Neuralgia

339

One of the most challenging clinical issues the dentistconfronts is the patient with persistent orofacial painwithout obvious proximate physical cause. Patientswith persistent pain often seek consultation from manyclinicians and undergo multiple unnecessary proceduresbefore receiving a correct diagnosis and appropriatetreatment. Clinicians unfamiliar with neuropathic painmay become frustrated and, with the best of intentionsbut limited information, provide familiar but inappro-priate treatment directed toward a dental or othersomatic pain. The spectrum and prevalence of orofacialneuropathic pains is such that every dentist will cer-tainly encounter patients with neuropathic pain. There-fore, to avoid unnecessary and inappropriate diagnosisand treatment, the dentist must gain familiarity with thepathophysiology, presentation, diagnosis, and treatmentof orofacial neuropathic pain.

By definition, neuropathic pain is nonadaptive anddoes not contribute to healing, such as would be the casewith pain attributable to tissue inflammation, wherepain results in adaptive behaviors, such as use limitation,guarding, rest, and avoidance, which contribute to heal-

ing. Neuropathic pain persists without real or potentialbenefit, resulting only in unnecessary suffering.

Somatic versus neuropathic pain

Somatic pain

As a first step toward understanding neuropathic pain it isimportant to recognize the fundamental differencebetween somatic and neuropathic pain. Somatic painalways results from stimulation of nociceptors, owing totissue injury. Nociceptors are the sensory receptors spe-cialized for detecting noxious thermal, mechanical, orchemical stimuli resulting from tissue injury. The neuro-immune interactions following tissue injury result in noci-ceptor sensitization such that the threshold for activationis reduced and the magnitude of response is increased.Thus, light touch in an area of inflammation or warmwater in contact with burned skin or mucosa becomespainful, not because the physical energy itself is noxious

Somatic versus neuropathic

pain, 339

Somatic pain, 339

Neuropathic pain, 340

Orofacial neuralgias, 340

Trigeminal neuralgia, 340

Clinical features, 340

Etiology, 341

Diagnosis, 341

Treatment, 341

Glossopharyngeal neuralgia,

342


Etiology, 342

Diagnosis, 342

Treatment, 342

Postherpetic neuralgia, 342


Etiology, 343

Diagnosis, 343

Treatment, 343

Nerve injury and neuroma

pain, 343


Etiology, 344

Diagnosis, 344

Treatment, 344

Phantom tooth

deafferentation pain, 344


Etiology, 345

Diagnosis, 345

Treatment, 345

Sympathetically maintained

pain, 346


Etiology, 346

Diagnosis, 346

Treatment, 346

Suggested reading, 347

32 Orofacial Neuralgias and Neuropathic PainDavid A. Sirois, DMD, PhD

340 C H A P T E R 3 2

but because the nervous system response is heightened.Primary hyperalgesia is the term used to describe theincreased perception of a painful stimulus followingreceptor sensitization; it is a hallmark of somatic pain.Allodynia refers to the perception of pain in response to anon-noxious stimulus; this too is often present during pri-mary hyperalgesia. Most somatic pains end when theunderlying tissue injury and inflammation resolves.

Neuropathic pain

Neuropathic pain is fundamentally different from somaticpain in that nociceptor stimulation is not necessary.Whereas tissue and nerve injury may initiate processesthat lead to pain, neuropathic pain persists once the initialinjury heals. Herein lies the diagnostic challenge, since inmost cases of neuropathic pain there is no evidence ofongoing tissue injury or inflammation to “substantiate”the pain, often leading to treatments directed at diseasethat does not exist (ie, endodontic therapy without pulpalinjury, tooth extraction without odontogenic disease).Allodynia and mechanical hyperalgesia are common fea-tures of neuropathic pain: the patient experiencesincreased pain to noxious stimuli as well as pain to non-noxious stimulation. Two general types of neuropathicpain exist: paroxysmal pain and continuous pain. Parox-ysmal pain refers to sudden, brief (seconds to minutes)but intense pain, which may be spontaneous or pro-voked by light touch or movement in the affected area.Continuous neuropathic pain has a constant burning orstinging quality that may have periods of greater orlesser intensity. Unlike somatic pain, paroxysmal neuro-pathic pain is characterized by pain-free intervals and,therefore, does not exhibit the same reliable provocationof pain upon stimulation. Furthermore, neuropathicpain does not necessarily occur in the area that evokesthe pain when stimulated; that is, there can be referral ofthe pain sensation to areas outside the stimulation zone.

