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temporallobes.AnnNYAcadSci1998;855:781–786
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12ClinicalDisordersoftheTrigeminalSystem
JohannesFrasnelli,ThomasHummel,DennisShusterman
Introduction
Astherespiratorysystem'ssentinelorgan,thenoseplaysacomplexrole.Similartothemouth—inwhich
flavorisablendoftaste,olfaction,andpiquancy—thenoseintegratesolfactoryand“trigeminal”(irritant)
sensationsintoseamlesspercepts.Thusitisnotunusualtohearastatementsuchas,“Ismelledapungent
odor,”eventhoughtheobserveriscombiningolfactory(cranialnerveI)andtrigeminal(cranialnerveV)
sensationsintheprocess(Fig.12.1). Evaluatingolfactoryandtrigeminalfunctionseparately inclinical
andresearchsettingsischallenging.Appreciatingtheramificationsoftrigeminalfunction—intermsofnot
onlyprimarysensation,butalsomucousmembraneandairwayreflexes—isequallychallenging.
Theobjectiveofthischapteristoprovidethereaderwithanappreciationofnasaltrigeminalanatomy,
physiology, and pathophysiology, including responses to infection, allergy, airborne chemical irritants,
and idiopathic inflammation. To this end, the chapter is organized under the following headings:
Functional Neuroanatomy; Responsiveness to Physical and Chemical Stimuli; and Clinical Disorders.
Whereappropriate,clinicalvignettesandalgorithmshavebeenincludedtoprovidearealisticcontextfor
thematerialdiscussed.
FunctionalNeuroanatomyoftheTrigeminalSystem
PeripheralandCentralAnatomy
Thetrigeminalnerveisthesensorynervethatinnervatestheskinandthemucosaoftheface.
Thetrigeminalnerve(cranialnerveV),withitsthreemajorbranches:ophthalmicnerve(V1),maxillary
nerve (V2), andmandibular nerve (V3), is thelargestcranial nerve,andis primarilya sensory nerve
(with some motor functions).V1andV2together innervate thenasal mucosa;V2 and V3 innervatethe
oral mucosa. From here, they convey both somatosensory and chemosensory information. The three
branchesconvergeonthetrigeminalganglion(Gasserianganglion),wherethecellbodiesoftheincoming
sensoryfibersarelocated.Thisganglionisanalogoustothedorsalrootgangliaofthespinalcord.
From the trigeminal ganglion, neurons project to the trigeminal nucleus (extending from the caudal
medullatotherostralpons)and,aftersynapsingthere,projecttolateral(e.g.,ventrobasal)andmedial
(e.g.,centromedialandparafascicular)thalamicnuclei.Fromhere,neuronsprojecttothesomatosensory
cortex.Inhumans,theV1regionsarerepresentedintheinferiorportionofthepostcentralgyrus,andV3
regionsinmoresuperiorregionsinthecentralsulcus.Inadditiontothesesomatosensorybrainregions,
chemosensory trigeminal stimuli activate brain regions that are commonly considered olfactory and
gustatoryregions,suchastheinsula,theorbitofrontalcortex,andthepiriformcortex.
1
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Fig.12.1Innervationofthenasalcavity.Theolfactorynerveisuniquewithinthecentralnervoussysteminthatitsolfactoryreceptorneurons,
which are in contact withthe external environment, undergo continuous regeneration. The ethmoidandinfraorbital nerves arise fromthe
ophthalmic(first)divisionofthetrigeminal nerve;themaxillarynerve constitutestheseconddivision.Olfactorynervesandolfactorybulbin
yellow(From Hummel T.Olfactoryevokedpotentialsas atooltomeasure progression ofParkinson'sdisease. In: Chase T,BedardP, eds.
FocusonMedicineVol.14—NewDevelopmentsintheDrugTherapyOfParkinson'sDisease.Oxford:BlackwellScience;1999:47–53,with
permission.)
