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
Raeders 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

Whats 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

Adverse Effects of 2nd Generation

AEDS

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
16 involved PHN or PDN
Mixed SN agents 18/21 + effects
Amitriptyline 10/13, Imipramine
5/5,Doxepin 1/1, Venlafexline
2/2
NA 10/12 + effects
Nortriptyline 3/4, desipramine
4/5, maprotiline 2/2, bupropion
1/1
Serotonergic agents 4/5 + effects
Paroxetine 1/2, clomipramine
2/2, citalopram 1/1

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

Pain Relief

Medication Use

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

Sensory
Cortex

Motor
Cortex

Sensory
Cortex

Facilitation
Thalamus

Thalamus

Inhibitory

Thalamic Pain

DCN

Dorsal
Horn

InInhibitory

Nociceptive Input
(Spinothalamic System)

A, C-fiber

Non-noxious Input
(DCML System)

PNS

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

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

Overall

419

172

59

Pain Type vs. Site of Stimulation

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

Caudalis DREZ Results

Percent Improvement

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

Chronic Migraine

Cluster Headache

(May, Bahra, Buchel, Frackowiak & Goadsby, Lancet 1998)