Pos
Opioid Therapy – Prospective
Uncontrolled Studies
Pain Type
Reference
Results
Nociceptive
McQuay et al., 1992
Pos
Neuropathic
Fenollosa et al., 1992
Pos
McQuay et al., 1992
Mixed
Urban et al., 1986
Pos
Idiopathic
McQuay et al., 1992
Neg
Mixed/Unspecified
Auld et al. 1985
Pos
Gilmann & Lichtigfeld, 1981
Pos
Penn and Paice, 1987
Pos
Plummer et al., 1991
Mixed
Adverse Effects of Opioids
Common
Nausea/vomiting
Constipation
Urinary retention
Sedation
Cognitive impairment
Pruritis
Occasional
Hallucinations
Myoclonus
Mood changes
Anxiety
Rigidity
Dry mouth
Gastric stasis
Bronchoconstriction
Rare
Respiratory dep.
Seizures
Delerium
Hyperalgesia
Allodynia
Tolerance, Physical Dependence, Addiction
Miscellaneous Agents
Antiarrhythmics - Mexilitene
Na+ channel blockade
Reduce neuronal hyperexcitability
Possible predictive effect of IV lidocaine challenge
May worsen AV conduction block
Monitor EKG, LFT, renal fxn
Significant incidence of treatment-limiting side effects
Baclofen
GABAB receptor antagonist
Efficacious in TN
Start 10mg QD and titrate until effect or sedation
Cannot abruptly withdraw drug!
Trigeminal Branch
Stimulation
Trigeminal Branch Stimulation
Stimulation of supraorbital, infraorbital nerves
Indications
Trigeminal neuropathic pain
Trigeminal deafferentation pain
Post-herpetic neuralgia
Chronic daily headache
Peripheral Trigeminal Branch Stimulation
for Neuropathic Pain
Johnson M, Burchiel K, Neurosurgery, 2004
6
5
4
2
4
0
0
25
50
75
100
3
Pain Relief
8
2
6
4
1
2
0
Increase
No Change
Medication Use
Reduced
0
Slightly
Somewhat
Mostly
Completely
Patient Satisfaction
Peripheral Trigeminal Branch
Stimulation for Neuropathic Pain
Effective for trigeminal
neuropathic pain
Less effective for PHN
Simple, low morbidity
Pain relief seems relatively
durable
Major problem is erosion of
connector
Motor Cortex Stimulation
Motor cortex stimulation is NOT FDA approved and represents an
off-label use of the implanted device
History of MCS
Developed by Tsubokawa and colleagues during 1980s
Treatment of central deafferentation pain
Poststroke pain
Thalamic pain
Bulbar pain
Alternative to other methods of neuromodulation for
SCS
DBS
Discovered that stimulation of motor rather than
sensory cortex produced better pain relief
Sensory
Cortex
Motor
Cortex
Sensory
Cortex
Inhibitory
Thalamus
Thalamus
Inhibitory
DCN
Dorsal
Horn
Nociceptive Input
(Spinothalamic System)
InInhibitory
Non-noxious Input
(DCML System)
Relationship Between Spinothalamic and DCML System - Normal
Thalamic Pain
A, C-fiber
PNS
A
Motor Cortex Stimulation
Clinical Indications
Post-stroke pain
Post-herpetic neuralgia
Trigeminal neuropathic pain
Trigeminal deafferentation pain
Transcranial Magnetic Stimulation
VAPSPre
VAPSPost
Sham
7.0 + 0.6
6.5 + 0.6
0.5 Hz TMS
6.4 + 0.7
5.5 + 0.7
10 Hz TMS
7.3 + 0.5
4.8 + 0.8
Localization of Motor Cortex
Complications
Stimulation-induced seizures
Pain at stimulation site
Epidural hematoma
CSF leak
Electrode fracture or migration
Infection
Results of MCS
Nguyen et. al.: Arch Med Res, 2000
32 patients with central or peripheral neuropathic pain
Mean follow-up 27 months
Substantial pain relief achieved in:
77% (10/13) with central pain
83% (10/12) with neuropathic facial pain
Satisfactory results in 1/3 patient with SCI pain, 1
patient with PHN, 1 patient with plexus avulsion
No patient developed seizures
Results of MCS
100
90
80
70
60
VAS score 50
40
30
20
10
0
Pre-Op VAS
VAS 3 months
VAS long-term
Unanswered Questions
What are the best indications for MCS?
What is the value of preoperative pharmacological testing?
Is there a predictive value to TMS?
What is the optimum electrode location?
Is there any value to using multiple electrodes?
Are there optimum stimulation parameters?
How often should stimulation be applied and for how
long?
Can long-term reduction in pain be explained by
adaptation of the brain to chronic stimulation?
Deep Brain Stimulation
Deep brain stimulation is NOT FDA approved for pain and
represents an off-label use of the implanted device
Stimulation-Produced Analgesia
Reynolds, 1969: science
Electrical stimulation of rat midbrain results in
profound analgesia without concurrent
administration of analgesic drugs
Relationship between SPA and endogenous
opioid system
Richardson, 1973
1st published report of PAG-PVG stimulation
in humans
DBS Pain Targets
PVG AND PAG
Activation of endogenous opiate systems
Descending modulatory pathways
Best for nociceptive pain
LEMNISCAL SYSTEM
Vc (VPL,VPm) nucleus, medial lemniscus, IC
Paresthesia-producing stimulation
Best for neuropathic pain
Results of DBS
Overall results variable
30% to 85% excellent/good pain relief
Richardson (Neurosurgery, 1977)
85% effective short-term; 65% at 1 year
Gybels & Kupers (Neurophys Clin, 1990)
initial 61%; 4 years 30%
Plotkin (Appl Neurophys, 1982)
60-65% good results
Results of Deep Brain Stimulation
Gybels and Kupers
Literature review through 1998
1,863 patients (38 reports)
Latest results analyzed
Success defined as:
Pain relief scores of 50% or more
Verbal ratings of “good” or “excellent”
Lack of relief during trial considered failure
Deep Brain Stimulation
Deafferentation Pain
Electrode Site
No.