SomaticandAutonomicFunctions
The intranasaltrigeminalsystemactsasa sentineloftheairwaysbymonitoringthenasalmucosal
environment,andisinvolvedindetectingandclearinginhaledharmfulsubstances.
Theintranasaltrigeminalsystemhasseveralfunctions,whichmaybesubdividedintofourcategories.
2
(1)
Neuronsoftheintranasal trigeminalsystemsrelease immediate protective mucosalresponses by axon
response mechanisms.
3
(2) The intranasal trigeminal system provides the afferent connections of
brainstemreflexcircuitssuchascoughing,sneezing,gagging,andvomiting.Thesereflexesalsoinclude
parasympatheticallymediatedsecretions,whicharelocallyactive,andsystemicallyactingsympathetic
vasoconstrictorreflexes.
3
(3)Theintranasaltrigeminalsystemmodulatesbreathingparameters.
4
(4)The
intranasal trigeminal system, together with the olfactory system, monitors inhaled air for quality and
composition.
5
TrigeminalRoleinLocalandRemoteReflexes
Thetrigeminalsystemisinvolvedinlocalandremotereflexes.
The myelinated(Aδ)andunmyelinatedfibersofthe mucousmembranesare responsivetoavariety of
physicalandchemicalstimuli.
6
Stimulationofthesenerves(byheat,cold,touch,andchemicalirritation)
cantriggeravarietyoflocalandremotereflexes.Withinthenasalmucosa,releaseofneuropeptides(e.g.,
substanceP) fromunmyelinatedfibers(the axonreflex)canproducetissueswelling,produceglandular
secretion, and facilitate mast cell degranulation.
7
Central (autonomic) reflexes also participate in the
secretoryresponseintheupperairway.
8
Tissueswellingdecreasesluminalsize,therebyincreasingnasal
airwayresistanceandtheworkofnasalbreathing.Mucosalswellingalsoresultsindecreasedpatencyof
upperairwayostia(i.e.,theEustachiantubesandtheosteomeatalcomplexoftheparanasalsinuses),and
mayplayapartinthepathogenesisofbothotitismediaandsinusitis.
9
In terms of nasal secretory reflexes, so-called gustatory rhinitis—watery rhinorrhea produced by
ingestionofhotor spicyfoods,whichis verycommon inthe population
10
—involves trigeminal nerve
afferentsandfacialnerve(cranialnerveVII)parasympatheticefferents.Dependingupontheindividual,
the strength of the stimulus, and the degree of irritation, this response may also include lacrimation.
Gustatory rhinitis can be blocked by local application of anticholinergic agents (e.g., atropine or
ipratropiumbromide).
11
Bothreflexnasalairflowobstructionandrhinorrheahavebeenpostulatedtoprotectagainstinjurious
inhalants.Inadditiontothesepurelyupperairwayreflexes,avarietyofnasalreflexesisinitiatedinthe
nosebuteffectedatremote sites(Fig.12.2).Coughingandsneezingarethetwobest-knownprotective
reflexestriggeredbyairwayirritation.Bothinvolvethemusculatureofthediaphragmandthoraciccage.
Thesereflexesacttoexpel noxioussubstancesforcefully,thusprotectingthe airway. Lesswell-known
autonomic reflexes originating in the upper airway can be parasympathetic (cardiac slowing,
bronchoconstriction) or sympathetic (epinephrine release from the adrenal medulla, peripheral
vasoconstriction).
12
Despite their protective function, when dysregulated, airway reflexes can become pathological.
Chronic cough,forexample,canarisefrom a varietyofcauses,includingpharmacological (e.g.,ACE
[angiotensin-converting enzyme] inhibitors), inflammatory (e.g., asthma), irritant (postnasal drip;
gastroesophageal reflux disease [GERD]; cigarette smoke), infectious, intrinsic lung disease, and
behavioral factors.
13
An exaggerated cough reflex—defined functionally as a heightened response to
aerosolizedcapsaicin—hasbeentermed“sensoryhyper-reactivity”.
