Traumatic Dysesthesia of the Trigeminal Nerve

Dermot Canavan. B Dent ScPostdoctoral ResidentDepartment of Orofaciai PainSchool of DentislryUniversity of California. Los AngelesLos Angeles, California

Steven B. Graff-Radford. DDSAssistant Research DentistDepartment of Orofacial PainUniversity of California. Los AngelesSchool of Dentistryand DirectorThe Pain CenterCedars Sinai Medical CenterLos Angeles, California

Barton M. Gratt. DDSProfessorSection of Oral RadiologySchool of DentistryUniversity of Califomia. Los AngelesLos Angeles, California

Correspondence to:Dr Steven Grai^-RadfordDepartment of Orofaciai PainSchool of DentistryUniversity of California. Los AngelesCHS 43-009Los Angeles, California 90024

Traumatic injury to the peripheral nerves often results in persistentdiscomfort. Substance P has been tmpUcated as a mediator of painand depletion of this neurotransmitter has been shown to reducepam. Subjects suffering from traumatic dysesthesia of the trigemt-nal nerve were treated with capsaicm, a substance P depleter withsignificant long-term effects. This form of therapy may he usedmdiridtuilly or in combination with other pharmacologie mtervefi-ttons in the treatment of traumatic trigeminal dysesthesia.J OROFACIAL PAIN 1994;S:391-396.

Traumatic injury of peripheral nerves in humans may resuit inpain, dysesthesias, paresthesias, and skeletomotor andautonomie disturbances.' These complaints are often self-

limiting, but in a certain population, pain or discomfort may per-sist. This pain poses a significant clinical management problem.Dysesthesia is usually defined as an unpleasant abnormal sensation,either elicited or spontaneous.' Paresthesia, in contrast, has beendefined as any abnormal sensation, such as burning, prickling, orformication, that is not unpleasant.- Both of these conditions arecommonly associated with in|ury to sensory pathways in either theperipheral or central nervous system. The dysesthesia that accom-panies traumatic injury to peripheral nerves has been attributed todeafferentation and hyperactivity of spinal/central pain transmis-sion neurons.' Minor tissue damage associated with pain, withoutobvious nerve damage, may also lead to the development of theclinical characteristics of a neuropathy.'

Although large afferent fibers may show pathologic changes as aresult of trauma, small unmyelinated fibers are invariably affected.'Traumatized afferent neurons may generate activity through fourpossible mechanisms; (Í) neuroma; (2) neurogenic inflammation;(3) trauma; and (4) sympathetically maintained pain. Abnormalsensations resulting from neural injury are therefore the "conse-quence of disorder of the central control systems that establish thenormal routing and amphfication of sensory signals.'"'

Neurotransmitters are required for the ongoing activation andprocessing of nociception. Depending on the site of injury or themechanism producing the pain, different neurotransmitters havebeen implicated. Substantial evidence exists implicating the neu-ropeptide substance P as one of the transmitters in nociceptivepathways.' It has been proposed that the release of substance Pfrom nociceptors following tissue injury contributes to the spreadof neurogenically mediated hyperalgesia and vasodilatation.Substance P, in combination with compounds released irom dam-

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aged tissues, can further sensitize or activate noci-ceptor afférents. Endogenous neuropeptides, par-ticularly substance P,'*"" have been implicated inthe inflammation and pain of arthritic condi-tions,'-" In the rat model, substance-P-inducedinflammation has been shown to be suppressed bycapsaicin, which appears to deplete substance Preceptors on target tissues. This effect is consideredto be long lasting.''' The principal source of cap-saicin (trans-S-methyl-N-vanillyl-6-nonenamide) iscapsicum, the common pepper plant,"

Recent reports suggested that the depolarizingeffect of capsaicin is selective for C-fiber poly-modal nociceptor afférents and involves opening anonselective cation channel.'" Thus the selectivenature of capsaicin's influence on C-fiber activitysuggests tbat it may be useful in treating pain con-ditions triggered by C-fiber input. The efficacy ofcapsaicin m the management of postmastectomypain syndrome,'' postherpetic neuralgia,'^ clusterheadaches,''' diabetic neuropathy,^" and phantomlimb pain '̂ has been evaluated.

