ThermoTRP channels in pain sexual dimorphism: new insights for drug intervention

Abstract

Chronicpainisamajorburdenforthesocietyandremainsmoreprevalentandsevereinfemales.Thepresenceofchronicpainislinkedtopersistentalterationsintheperipheralandthecentralnervoussystem. Oneof themaintypesofperipheralpaintransducersarethetransient receptorpotential channels (TRP),alsoknownasthermoTRPchannels,whichinterveneintheperceptionofhotandcoldexternal stimuli.Thesechannels,andespeciallyTRPV1,TRPA1andTRPM8,havebeensubjectedtoprofoundinvestigationbecauseoftheirroleasthermosensorsandalsobecauseoftheirimplicationinacuteandchronic pain.Surprisingly, theirsensitivitytoendogenoussignalinghasbeenfarlessstudied.Cumulativeevidencesuggeststhatthefunctionofthesechannelsmaybedifferentlymodulatedinmalesandfemales, inpartthroughsexualhormones,andthiscouldconstituteasignificantcontributortothesexdifferences inchronicpain.Here,wereviewtheexcitingadvancesinthermoTRPpharmacologyformalesandfemales intwoparadigmatictypesofchronicpainwithastrongperipheralcomponent:chronicmigraineand chemotherapy-inducedperipheralneuropathy(CIPN).Thepossibilitiesofperipheraldruggabilityoffered bythesechannelsandthedifferentialexploitationformenandwomenrepresentadevelopmentopportunitythatwill leadtoasignificantincrementofthearmamentariumofanalgesicmedicinesforpersonalizedchronicpaintreatment.