14
Thisdiagnosismaycharacterizea
subsetofpatientswhoself-identify as “chemicallysensitive”andwithimpairedabilitytocope witha
varietyofenvironmentalexposures.
15
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Fig.12.2 Remote reflexes triggeredbynasaltrigeminalstimulation.Trigeminovagal reflexesinclude laryngealadduction andnasobronchial
andreflexbradycardia. (Reproduced withkindpermission from WiddicombeJG. Nasalandpharyngeal reflexes: protective andrespiratory
functions.In:MathewOP,Sant’AmbrogioG,eds.RespiratoryFunctionoftheUpperAirway.NewYork:MarcelDekker;1998:235.)
ResponsivenesstoPhysicalandChemicalStimuli
ReceptiveStructures
The trigeminal system is stimulated via the activation of polymodal nociceptors on free nerve
endingsandsolitarychemoreceptorcells.
Polymodalnociceptors respondtothermalandchemical stimuli.Theirreceptivestructuresarelocated
on free trigeminal nerve endings throughout the oral and nasal mucosa. Compared with the olfactory
nerve,receptordiversitywithinthetrigeminalsystemisrelativelymodest,althoughtheiractivationleads
todiverseperceptionssuchascooling,burning,stinging,ortingling.Withfewexceptions(e.g.,vanillin
and hydrogen sulfide), most volatile substances activate the trigeminal system, especially at higher
concentrations.
5
If volatile substances stimulate boththe olfactory and the trigeminal system, they are
calledmixedolfactory–trigeminalstimuli(e.g.,benzaldehyde,menthol).Atareceptorlevel,chemicaland
thermal stimuli activate specific receptors of the trigeminal nerve, most of which are ion channels
belongingtothesubfamilyoftransientreceptorpotential(TRP)receptors.TheyincludeTRPV1(excited
by capsaicin,
16
eugenol,
17
acids,
18
and heat
16
), TRPM8 (excited by menthol, eucalyptol, and cool
temperatures
19
),andTRPA1(excitedbymustardoil,coldtemperatures,andavarietyofirritantgases
20
).
Thereisalsoevidencefornon-TRPtrigeminalreceptorsactivatedbynicotine
21
andacids.
22
In addition to these receptors on free trigeminal nerve endings, solitary chemoreceptor cells have
beendescribedinthenasalcavity,althoughnotyetinhumans.Thesecellsreachthesurfaceofthenasal
epitheliumandformsynapticcontactswithtrigeminalafferentnervefibers.Theyareactivatedbybitter
substancesviaspecificreceptors.Thesecellsmayaddtotherepertoireofcompoundsthatcanactivate
theintranasaltrigeminalsystem.
23
Thelow-thresholdtrigeminalmechanoreceptorsresponsiblefortheperceptionofmechanicalstimuli
fromthenasalmucosahavenotyet beenidentified.
24
SomeoftheTRP channels mentionedabovemay
serveasmechanoreceptors.
TestingtheIntranasalTrigeminalSystem
The major challenge when testing the intranasal trigeminal system is the intimate connection between
olfactoryandtrigeminalsensorysystems.Mosttrigeminalstimulialsoactivatetheolfactorysystem,
5
and
dosoatlower concentrationsthanthose neededfortrigeminalactivation.Different methods havebeen
developedtoovercomethisproblem,withtheirownadvantagesanddisadvantages.
PsychophysicalTestingMethods
Psychophysical methods to assess the intranasal trigeminal system include testing of anosmic
patients;instructingpatientstofocusontrigeminalratherthanolfactorysensations;orusingmethods
thatdependpurelyorpredominantlyontrigeminalstimulation.
Anosmic patients can only detect mixed olfactory–trigeminal stimuli by virtue of their trigeminal
component.Accordingly,thepercentageofpatientswithanosmiawhodetectastimuluscorrelatestothe
stimulus’trigeminalimpact.
5,25
Aspatientswithanosmiadonotperceiveolfactoryinformation,thesame
methodsusedformeasuringanolfactorythresholdinsubjectswithnormosmiawillresultinatrigeminal
thresholdinsubjectswithanosmia.