A final note regarding the origins of sensation and per-ception is required before discussing specific neuropathicpain illnesses. Certainly, the vast majority of sensory per-ceptions are evoked by and accurately represent the actualphysical stimulus delivered. However, one must realizethat all perception is a product of neural activity in thecentral nervous system (CNS). Although most times theevoked CNS neural activity appropriately encodes a phys-ical stimulus, it is certainly the case that CNS activity inthe absence of an externally applied physical stimulus canlead to a sensory experience. It is well known that electri-cal stimulation of the CNS can produce vivid sensory per-ceptions in the absence of peripheral stimulation. Patho-logic processes that result in inappropriate CNS activitycan produce sensory perceptions that have no physicalcorrelate, yet they can be as real and valid as the sensoryperception evoked by a physical stimulus.

A dramatic illustration of the neurogenous origin ofperception is the common experience of phantom sen-sations and pains that follow amputation, where thereno longer exists a peripheral substrate (ie, arm, leg) forexperiencing the sensation. Bear in mind that the mostcommon amputation performed is pulp extirpation andtooth extraction, both of which can result in neuro-pathic phantom sensation and pain in a denervated ormissing tooth. The unorthodox yet undeniable factremains that one does not need to have a body part toexperience a sensation or pain from the correspondingregion, and there exist neural processes that can initiateand sustain a real perception in the absence of a physi-cal stimulus. Thus, the practitioner must accept whatthe patient says he or she is feeling as a real sensoryexperience with a physiologic, albeit not necessarilyphysical basis. Treating the neuropathic pain conditionas though the pain originates in the structures where thepain is perceived fails to recognize the neurogenousnature of neuropathic pain and often leads to inappro-priate and ineffective treatment. Instead, successfultreatment is that which focuses on eliminating or con-trolling abnormal neural activity.

Orofacial neuralgias

Trigeminal neuralgia

Clinical features Trigeminal neuralgia is an excruciating, debilitatingorofacial pain illness largely recognized as one of themost painful human conditions. It is also known by thename tic douloureux owing to the facial expression orwince that often accompanies the painful episode.Trigeminal neuralgia is a rare disorder, with an overallincidence of 3 to 5 persons per 100,000 (and anincreased risk in the elderly where incidence rises two-to threefold to 6 to 12 persons per 100,000). Althoughrare, trigeminal neuralgia assumes a place of promi-nence in dental medicine because many patients withtrigeminal neuralgia believe the pain may be tooth-related and seek inital care from the dentist. The pain isdescribed as stabbing, shooting, electric shock-like painlasting seconds to minutes. Most times the patient isaware of the trigger for pain, such as light touch to anintra- or extraoral region, or facial or tongue move-ment. Thus, trigeminal neuralgia is the quintessentialneuropathic pain, characterized by profound allodynia.The pain often radiates to areas outside the trigger zone.The frequency is variable, from several episodes daily toevery few months; in rare and progressive cases the painmay become continuous. The pain is almost always uni-lateral and occurs nearly equally in the maxillary andmandibular trigeminal divisions, less commonly, in the

O R O F A C I A L N E U R A L G I A S A N D N E U R O P A T H I C P A I N 341

ophthalmic division. Trigeminal neuralgia occurs nearlyequally among males and females, though some reportshave found slightly higher rates among females.

Trigeminal neuralgia may be primary or secondary.Secondary trigeminal neuralgia occurs because of someidentified abnormality, such as an intra- or extracranialtumor or other space-occupying lesion, multiple sclerosis(MS), or trauma. Primary trigeminal neuralgia occurs inthe absence of an identified cause; most cases of trigem-inal neuralgia are primary. Primary trigeminal neuralgiausually occurs in individuals over 50 years of age,whereas secondary trigeminal neuralgia usually occurs inyounger individuals. Thus, the suspicion for an underly-ing illness, such as tumor or multiple sclerosis, isincreased in younger patients with trigeminal neuralgia,and their evaluation must include computerized tomog-raphy (CT) or magnetic resonance imaging (MRI) of thehead and brain to identify related pathology.