Persistent dysesthesia following neural traumahas been reported as a complication of orthog-nathic surgery, implant placement, third-molarremoval, endodontic therapy, and routine dentalprocedures,--"" The present report describes the useof capsaicin as an adjunctive treatment of postsur-gical sensory disturbance involving the trigeminalnerve. The use of capsaicin was helpful in treatingfacial dysesthesia after trauma as in the three casereports presented.

Case 1

A 70-year-old woman, a retired school teacher,presented with bilateral mandibular stiffness in themental nerve distribution. The stiffness was con-tinuous and associated with pain of moderateintensity. The pam was aggravated by changes intemperature and relieved by ibuprofen. The prob-lem starred after the woman sustained a bilateralfractured mandible in the mental nerve region dur-ing a motor vehicle accident. Initially, a plastic sur-geon reduced the fracture. She was then referred toa dentist who believed that a bone graft was neces-sary before the placement of dentai implants. Thiswas done by an oral surgeon who placed a stabiliz-ing plate on the left side of the mandible. Later,three dental implants were placed to support acomplete mandihular denture. The patient's jawstiffness and pain had continued throughout thistime. Because of the pain, the patient was unableto masticate properly on the right side. She was

referred to The Pain Center, Cedars Sinai MedicalCenter, where a comprehensive clinical evaluationwas carried out. The oral, stomatognathic (tem-poromandibular joint), myofascial, and cervicalscreening examinations were noncontributory.However, the neurologic screening examinationrevealed an area of increased sensitivity to lighttouch bilaterally in tbe mental nerve region whichreproduced tbe complaint. The recommended ther-apy was a tricyclic antidepressant in combinationwith a topical capsaicin (Zostrix), Desipraminehydrochloride was started at 10 mg at bedtime andthen gradually increased to 30 mg. It was initiallysuggested that the patient should apply the cap-saicin cream five times a day in the affected areafor 7 days, then three times a day for an additional3 weeks. A topical anesthetic was offered in com-bination with the capsaicin to enhance compliance.At 1-year follow-up, the patient reported no painand continued with 10 mg of nortriptyline hydro-chloride and a single use of capsaicin per day.

Case 2

A é2-year-old woman, a homemaker, presentedwith bilateral continuous pain in her chin and jaw.The pain was variable in intensity, and at times shehad a tingling tightness or burning sensation in herchin. The discomfort had hecn present for 2 yearsfollowing surgery for mandibular advancementand mandibular osteotomy. No aggravating fac-tors were described. Aspirin, ice, and heat hadbeen tried with little benefit. She was referred toThe Pain Center, Cedars Sinai Medical Center,where a comprehensive chnical evaluation was car-ried out. The oral, stomatognathic (temporo-mandibular joint), myofascial, and cervical screen-ing examinations were noncontributory. Theneurologic screening examination of cranial nervesII to Xil was noted to be within normal limits,with the exception of a decreased reaction to pinprick by approximately 20% in the V3 (mandibu-lar) distribution of the trigeminal nerve. Thisdecreased reaction to pin prick was restricted tothe mental nerve distribution bilaterally. An areaof increased reactivity to light touch was noted inthe left mental nerve distribution and along theright border of tbe lower lip. The treatment recom-mended was capsaicin (Zostrix) applied topicallyon the affected site, five times a day for 1 week,and three times a day thereafter. In addition, thepatient was placed on a low dose of desipraminehydrochloride to enhance pain relief. At 6-monthfollow-up, the patient had no pain and continued

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to use 10 mg of desipramine hydroch!oride andcapsaicin daily.