26
However,resultsfromanosmicsubjectscannotbegeneralizedtothe
generalpopulation,asanosmiaperseleadstoreducedtrigeminalsensitivity.
27,28
Itis importanttonote
that even though trigeminal thresholds are reduced in anosmic subjects, trigeminal compounds can
nevertheless be perceived. In fact, the difference in trigeminal sensitivity between anosmic and
normosmicsubjectsissmall,andthereforemaynotbedetectedwheninvestigatingonlyasmallnumberof
subjects.However,itisaclearlimitingfactorofthisapproach.
Methods depending on trigeminal stimulation: Some psychophysical tests depend on information
fromthetrigeminalsystem.Themainsuchmethodisthelateralizationtask,inwhichpatientsidentifythe
nostril(i.e.,rightorleft)towhichachemicalstimulusisappliedmonorhinally(i.e.,toonlyonenostril).
This taskis based upon thefactthat humansseemunable tolocalizepureodorants,
29
butcanlocalize
mixedolfactory–trigeminalstimuliwithhighaccuracy.
29–32
Thismethodisabletoestablishthesensitivity
of the trigeminal system (e.g., when comparing the sensory acuity of subject groups,
31,33
or when
comparing the trigeminal potency of different chemical compounds).
26
In clinical testing, a single
concentrationof a test compound thatis a strong trigeminal stimulus (e.g., menthol) may be used in a
semiquantitative screening protocol. The sum of correct identifications is used for further statistical
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analyses. Alternatively, quantitative thresholds forirritant detection canbe generated byemploying an
ascendingconcentrationseriesofthetestchemicalofinterest(Fig.12.3).
Somegroupstakeadvantageofthefactthatthecorneaandconjunctivaoftheeyearealsoinnervated
bythetrigeminalnerveandperceivepainfulsensations,butdonotrespondtopureolfactorystimuli.As
vaporphasechemicalstimulicanevokesensationsofburningorstinginginthecornea,theycanbeusedto
assess trigeminal irritation thresholds in the eye if care is taken to avoid costimulation of the nose.
Interestingly,formanycompounds,irritationthresholdsintheeyeandnosecorrelatesignificantly.
34
Analternativeistousepatientswithnormosmiawhoareinstructedandtrainedtofocusontrigeminal
sensations and to disregard simultaneous olfactorysensations. Typically, subjects receive instructions
suchas,“Haveyoufeltanysensationlikeburning,stinging,cooling,ortickling?”Thismethodallowsfor
theassessmentoftrigeminalperceptionthresholds,
35
butotherapplicationsare alsopossible.Themain
disadvantageofthemethodisthatitcanneverbecompletelydiscountedthatpatientsmaybeinfluenced
bytheolfactoryinput.
Fig.12.3Apparatusforobtainingnasaltrigeminalthresholdsviathelateralizationtechnique.(ImagecourtesyofThomasHummel,MD.)
There is also the possibility to use “pure” trigeminal stimuli (i.e., stimuli that do not produce an
additional chemosensory sensation). However, it is very difficult to exclude a possible concomitant
olfactory stimulation. Possible pure trigeminal stimuli include CO
2
and capsaicin. Of note, the CO
2
concentrationsnecessarytoactasaneffectivetrigeminalstimulusareveryhigh(>100,000ppm).
36
Thus,
CO
2
as a nasal trigeminal stimuluscansafelybe employed onlyas a brief (<3-second)stimulus,or,
alternatively,withmouthbreathingandvelopalatineclosure(i.e.,isolationofthenasalcavity).
NeurophysiologicalMethods
Neurophysiological methodstoassessthe intranasal trigeminalsystemincludethemeasurementof
trigeminalevent-relatedpotentials (ERPs) ornegative mucosal potentials, or nonspecific imaging
techniquessuchasfunctionalmagneticresonanceimagingorpositronemissiontomography(PET).