EtiologyMost cases of trigeminal neuralgia are primary innature, without an identified underlying cause.Although a universal etiologic theory for trigeminalneuralgia does not exist, there is little disagreement thatit is a neuropathic pain disorder resulting from alteredsensory processing either in the trigeminal ganglion orthe central trigeminal neuraxis. Detection and encodingof the light touch stimulus that provokes the pain isapparently normal at the sensory receptor level, with aloss of modality properties (light touch leading to painsensation) occurring at or proximal to the trigeminalganglion. A commonly accepted but not proven etiologyis the presence of abnormal vascular anatomy, mostcommonly the superior cerebellar artery, which pressesagainst the trigeminal root in the posterior cranial fossa.Neurosurgical correction by microvascular decompres-sion has been widely used for correction of the vascularabnormality. Demyelination has often been suggested asthe underlying pathology that leads to abnormal electri-cal excitability and pain, although sound evidence tosupport this theory is lacking.

Secondary trigeminal neuralgia develops as a resultof an underlying disorder, such as intra- or extracranialtumor or other space-occupying lesion, MS, or trauma.Common intracranial tumors that can cause trigeminalneuralgia include pituitary adenoma, meningioma,glioma, and acoustic neuroma. In such cases, the under-lying disorder presumably leads to ectopic electricalactivity caused by direct pressure or demyelination. It isnot clear, however, why the pain is episodic even thoughthe underlying pathology is constant. Approximately 5to 10% of patients with MS develop trigeminal neural-gia, which may be the initial symptom of undiagnosedMS. Whenever trigeminal neuralgia develops in ayounger individual, the suspicion for underlying disease

should be increased and appropriate diagnostic imagingtests should be ordered.

DiagnosisTrigeminal neuralgia is a clinical diagnosis based almostexclusively on the history and physical examination;imaging studies may further identify underlying disor-ders. Paroxysmal unilateral pain described as sharp,stabbing, or electric-like with pain-free intervals and anidentified trigger are the essential features. The possibil-ity for local somatic disease (ie, odontogenic) should becarefully evaluated, though odontogenic somatic pain isunlikely to be characterized by intermittent episodes ofpain. A complete cranial nerve examination should beperformed, and suspicion for trigeminal neuralgia sec-ondary to tumor, vascular abnormality, or MS shouldbe increased when there are other abnormalities on theneurologic examination. Because the condition is inter-mittent and paroxysmal, the physical examination istypically completely normal. Trigeminal sensory thresh-olds are generally normal and symmetric, except duringa pain episode when there exists profound allodynia.There are generally no signs of somatic or inflammatoryinjury. Diagnostic imaging (CT or MRI) when multiplesclerosis is suspected should be performed for allpatients with trigeminal neuralgia, and especially thosewho develop symptoms before 50 years of age.

Do not treat what has not been diagnosed. Adher-ence to this simple principle avoids the unfortunate butnot uncommon experience of many patients withtrigeminal neuralgia who receive inappropriate treat-ment directed toward an odontogenic source that doesnot exist. Although certainly there are some instances inwhich it is difficult to exclude the possible contributionof coexisting dental disease, bear in mind the funda-mental differences between odontogenic (somatic) andneuropathic pain. If the pain is believed to be caused byan odontogenic disease, then generally speaking thepain will be more constant in nature, respond faithfullyto provocation by mechanical or thermal stimulation,and be localized to the region of presumed pathology. Ifthe pain is caused by trigeminal neuralgia, virtuallynone of those features of somatic pain will exist, ratherthe pain will be intermittent, paroxysmal, and outsidethe trigger or provocation zone.

TreatmentSeveral medical and surgical modalities of treatmentexist for trigeminal neuralgia; all therapies are directedtoward reducing nerve excitability. Medical therapy isthe preferred initial treatment for those who can toler-ate the medications. Membrane-stabilizing medications,such as carbamazepine, gabapentin, valproic acid,phenytoin, and baclofen are commonly used alone or incombination. These medications all act to reduce nerve

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excitability by modulating conductance of ions acrossthe excitable nerve membrane. Medications should beprescribed only by those clinicians experienced withtheir use, since all have side effects and adverse reac-tions, and some require hematologic monitoring. Med-ical treatment provides complete or acceptable levels ofrelief for approximately 75 to 80% of patients. Somepatients enjoy complete remission, and a minority maybecome unresponsive after prolonged medical therapy.Surgical therapies exist for those patients who cannottolerate, become refractory to, or do not respond ini-tially to medical therapy.

An invaluable class of medications for the treatmentof neuropathic pain in general are the tricyclic and het-erocyclic antidepressant drugs, most notably amitripty-line and nortriptyline. These drugs are used alone or incombination with membrane-stabilizer medications, butat doses far below those used to treat clinical depressionor other mood disorders. Although their exact mecha-nism of action for providing relief of neuropathic painis not known, it appears that their modulation of nor-epinephrine neurotransmission at segmental (spinalcord and brain stem) as well as supraspinal levelsreduces neuronal excitability and pain perception. It isclear that these drugs used in the dose range for neuro-pathic pain are not treating a clinical depression orother primary mood disorder.