Case 3

A retired man, aged 67 years, presented with abilateral continuous dull aching pain in the preau-ricular region. This pain e?itended to the inferiorhalf of each ear. The patient also complained ofcontinuous tenderness behind the upper half of theright ear. The condition had a sudden onset fol-lowing face-lift surgery 18 months previously. Apostoperative infection in the left preauricular areahad complicated the surgery. No treatment hadbeen provided for his continuing discomfort.Shaving in the affected areas elicited a burning,sringing sensation. Mastication or touching theside of his face also exacerbated his discomfort.The patient's sleep was disturbed because of theresultant discomfort from the pillow touching hisface (hyperesthesia); nothing reportedly alleviatedthe pain. At the UCLA Pain Management Genter,School of Dentistry, clinical findings revealed nor-mal inrraoral, stomatognarhic (temporomandibu-iar joint), myofascial, and cervical screening.Although an active trigger point was detected inthe left masseter muscle, on palparion it failed toreproduce the patienr's chief complaint. The cra-nial nerve screening examination identified a hilar-eral preauricular zone that was hypersensitive rohorh light touch and pin prick. The trearment rec-ommended was to use capsaicin (Zosrrix) cream inthe affected areas five times a day for 1 week andthen three times a day thereafter. Desipraminehydrochloride was prescribed to enhance bothpain relief and sleep.

At 1-week follow-up, the burning qualiry haddisappeared completely, and the parient's sleephad improved significantly. The maximum dose ofdesipramine hydrochloride was 30 mg. At 3-month follow-up, the patient no longer used thecapsaicin because he had developed skin irritationin the region of application. In addition, thepatient no longer used desipramine hydrochloride.

As part of an ongoing facial thermography studyat the UCLA Medical Center, all three patientsreceived investigational facial thermograms usingan Agema 870 Thermovision unit (Secaus, NY)at 0.5°C and 1.0°C imaging sensitivity (0.1"Caccuracy). All three patients displayed asymmetriclateral facial thermograms. Initially, the facial tem-perature (due ro vascular heat emission) in theregion of pain was increased, being asymmetricfrom side to side and rated as "hot" in the affected

region. The pretreatment AT values (area tempera-ture differences from side ro side) ranged from+0.7''C to + l . r G . Posttreatment thermograms,which were also obtained from all three patients,demonstrated decreased heat emission foiiowingcessation ofthe pain. In the affected regions oftheface, AT values ranged from .*- 0.2°C to +0.4°C. Allthree patients had been instructed not ro use cap-saicin for 24 hours prior to their thermographyexaminations. Figure 1 is an example of a pretreat-menr lateral facial thermogram demonstrating a"hot" area (3 cm x 3 cm, yellow area with red ring)over the left cheek of the face. This area was mea-sured and found to have increased vascular heatemission, judged as being "hot." Figure 2 is anexample of a postrreatment lateral facial thermo-gram demonstrating a "warm" area (1 cm x 0.7 cm,yellow spot with red ring) over the same left cheekarea of the face. This area was measured andfound to have less increased vascular hear emissionand was judged as being "warm." The thermo-graphie examinations were comfortable for thepatient and easy to perform, and all threepatients en¡oyed viewing their own thermalimages.

Discussion

This presentation described three cases of traumat-ic neuralgia rhar responded to combinations ofantidepressants and topical capsaicin. Althoughthere was no control and a combined therapy wasused, this combination is believed ro be more effec-tive for neuropathic orofacial pain than rhe use ofeither of these agents independently. Althoughmany other therapies that may have been usefulfor rhis patient population exist, it is suggestedthat the first line of treatment include a tricyclicantidepressant in combination with topical cap-saicin. If this treatment fails, it may be useful roconsider membrane-stabilizing medicarions such ascarbamazepine, haclofen, phenyroin, mexiletine, oreven cionazepam. If the pain is localized intraoral-ly, topical anesthetics may be delivered via a neu-rosensory shield (stenr) in combination with oralmedications.'' Consideration must be given duringthe work-up to sympathetically maintained pain.Should the pain be eliminated by sympathetichlock (stellate block), repeated blockade combinedwith anridepressants or membrane-stabilizing med-ications may be useful.

Often the question arises whether the antidepres-sants are effective secondary to their antidepressantproperties, their effect on sleep, or rhrough anal-

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Fig 1 Pretreatment thermogram of subject 1. Noteelevated temperature ¡yellow area with ted ring) in mid-face area.