Trigeminal ERPs are electroencephalography (EEG)-derived polyphasic signals obtained at the
surface of the scalp
37
due to the activation of cortical neurons that generate electromagnetic fields.
TrigeminalERPsarethereforeacentralnervousrepresentationoftheprocessingoftrigeminallymediated
sensations.AstheEEGisanoisysignalthatdetectstheactivityofmanycorticalneuronsaswellasnon-
neuronal activity, ERPs are extractedfrom the random background activity by averaging responses to
singlestimulitoimprovethesignal-to-noiseratio.Toavoideffectsofhabituation,itisnecessarytohave
aninterstimulusintervalofatleast30to40seconds.Thus,ERPrecordingstakealongtime(intherange
of45minuteto2hours),andthepatient'sconcentrationhastobemaintainedbysimpletasks,suchasa
trackingtaskonacomputerscreen.ERPsallowthetrigeminalsystemtobeinvestigatedwiththehighest
temporalresolution(intherangeofmilliseconds).However,spatialresolutionofERPispoor.Recording
ofERPrequires anolfactometer,toensurethestimulushasasharponset, a preciselydefined duration,
and is free from concomitant mechanical or thermal costimulation, all of which are prerequisites for
artifact-freeresponses.
37
ThenomenclatureofthetrigeminalERPresponsesfollowsthatofothersensory
domains:afirstpositivepeak(P1)typicallyoccursatlatencieslaterthan200milliseconds,followedby
a first major negative peak (N1; 400 milliseconds), and the late positive complex (P2/P3; 650
milliseconds).
38
The largest responses are obtained from central andparietal electrodes; measures of
interestareusuallyamplitudesandlatenciesofthemajorpeaks.
Thenegativemucosalpotential(NMP)allowstheperipheryofthetrigeminalsystemtobeassessed.
39
Itisthesummationofthereceptorpotentialsofchemosensitivenociceptorsofthetrigeminalnerve,
40
and
thus is anelectrophysiological correlate of trigeminal activation in thenasal respiratory epithelium,
39
independent of olfactory stimulation. NMPs are recorded by means of an electrode placed on the
respiratorymucosaunderendoscopic control. Usually,fewerrecordingsarerequiredforNMP thanfor
ERP. In fact, one single recording may be enough for a meaningful interpretation. Like ERP, NMP
recordingrequiresanolfactometerforstimuluspresentation.NMPsconsistofaslownegativewavewith
alatencyof~1,000milliseconds.
41
ThelargestNMPs,indicatinghighestsensitivity,areobservedatthe
nasalseptum;thelowest,onthenasalfloor.
42
Functional magnetic resonance imaging (fMRI) measures the ratio of oxygenated
hemoglobin:deoxygenatedhemoglobin,andenables ustoobserve areasofthebrain activatedbyatask
with high spatial resolution (in the millimeter range). fMRI has shown that chemosensory trigeminal
stimulation leads to activation patterns that only partly overlap with somatosensory stimuli (e.g.,
brainstem,thalamus,SI/SII,anteriorcingulate
1
).However,chemosensorytrigeminalstimulialsoactivate
olfactory regions(e.g.,piriform, orbitofrontal, and insular cortex).
1
PET assesses the concentrationof
radioactivemarkersandallowsfordistortion-freeimagingoftheorbitofrontalareasofthebrain,butwith
a weaker spatial and temporal resolution than fMRI. PET-based experiments reported additional
activation in the amygdala, claustrum, and lateral hypothalamus after trigeminal chemosensory
stimulation.
43
Other imaging methods for the investigation of the intranasal trigeminal system include
magnetoencephalographyandnear-infraredspectroscopy.
RelationshipBetweenOlfactoryandNasalTrigeminalStimulation
The olfactory and the trigeminal systems are intimately connected; interactions between the two
sensorysystemstakeplaceonseverallevels.