Minimally invasive treatments for trigeminal neural-gia include percutaneous glycerol or alcohol injection orradiofrequency neurolysis directed toward the affectedtrigeminal division. These neuroablative procedures areperformed by the anesthesiologist or neurosurgeon underfluoroscopic imaging for guidance and generally aim toinactivate, for varying periods of time sensory signalsfrom the trigger zone; a common side effect is variablelevels of anesthesia in the territory supplied by the treatednerve. Most recently, preliminary results using minimallyinvasive stereotactic gamma radiation (“gamma knife”)have demonstrated excellent relief. The percutaneous andstereotactic radiosurgery techniques provide relief forabout 75% of patients, especially those who have failedmedical therapy; these procedures may need to berepeated months to years later if symptoms recur. Finally,microvascular decompression is a cranial neurosurgicalprocedure to reposition an aberrant blood vessel, usuallythe anterior superior cerebellar artery. As a neurosurgicalprocedure, it has the risks of hearing loss, corneal anes-thesia, cerebral embolism, and facial nerve injury, amongothers. However, for patients who have failed otherforms of treatment, it also offers an approximately 75%success rate. Trigeminal neuralgia secondary to intra- orextracranial tumor or attributable to MS is treated byaddressing the underlying disorder. However, manypatients require the additional use of membrane-stabiliz-ing medications or tricyclic or heterocyclic medications.

Glossopharyngeal neuralgia

Clinical featuresGlossopharyngeal neuralgia is a neuropathic pain thatshares many of the features of trigeminal neuralgia,with a few notable exceptions. The pain location is inthe distribution of the glossopharyngeal nerve, specifi-cally the posterior tongue and lateral oropharynx. Thepain is less intense than that of trigeminal neuralgia,though still paroxysmal and episodic in nature, and isprovoked by swallowing or contact with the mucosaoverlying the region innervated by the glossopharyngealnerve. Glossopharyngeal neuralgia is a rare disorder,affecting approximately 0.5 to 1 person per 100,000.

EtiologyGlossopharyngeal neuralgia, more so than trigeminalneuralgia, lacks a unifying etiologic theory. Most recog-nize underlying disease processes similar to those pro-posed for trigeminal neuralgia, namely tumors and vas-cular abnormalities that result in nerve compression andectopic nerve impulses, demyelination, and trauma.

DiagnosisThe diagnosis of glossopharyngeal neuralgia, much thesame as for trigeminal neuralgia, is a clinical diagnosisbased on the history and examination. The possibilityfor an odontogenic source is less likely, owing to theanatomic region involved. A complete cranial nerveexamination is essential for detecting other abnormali-ties that might support an underlying illness, such asMS or a tumor. Computed tomography and MRI areappropriately prescribed to detect related intra- orextracranial disease.

TreatmentGlossopharyngeal neuralgia is responsive to the samemedical therapies used to treat trigeminal neuralgia.Minimally invasive and cranial neurosurgical proceduresare seldom used owing to more limited accessibility tothe glossopharyngeal nerve. As in trigeminal neuralgia,glossopharyngeal neuralgia secondary to intra- orextracranial tumor or attributable to MS is treated byaddressing the underlying disorder. However, manypatients require the additional use of membrane-stabiliz-ing medications or tricyclic or heterocyclic medications.

Postherpetic neuralgia

Clinical featuresUnlike trigeminal and glossopharyngeal neuralgia, post-herpetic neuralgia (PHN) is not a paroxysmal neuro-pathic pain, rather it is a continuous burning or stingingneuropathic pain that persists for more than 3 months inthe distribution of a previous outbreak of herpes zoster,


or shingles. Postherpetic neuralgia shares with otherneuropathic pains the features of hyperalgesia and allo-dynia. Except in the rare case of herpes sine zoster, orzoster reactivation without associated lesions, the vastmajority of patients report an antecedent episode ofshingles. Since herpes zoster, like other human herpesviruses, is a neurotropic DNA virus, it remains dormantin the DNA of primary sensory ganglia following pri-mary infection by varicella zoster (chicken pox). Subse-quent viral reactivation is associated with a painfulvesiculoulcerative rash on the skin or mucosa, corre-sponding to the sensory dermatome of the involvednerve. The condition is usually unilateral, though it maydisseminate by the blood in immunocompromised hosts.Only about 20% of shingles cases affect the trigeminalnerve, involving both intra- and extraoral dermatomes;approximately 80% of cases affect the spinal nerves.

