Psychophysical Evaluation of a Sanshool Derivative (Alkylamide) and the Elucidation of Mechanisms Subserving Tingle 英文参考文献.docVIP

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Psychophysical Evaluation of a Sanshool Derivative (Alkylamide) and the Elucidation of Mechanisms Subserving Tingle 英文参考文献.doc

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Psychophysical Evaluation of a Sanshool Derivative (Alkylamide) and the Elucidation of Mechanisms Subserving Tingle 英文参考文献

PsychophysicalEvaluationofaSanshoolDerivative (Alkylamide)andtheElucidationofMechanisms SubservingTingle KellyC.Albin1,2,ChristopherT.Simons1* 1GivaudanFlavorsCorporation,Cincinnati,Ohio,UnitedStatesofAmerica,2SchoolofMedicine,UniversityofCaliforniaSanDiego,SanDiego,California,UnitedStatesof America Abstract Previousstudiesinvestigatedtheneuralandmolecularunderpinningsofthetinglesensationevokedbysanshoolandother natural or synthetic alkylamides. Currently, we sought to characterize the psychophysical properties associated with administrationofthesecompounds.Likeotherchemestheticstimuli,thesynthetictingleanalogisobutylalkylamide(IBA) evoked a sensation that was temporally dynamic. Repeated IBA application at short (30 sec) interstimulus intervals (ISI) resulted in a tingle sensation that increased across trials. Application at longer ISIs (,30 min) resulted in a sensation of decreasedintensityconsistentwithself-desensitization.PriortreatmentwiththeTRPV1orTRPA1agonists,capsaicinand mustard oil did not cross-desensitize the tingle sensation evoked by IBA suggesting that neither TRPV1 nor TRPA1 participateinthetransductionmechanismsub-servingtingle.Whenevaluatedover30-mintimeperiod,lingualIBAevoked a sensation that was described initially as tingling and pungent but after approximately 15 min, as a cooling sensation. Further,wefoundthatthesensationevokedbylingualIBAwaspotentiatedbysimultaneousapplicationofcold(0uC)and cool(21uC)thermalstimulibutwasunaffectedbywarm(33uC)andhot(41uC)temperatures.Finally,totestthehypothesis thatthetinglingsensationissubservedbytheactivationofmechanosensitvefibers,weevaluatedlingualtactilethresholds in the presence and absence of lingual IBA. The presence of IBA significantly raised lingual tactile thresholds, whereas capsaicindidnot,identifyingaroleformechanosensitivefibersinconveyingthetinglesensationevokedbysanshool-like compounds.Collectively,theseresultsshowthatlingualalkylamideevokesacomplexsensationthatistemporallydynamic andconsis