First, many actions—such as food consumption—lead to the simultaneous stimulation of different
chemosensory systems. When we eat, some substances in the food will activate the olfactorysystem,
othersthe trigeminalsystem. Second,the majorityofodorants,atleastifpresentedatsufficiently high
concentrations,alsoactivatethetrigeminalsystem,andshouldthereforebeconsideredmixedolfactory–
trigeminalstimuli,withfewexceptionstothisrule.
5
Third,ithasbeenshownthatthetrigeminalandthe
olfactorysystemexhibitcentralinteractions.Ifatrigeminalstimulusispresentedsimultaneouslywithan
olfactory stimulus,its intensity is rated higher than ifthe trigeminal stimulus is presentedonits own.
Whensubjectsare,however,focusingonanolfactorystimulus,trigeminalcostimulationhastheopposite
effect.Thisphenomenon was also evident when stimuliwerepresentedtodifferentnostrils, indicating
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central nervous interactions.
44
Multisensory integration centers and orbitofrontal areas
45
have been
suggestedaspotentialsitesforthisinteraction.
DemographicandHealthConditionsAffectingNasalTrigeminalFunction
Age,olfactorydysfunction,anddiseasemayaffectnasaltrigeminalfunction.
Age isthemostprominentdemographicfactortoinfluenceintranasaltrigeminalfunction. Olderpeople
exhibitareducedsensitivityoftheintranasaltrigeminalsystem.ThiscanbeobservedbymeansofNMP,
whichindicatesthatageaffectstheperipheralresponsivenessofthetrigeminalsystem.
46
Thepresenceof
nasal allergies, on the otherhand, appears to confer heightened sensitivity to at least some trigeminal
stimuli.
47
Further,olfactorydysfunctionandotherdiseasesalsoaffecttrigeminalsensitivityasshownby
ERP,NMP,andpsychophysicalmethods.
28
NasalResponsetoAirborneChemicals
Theintranasaltrigeminalsystemreactstomanydifferentindustrialchemicalsandnaturallyoccurring
substances.
Trigeminallymediatedsensory irritationconstitutes the most prominentsymptomcomplexinso-called
sickbuildingsyndrome.
48
Sensoryirritationhasalsobeenmodeledinexperimentalanimals,andprovides
a critical endpoint for many chemical exposure standards.
49
Both reactive chemicals (e.g., chlorine,
formaldehyde) and nonreactive volatile organic compounds are capable of stimulating upper airway
nerves. For several chemicals,irritant thresholdsindifferentareasoftrigeminaldistribution (i.e.,nose
andeye)havebeenshowntobecloselycorrelated.
50
In addition to industrial chemicals, a variety of naturally occurring substances, including capsaicin
(chilipeppers),eugenol(cloves),menthol(mint),allylisothiocyanate(mustardoil),andcinnemaldehyde
(cinnamon),areintentionallyingestedfortheirtrigeminaleffectsintheoralcavity.Thesecompoundsalso
reachthenose,viaeitherinhalationortheretronasalroute.Ofnoteinthiscontext,thesensationofnasal
cooling produced by menthol exposure creates an illusion of nasal airflow patency without actually
affectingnasalairwayresistance.
51
Thus,menthol-containingproductsareoftensoldascoldremediesfor
thesubjectivereliefofnasalblockage,despitetheirlackofobjectivephysiologicaleffect.
Qualitatively,nasalsensationsinducedbytrigeminalstimulationarediverse,andhavebeendescribed
asstinging,burning,tingling,itching,orcooling.Itchingsensationsconveyedbythetrigeminalnerveare
important in the pathophysiology of allergic rhinitis.
52
While a distinction between histamine- and
capsaicin-responsive neurons is well appreciated, much of the remaining neurobiology underlying
qualitativeencodinginthenasaltrigeminalsystemisnotyetunderstood.
53
ClinicalDisordersoftheTrigeminalSystem
EndogenousDisorders
Endogenousdisordersofthetrigeminalsystemincludetrigeminalneuralgiaandmigraine.