Most cases of herpes zoster affect individuals over 60years of age, with an estimated prevalence as high as24% in that age group. The estimated prevalence of PHNfollowing herpes zoster among patients over 60 years ofage is between 15% and 40%, an approximately 15- to25-fold increased risk compared to patients younger than30 years. Thus, the risk for, and need to prevent PHNincreases significantly with age. Postherpetic neuralgia ismore common among females.

EtiologyFollowing viral reactivation, the herpes zoster virus istransported through the neuronal axoplasm to theperipheral afferent terminals, where its release initiatesan intense inflammatory response resulting in the clini-cal lesion of shingles. During the approximately 2-dayperiod it takes for the virus to travel the distance of thetrigeminal nerve, there is an intense neuritis that may beassociated with a tingling or burning prodrome beforelesions develop. Several reports have demonstrated neu-ronal degeneration of affected primary afferents in thespinal cord, resulting in a loss of primary fibers as wellas degeneration of local and second-order neurons.These degenerative changes are believed to play a majorrole in the establishment of PHN that persists as a neuro-pathic pain long after the zoster lesions have healed.

DiagnosisPostherpetic neuralgia is generally a clinical diagnosisbased on the history and examination, which revealantecedent zoster with burning, hyperalgesia, and allo-dynia in the affected dermatome. Since no virus exists inthe painful region after the zoster lesions have healed,there is little benefit to viral culture or evaluation ofserum antibody titers to herpes zoster.

TreatmentSince PHN occurs most commonly in patients over 60years of age, this age group should receive the most

aggressive treatment at the earliest opportunity. Treat-ment outcome is dramatically improved with early treat-ment: the risk for developing permanent PHN doubleswhen pain persists for more than 6 months. Any patientover 60 years of age who develops shingles should betreated with both antiviral medication (acyclovir, famci-clovir) and a tricyclic antidepressant (amitriptyline, nor-triptyline) to reduce the risk for PHN since preemptivetreatment with a tricyclic antidepressant reduces by 50%the risk of developing PHN. Unfortunately, the dentistrarely has the opportunity to contribute to preemptivetreatment, since patients most often seek care from theirphysician for shingles. Nonetheless, tricyclic antidepres-sant medications should be prescribed as soon as pos-sible during the course of PHN. Corticosteroid medica-tions have also been prescribed during the acute phase ofzoster to reduce neuritis, though its efficacy in prevent-ing PHN has been inconclusive.

Capsaicin cream (0.025% and 0.075%) has beenshown to be an effective topical medication for the reliefof PHN when applied to the painful region. Application2 to 3 times daily of capsaicin depletes substance P, aneuropeptide contained in nociceptive C-fibers thatcontributes to neurogenic inflammation and pain. Ini-tial application of capsaicin may result in a burning sen-sation, but this is diminished after repeated use duringthe first 48 to 72 hours.

Nerve injury and neuroma pain

Clinical featuresNerve injury associated with tissue injury results in acomplex series of bidirectional events between the ner-vous and immune system. Whereas this response isintended to promote healing, it may also result inpathologic events that lead to persistent neuropathicpain. These events may include functional changes inCNS and peripheral sensory processing (neuroplastici-ty) as well as neuroma formation. A neuroma is anincomplete or failed attempt at nerve repair followinginjury to a peripheral nerve, resulting in a disorganizednerve fiber that is focally electrically excitable. Thepathologic sensitization of the injured peripheral nerveor CNS results in both peripheral and CNS hyperex-citability, which are manifest as focal allodynia andmechanical hyperalgesia at the site of injury.

What sets nerve injury and neuroma pain apart fromthe neuralgias is the provocation of pain upon stimula-tion of a discrete region innervated by the injured nerve.Whereas the neuralgias demonstrate episodic pain,pain-free intervals, and periods of normal stimulus-response function between attacks, neuroma and nerveinjury pain most often result in constant allodynia andmechanical hyperalgesia in a discrete zone supplied by

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the injured nerve. Rarely is there a palpable or other-wise detectable mass corresponding to the location of aneuroma. Neuroma pain is usually bright, sharp, andwell localized but may also result in radiating pain sen-sations as well as continuous burning pain that spreadsbeyond the immediate injured region.