Long-Term Success
%
PAG-PVG
155
35
23
VPL-VPM
409
228
56
Overall
644
349
54
Deep Brain Stimulation
Nociceptive Pain
Electrode Site
No.
Long-Term Success
%
PAG-PVG
291
247
59
VPL-VPM
51
0
0
Overall
419
172
59
Pain Type vs. Site of Stimulation
60
50
40
Success Rate 30
20
10
0
Nociceptive pain
PAG-PVG
VPL-VPM
Deafferentation pain
Overall
Deep Brain Stimulation
Complications
Neurologic
Intracranial hemorrhage
1 - 5%
Infection
3 -14%
Seizures
3 - 4%
Device-related
2 - 26%
Lead fracture
Lead migration
Stimulation-related
Usually transient, resolve with adjustments to stimulation
Headache, nausea, diplopia, vertica gaze palsy, nystagmus,
uncomfortable paresthesias, unpleasant stimulation side effects
Cluster Headache
Unilateral headache syndrome
Pain mainly located in orbitotemporal region
Abrupt onset and cessation
Pain last 15 – 3 hours (HIS criteria)
One or multiple attacks per day
Autonomic symptoms
“Cluster periods” lasting weeks to months
Episodic or chronic forms
Surgical Treatment for Cluster
Headache
Microvascular decompression of trigeminal nerve
Ablative trigeminal procedures
RF rhizotomy
Glycerol rhizolysis
Stereotactic radiosurgery
Section of nervus intermedius
Destruction of sphenopalatine ganglion
Deep brain stimulation
Proposed Eligibilty Criteria for
DBS in Patients with Cluster HA
Diagnosis of CH according to HIS criteria
Symptoms present at least 24 months
CH attacks on daily basis
Symptoms strictly unilateral
All state-of-the-art medications have been tried singly
or in combination
“Normal psychological profile
No medical/neurological contraindications to DBS
Normal neurological exam and imaging studies
Patient agrees to discontinue smoking and/or EtOH
consumption
DBS for Cluster Headache
“Stimulation of the Posterior Hypothalamus for Treatment of Chronic Intractable Cluster
Headache: First Reported Series” Neurosurgery (2003)
Stim. Parameters: Amp=.7-3V, PW=60, Rate=180 Hz
Nucleus Caudalis DREZ
Procedure
Indications for Caudalis DREZ
Trigeminal deafferentation pain (following RF lesion)
Recurrent refractory trigeminal neuralgia
Trigeminal neuropathic pain (post-traumatic)
Post-herpetic neuralgia
Central pain following brainstem infarction
Cluster headache
Intractable migraine headache
Atypical facial pain
Cancer pain
Anatomical Landmarks
Caudalis DREZ Results
VAS Scores
10
9
8
7
6
VAS Score 5
4
3
2
1
0
Pre-op VAS
Post-op VAS
AFP
PHN
TN
Overall
7.6
6.1
9.5
6.6
8.7
8.4
8.8
7.6
Caudalis DREZ Results
Percent Improvement
70
60
50
40
30
20
10
0
Immediate
Late
AFP
PHN
TN
Overall
69
48
42
41
14
29
32
30
Occipital Neuralgia and
Occipital Headache
Syndromes
Occipital Neuralgia
Pain within the distribution of the greater and/or lesser occipital
nerves
Neuralgic variant
Sharp, shooting, electric-like pain
Almost always unilateral
Bursts of pain lasting for several seconds to few minutes
Non-neuralgic variant
Dull, aching, throbbing, pounding pain
More constant pain
Often bilateral
Sensory dysfunction in C2 nerve territory
Responds to local blockade of occipital nerve
Causes of Occipital Neuralgia
Idiopathic
Post-traumatic
Spinal Disorders
C1 fracture
C1-2 instability
RA with cranial settling
C1-2 arthrosis
syndrome
Hypertrophic facet joint
Inflammatory disorders
Post-Operative
VP shunt
Retromastoid
craniectomy
Mastoidectomy
Chiari malformation
Metabolic disorders
Vascular lesions
Tumors
Evaluation: Plain X-rays, CT, MRI
Chiari I Malformation
Basilar Invagination
Schwannoma of GON
Intradural Schwannoma
Chronic Daily Headache
Chronic migraine subset
Headache present at least 15 days per month
Near daily to continuous pain
Incidence 4% to 5%
Up to 50% unresponsive to medication
OCCIPITAL NERVE
STIMULATION FOR OCCITAL
HEADACHE SYNDROMES
Indications for ONS
Appropriate clinical condition
Condition refractory to non-operative therapy
Acceptable psychological profile
Positive response to local anesthetic block
Positive response to temporary stimulation trial
ONS - Technique
ONS – Electrode Position
Complications of ONS
Infection
Connector erosion
Electrode migration
Electrode fracture
Motor stimulation
Stimulation tolerance
Occipital Nerve Stimulation
Outcome
130 patients
Average duration of symptoms – 8 years
Unilateral – 88; Bilateral – 42
Mean VAS score – 9.2 (5-10)
Weiner, R
Results of ONS
50
10
45
9
40
8
35
7
30
6
25
5
20
4
15
3
10
2
5
1
0
0
Excellent
Good
Fair
Poor
Pre-Op VAS
Post-Op VAS
Chronic Migraine
Cluster Headache
(May, Bahra, Buchel, Frackowiak & Goadsby, Lancet 1998)