Fig 2 Posttreatment thermogram of subject 1. Notereduction of "hor" area (yellovJ area with red ring) itimid-face area.

gesic properties. It is generally accepted that theeffect is independent of antidepressant effects; aslower doses are required, rhe titne to onser is morerapid, and the majority of the pain patients are notdepressed. Sleep is usually considered to be dis-turbed secotidary to the pain, and in itself, mayresult in lowered pain threshold. There is no con-clusive evidence tbat one antidepressant is superiorto another. Therefore, clinical experience must beused to weigh the therapeutic benefits versus thepatient's tolerance of side effects. A cautious reviewof the patient's previous and current medical his-tory is required to identify conditions, such asarrhythmia and epilepsy, that contraindícate theuse of tricyclics. Accommodation to some of themore bothersome side effects, such as dry mouth orsedation, can occur if the medication is prescribedinitially in small incremental doses. Other sideeffects (eg, weight gain) may be unacceptable to tbepatient and require consideration of an alternativemedication. Intolerance to side effects sbould notbe confused with lack of efficacy of the medication,and under these conditions, a similar medicationwithin the same group may be tried. When efficacyis truly in doubt, a medication from a differentclass of anti de pressants should be prescribed. It issuggested that the first choice should be drugs thathave low anticholinergic properties, such asdesipramine hydrochloride or nortriptyline hy-drochloride. Blood levels of these medications arealso sometimes helpful in patients who are notresponding to treatment. It has been observed that

metabolism of the drug is variable and high dosesmay render a subtherapeutic level.

Tbe initial application of capsaicin to skincauses C-fiber activation and pain; bowever,repeated application causes desensitization andhypalgesia. Despite the large amount of experi-mental work done with capsaicin, the exact mech-anism of pain remains uncertain. Most studieshave used capsaicin that was systematicallyapplied to nerve trunks or directly injected into tis-sues. In the few studies that have used topicallyapplied capsaicin, the concentrations were manytimes higher than those used clinically." Severalimportant issues associated with the use of cap-saicin need to be clarified. Substance P is not selec-tively depleted by capsaicin. Marked reductions inthe levels of a number of otber peptides (includingcalcitomn gene-related peptide, somatostatin andvasoactive intestinal peptide) bave also beenfound.'" Rat studies have identified toxic anddegenerative changes in neurons following expo-sure to capsaicin.-'-" If capsaicin does reduce sub-stance P levels by causing C-fiber degeneration, thelong-term effect of this, in humans, needs to beevaluated. Capsaicin application on neurons hasdiffuse effects, and its pain-relieving effects areunlikely to be solely because of reduction of sub-stance P levels. Until the exact mechanism of cap-saicin is understood, chnicians sbould give carefulconsideration to its long-term use. However, thesignificant pain reduction resulting from the topi-cal application of capsaicin, in certain types of

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neurogenically mediated pain conditions, warrantsthe continued clinical study of capsaicin as ananalgesic/pain-modulating substance.

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Resumen

Disestesia traumática del nervio trigérnino

Las lesiones traumáticas de ios nervios periféricos a menudotraen como consecuencia una moleslia persistente. Se ha impl¡.cado que la substancia P es un mediador del dolor, y cuandoeste neurotrarsmisor disminuye, se produce una reducción deldolor En este estudio, personas que sufrían de disestesiatraumática del nervio trigémino fueron tratadas con capsaiclna.la cual reduce la presencia de la substancia P, con efectos alargo plazo. Este tipo de terapia puede ser utilizada individual,mente o en combinación con otras intervenciones farmacológi-cas en el tratamiento de ia disestesia traumática dei nerviotrigémino.

Zusammenfassung

Traumatische Dysästhesie des N. trigeminus

Traumatische Verletzungen der peripheren Nerven resultierenoft Ir bleibenden Beschwerden. Substanz P ist alsSchmerzvermitder darnit in Zusammenhang gebracht worden.Die Erschöpfung dieses Neurotransmitters hat eineSchmerzreduktion zur Folge. Personen, weiche an einer trauma,tischen Dysästhesie des N. trigeminus leiden, wurden mitCapsaicin behandeit, welches über längere Zeit zur Erschöpfurgder Substanz P führt. Diese Form der Therapie kann individuelloder in Kombination mit anderen pharmai^ologischenInterventionen bei der Behandlung von traumatischerDysästhesie des N. trigeminus verwendet werden.

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