EtiologyAlthough knowledge of the full spectrum of events thatcan occur following nerve injury continues to expand ata rapid pace, several relevant events are known at thistime. Within moments of tissue and nerve injury, a com-plex series of neuroimmune events occur that can: (1)sensitize the injured nerve, (2) lead to neurogenic inflam-mation and promote further leakage of proinflammatorymediators from the injured blood vessels, (3) contributeto neuroproliferative events that may contribute to neu-roma formation, and (4) result in functional and pheno-typic changes in primary and second-order neurons suchthat these neurons change their future excitability andresponsiveness. Together, the pathologic events mayresult in CNS neuroplasticity and hyperexcitability thatsustain a neuropathic pain condition. It is not clear whyliterally millions of patients undergo millions of invasiveprocedures every day yet only a small portion developpostprocedure neuropathic pain. Certainly, there aremultiple factors that come to bear, none of which aresufficiently well understood to develop a working the-ory. It is interesting to note that there exist engineeredstrains of mice that predictably respond to nerve injuryby developing painful neuromas. Thus, a genetic factormay contribute as the risk factor.

DiagnosisNerve injury and neuroma pain most often are associ-ated with an identifiable antecedent injury. However,the nature and extent of that injury can vary. Althougha rare event, even minor trauma from periodontal scal-ing, pulp extirpation, and minor incision can potentiallylead to neuropathic pain. There must be a careful searchfor focal mechanical hyperalgesia and allodynia; thiscan be difficult and be associated with an area as smallas 2 mm2. Identification of a reliably sensitive focal areais highly suggestive of a neuroma. A small amount oflocal anesthesia applied to the painful focus eliminatesthe pain and further supports the essentially peripheralnature of the problem. However, persistence of painafter local anesthesia does not exclude the existence ofa neuroma, but may indicate the coexistence of patho-logic neuroplastic changes in the CNS that contribute tothe pain experience.

TreatmentWhen the injury involves a large-caliber nerve (inferioralveolar, lingual) and the precise location of the pre-

sumed neuroma can be reasonably well determined,microsurgical repair is an option. However, such local-ization and involvement of a larger nerve is uncommon,making surgical repair a less effective treatment alterna-tive. Furthermore, nerve injury and neuroma pain thatpersists for a long time (more than 6 mo) is lessamenable to a favorable surgical outcome. Locallyapplied capsaicin cream can be an effective treatmentfor focal nerve injury pain. Use of capsaicin intraorallymay require fabrication of a stent that can keep thecream in contact with the mucosal surface and minimizeleakage throughout the mouth. The cream should bemassaged into the painful area three times daily, thencovered with a stent when possible for approximately20 minutes. Although there exist several reports ofrepeated local anesthetic injection with or without cor-ticosteroid (which has been shown to reduce neuromaexcitability), definitive long-term data are lacking.Likewise, several topical formulations of membrane-stabilizer and N-methyl-D-aspartate (NMDA) antago-nists have been reported in isolated cases and small caseseries, again without definitive long-term data. The useof tricyclic antidepressant medications as neuropathicanalgesics often provides additional relief.

Phantom tooth deafferentation pain

Clinical featuresPhantom tooth pain (PTP) is a condition of persistentpain in the teeth, face, or alveolar process that followspulp extirpation, apicoectomy, or tooth extraction. Sev-eral reports have demonstrated that approximately 3 to4% of patients undergoing endodontic therapy havepersistent, unexplained pain or unpleasant sensations inthe treated tooth. The term phantom tooth pain wasfirst coined in 1978, though the condition has been rec-ognized by different terms for many decades. Thepatient with PTP is the one most likely to have under-gone multiple conventional and surgical endodontictreatments as well as tooth extractions in a continuedattempt to relieve the phantom pain. This also is thepatient most likely to be labeled by the clinician as hav-ing a psychogenic pain. Recognizing the condition as aneuropathic pain rather than a somatic or psychogenicpain should immediately prevent such treatment, sincesomatic pain would not move from one tooth to thenext or persist after the nerve has been amputated.Patients with PTP are often diagnosed incorrectly withatypical facial pain (see Chapter 33).

The patient with PTP usually describes a constantdull, deep, aching pain with occasional spontaneoussharp pain; there is no refractory period. The pain isexperienced in a tooth that is denervated by root canaltherapy or has been extracted. The phantom sensation


is in the missing tooth itself, rather than in the edentu-lous alveolar ridge, which is more accurately describedas an intraoral stump pain. The patient may also expe-rience perverted sensations of tooth size, shape, or loca-tion. As treatment is directed toward the “sympto-matic” tooth, the symptoms often spread or move toadjacent teeth; subsequent treatment of adjacent teethresults in the same pattern of phantom migration. Thereader is advised to recall the discussion of neuropathicpain and the origins of perception, distinct from sensa-tion, in the introductory sections of this chapter.