Trigeminalneuralgia(ticdouloureux)isachronicpainconditionaffectingthetrigeminalnerve.Thepain
istypicallytriggeredbyactivationofthetrigeminalnerve,whichmayincludesmiling,drinking,talking,
or shaving, leading to strong behavioral consequences. Usually, trigeminal neuralgia starts with mild
symptoms but may become more frequent and more intense over time. Most frequently, trigeminal
neuralgiaaffectswomenolderthan50years.Possiblecausesmayincludecontactbetweenthetrigeminal
nerveandabloodvessel,demyelinatingdisease,suchasmultiplesclerosis,ortumors.Inpatientswith
trigeminalneuralgia,olfactoryandgustatory thresholdshavebeenfoundtobeelevated.However,little
changehasbeennotedinsensitivitytothermal,mechanical,andpainfulstimuli;ifchangeswerefound,
patientsexhibiteddecreasedsensitivity.
54
Migraine can be a debilitating condition characterized by headaches ofvarying severity, typically
accompanied by nausea andphotophobia. While thecause ofmigraine headacheis unknown,themost
common theories relate toa disorder of the serotonergic system, or release of calcitonin gene-related
peptidefromtrigeminalnervefibersinthemeninges.
55
Migraineseemstobeaccompaniedbyinterictal
hypersensitivityofthetrigeminalsystemtopainfulstimulation,
56
whichhasbeeninterpretedastheresult
ofsensitizationinnociceptivepainpathwaysduetofrequentpainexperiences
57
;inaddition,subclinical
pre-attack thermal pain hypersensitivity has been reported.
58
Trigeminal hypersensitivity may also be
connectedtoserotonindepletion.
59
Changesintheolfactorysystemarelessclear.Somestudiesarguefor
an increased olfactory sensitivity
60
; others provide evidence for reduced sensitivity in patients with
migraine.
56
ExogenousDisorders
Exogenousdisordersofthetrigeminalsystemincludeherpeszosterophthalmicus,nasalallergies,the
reactive upper airways dysfunction syndrome, vocal cord dysfunction, respiratory or autonomic
syndromestriggeredbyolfactoryortrigeminalstimulation,andodor-triggeredpanicattacks.
Herpes zoster ophthalmicus represents up to 25% of all cases of herpes zoster (caused by human
herpesvirustype3).Mostpatientspresentwith aperiorbital vesicular rashinthe affecteddermatome.
Some patients may also exhibit ocular effects such as conjunctivitis. Poor nutrition and
immunocompromisedstatus correlatewithoutbreaksofherpes zoster;physical oremotionalstressand
fatiguemayalsoprecipitateanepisode.Toourknowledge,therearenostudiesonintranasaltrigeminal
sensitivityinthiscondition.
Nasal allergies and the trigeminal nerve: Thetrigeminal nerve is likelyto participate inallergies
through various mechanisms, including neurogenic inflammation.
3
Research also indicates that the
trigeminalsystemishyper-reactive inpatientswith allergies, whoaresignificantly moresensitivethan
controlstononallergictriggers,
10
asmeasuredbytrigeminalERP.
61
Further,patientswithnasalallergies
respondmorevigorouslyin termsofnasalcongestiontolowconcentrationsofchlorinegas
62
oracetic
acidvapor.
63
Inadditiontoincreasednasalsensitivity,thenasaltrigeminalsystemisconnectedtoseveral
othersystemsandparticipatesinnumerousreflexes(e.g.,changesinbloodpressureorheartrate,mucus
secretion inthe entire respiratory system, tear secretion, or sneezing).
64
Thus, on multiple levels, the
trigeminal system is involved in nasal allergies. It is currently unclear whether trigeminal sensitivity
couldbeusedtopredictthestatusofanallergicprocessortheefficacyofanantiallergictherapy.
Respiratory or autonomic syndromes triggered by olfactory or trigeminal stimulation: Reflex
rhinorrheaisquitecommonaftereitheringestionofspicyfoodsorinhalationofcoldair.Nasalsymptoms
triggeredbyotherchemicals(e.g.,perfumesandcolognes,cleaningproducts,vehicleexhaust,smoke,and
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