EtiologyThe etiology of phantom pain in general and certainlyphantom tooth pain in particular is not known. How-ever, many of the features of phantom tooth pain paral-lel the experiences of limb amputees. Phantom pain ingeneral is a well recognized though poorly understoodphenomenon that affects 80% of limb amputees duringthe immediate postoperative and healing period andremains permanently to some lesser degree for themajority of patients. Several theories exist that onlypartly explain some of the phantom pain phenomena,but no unifying theory exists that describes all features.These theories focus on pathologic neuroplasticity inthe CNS as a result of intense nociceptive afferent activ-ity and neural injury following amputation. The sympa-thetic nervous system is believed to play a role in severalfeatures of phantom pain (see Chapter 33).

Pulp amputation, more than tooth extraction, hasbeen shown to result in peripheral neuropathology (neu-roma formation) as well as CNS neuropathology (degen-eration of local and projection neurons in the CNS).Ample experimental evidence exists to demonstrate thatthe sensory map of the periphery can be immediately andpermanently altered following tissue and nerve injury.This central neuroplasticity is the physiologic substrateby which one can understand how sensations and paincan “move” or spread from one area to another. Con-sider the common experience of the genuine perceptionof a swollen lip following anterior maxillary anesthesia.While the perception of a swollen lip is very real, cer-tainly the lip is not swollen; that is, there is no physicalcorrelate of swelling. However, the local anestheticimmediately altered the relative amount of neural activ-ity and led instantly to a change in perception of bodysize and shape. In the same way, nerve injury can lead toaltered nerve activity that results in phantom pain anddysmorphic perceptions that have a very real physio-logic, though not physical, basis.

Perhaps the most provocative theory to explainphantom pain sensations is Melzack’s neuromatrix the-ory. This theory proposes a genetically determined butexperience-dependent neurosignature, a person’s repre-sentation of self somewhere in the brain, which once

established, exists to some degree independent of thecontinued existence of various body parts. This neuro-signature can be accessed to contribute to awareness ofbody size and shape by any number of neural processes,including those that are independent of any peripheralinput. Thus, injury to the nervous system by removal ofa body part does not eliminate awareness of that bodypart, rather it changes whatever neurophysiologicdynamics maintained that awareness in some healthyand accurate form. The undeniable perception of alteredbody size or shape, or pain from a body part that doesnot exist, therefore, becomes a product of altered CNSactivity and how that activity relates to the neurosigna-ture of an individual. Considerable psychophysical andphysiologic experimentation is currently underway toexplore this theory in more detail. There is little doubtthat psychological factors contribute to phantom sensa-tions, but little evidence to suggest that the phantom is aresult of psychological illness.

DiagnosisPhantom pain, although likely initiated by peripheralinjurious events (amputation), is certainly predomi-nantly maintained by CNS processes. The diagnosis ofPTP is a clinical diagnosis based on the history andexamination. The patient with PTP complains of persis-tent deep, dull, aching pain in a denervated tooth or atthe site of an extracted tooth; not uncommonly thepatient may have difficulty identifying the precise tooththat is painful. There may be occasional periods of sharppain. The phantom may emerge days, weeks, months,and even years after the initial injury, making identifica-tion of the antecedent injury potentially difficult. Thereare no associated radiographic abnormalities, and painis not worsened by mechanical or thermal stimulation.The possibility for local odontogenic pain should be con-sidered and careful examination performed to be sure nosomatic source of pain exists (fractured tooth, failed rootcanal therapy). However, the clinician must be cautiousnot to assume an odontogenic source when there is noevidence to support the diagnosis, and should not initi-ate treatment based on that assumption. Althoughpotentially frustrating to both patient and doctor, initi-ating inappropriate treatment based on an unsupporteddiagnosis will not improve the condition and is morelikely to worsen it. As difficult as it may be, offering notreatment is preferable to inappropriate treatment.

TreatmentTreatment of PTP is challenging and generally is basedon local (injection) and oral medications, always com-bined with cognitive therapy and psychological coun-seling. The patient must be reassured that the pain is notimagined and does not represent an undiagnosed seri-ous disorder (ie, cancer). The patient must be educated

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about the nature of the problem so he or she compre-hends how the nervous system itself can lead to suchpainful perceptions.

Medical therapy includes the use of neuropathicpain analgesics, such as tricyclic antidepressant medica-tions (amitriptyline, nortriptyline) and GABA agonists,such as baclofen and clonazepam. Some patients requirefixed daily doses of oral narcotic, though this shouldonly be pursued by clinicians familiar with the addictiveand medical complications of chronic narcotic use. Atrial of the anticonvulsant carbamazepine may beappropriate if other treatment fails. Although it isunlikely to relieve PTP, if the patient does experiencerelief, one should consider the possibility that thepatient suffers from trigeminal neuralgia. A relativelynew anticonvulsant medication, gabapentin, may pro-vide relief for PTP, as it has been found to be effective inother neuropathic deafferentation pain disorders,though no study has examined its use in PTP.

Some authorities recommend the use of repeatedinjection with long-acting local anesthetic (without epi-nephrine) combined with low-dose corticosteroid (dexa-methasone); both have been shown to reduce neuronalexcitability at sites of nerve injury. The success of injec-tion therapy depends on selection of the correct site forinjection. A careful history and examination are essen-tial to precisely identify the location of the phantompain or pains. In addition to sites at the teeth, others areat the terminal points of the trigeminal divisions (ie,supraorbital, infraorbital, nasolabial, mental). Efficacyof repeated injection for PTP awaits well-designed,prospective clinical trial.

Sympathetically maintained pain

Clinical featuresThe role of the sympathetic nervous system in the initia-tion or maintenance of chronic neuropathic pain has beena topic of considerable debate and some confusion; itsrole in orofacial neuropathic pain is understood even less.Adding to the confusion, it has been known by otherterms, such as causalgia and reflex sympathetic dystro-phy. Sympathetically maintained pain (SMP) may be anindependent pain disorder, or a contributing pathologicprocess to other orofacial neuropathic pain, most notablynerve injury and phantom tooth pain. When SMP is amajor component of a neuropathic pain, the featuresinclude constant aching and burning pain with periods ofexacerbation. The pain may at times be accompanied byother signs of sympathetic dysregulation in the affectedregion, such as altered local skin temperature, excessivesweating, and trophic changes, although none of thesesigns is essential in SMP. In all cases where SMP is

involved, there is a history of prior injury. The pain isworsened during periods of physiologic or psychologicalstress and often following injection of a solution contain-ing epinephrine into the painful region.

EtiologyAlthough a single unifying, accepted theory for SMPdoes not exist, several well-developed models provide atheoretic basis for the disorder. In general, it is proposedthat following injury, sympathetic-sensory couplingoccurs in which nociceptors upregulate α-adrenergicreceptors and respond to norepinephrine released fromsympathetic terminals in the injured region. The sympa-thetically generated nociceptor activity produces adynamically maintained state of CNS sensitization andhyperexcitability such that activity in low-thresholdmechanoreceptors, which normally is not painful,results in allodynia and mechanical hyperalgesia.Regional sympathetic blockade interrupts the sympa-thetic-sensory coupling and resets the CNS neurons to adesensitized state, relieving spontaneous pain and allo-dynia. Injection of epinephrine into the affected regionworsens or rekindles the pain.

DiagnosisThe features of SMP are not unique to the condition andare seen in other nonparoxysmal neuropathic pain condi-tions: constant burning, aching, or cramping pain, allo-dynia, and hyperalgesia. However, by definition SMP isabolished when sympathetic activity to the affectedregion is blocked. Thus, the diagnostic test for SMPrequires sympathetic blockade by one of two means: localanesthetic blockade of the stellate ganglion (performedby an anesthesiologist) or intravenous administration ofphentolamine, an α-adrenergic antagonist. Contrary toearly suggestion that signs of autonomic dysfunctionmust be present for a diagnosis of SMP, it is now recog-nized that such signs are not required. That is, the signsof sympathetic dysregulation (altered local skin tempera-ture, excessive sweating, and trophic changes) are disso-ciated from the pain condition. If sympathetic blockade isachieved yet there is no reduction in pain, then the con-dition is a sympathetically independent pain (SIP).

TreatmentTreatment of SMP requires chronic blockade of sympa-thetic activity in the affected region. This is achieved byrepeat stellate ganglion blockade or sympathectomy.Several reports describe the use of clonidine, available ina slow-release patch, for SMP. Clonidine is an agonistfor the presynaptic adrenergic autoreceptor, which thenreduces the presynaptic release of norepinephrine. Sym-pathetic blockade can result in postural hypotensionand bradycardia.


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