Allosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain

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dc.contributor.authorErgün, D.
dc.contributor.authorJackson, A.
dc.contributor.authorToma, W.
dc.contributor.authorSchulte, M. K.
dc.contributor.authorDamaj, M. I.
dc.contributor.buuauthorBağdaş, Deniz
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi.tr_TR
dc.contributor.scopusid15062425700tr_TR
dc.date.accessioned2023-01-04T05:19:54Z
dc.date.available2023-01-04T05:19:54Z
dc.date.issued2018-01
dc.description.abstractBackgroundNeuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels. The 42 subtype of nAChRs plays an important role in the mediation of pain and several nicotine-evoked responses. Agonists and partial agonists of 42 nAChRs show efficacy in animal pain models. In addition, the antinociceptive properties of nicotine, a non-selective nAChR agonist with a high affinity for 42 nAChRs, is well-known. There is a growing body of evidence pointing to allosteric modulation of nAChRs as an alternative treatment strategy in experimental pain. Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) at 42 nAChRs that enhances agonist responses without activating receptors. We hypothesized that dFBr may enhance nicotine-induced antinociception. MethodsThe present study investigated whether dFBr could attenuate mouse chronic constriction injury (CCI)-induced neuropathic pain by increasing endogenous cholinergic tone or potentiating the nicotine-evoked antiallodynic response. ResultsWe found that subcutaneous administration of dFBr failed to reduce pain behaviour on its own. However, the combination of dFBr with nicotine significantly reversed neuropathic pain behaviour dose- and time-dependently without motor impairment. Our data revealed that this effect was mediated by the 42 nAChRs by using competitive 42 antagonist dihydro--erythroidine. In addition, dFBr failed to potentiate the antiallodynic effect of morphine, which shows the effect of dFBr is unique to 42 nAChRs. ConclusionsThe present results suggest that allosteric modulation of 42 nAChR may provide new strategies in chronic neuropathic pain. Significance42 nAChRs are involved in pain modulation. dFBr, a PAM at 42 nAChRs, potentiates the nicotine response dose-dependently in neuropathic pain. Thus, the present results suggest that allosteric modulation of 42* nAChR may provide new strategies in chronic neuropathic pain.en_US
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA (R01-CA206028)en_US
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) (R01CA206028)en_US
dc.identifier.citationBağdaş, D. vd. (2018). ''Allosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic pain''. European Journal of Pain, 22(1), 84-93.en_US
dc.identifier.endpage93tr_TR
dc.identifier.issn1090-3801
dc.identifier.issn1532-2149
dc.identifier.issue1tr_TR
dc.identifier.pubmed28809075tr_TR
dc.identifier.scopus2-s2.0-85038446102tr_TR
dc.identifier.startpage84tr_TR
dc.identifier.urihttps://doi.org/10.1002/ejp.1092
dc.identifier.urihttps://onlinelibrary.wiley.com/doi/10.1002/ejp.1092
dc.identifier.urihttp://hdl.handle.net/11452/30248
dc.identifier.volume22tr_TR
dc.identifier.wos000418080700009tr_TR
dc.indexed.pubmedPubMeden_US
dc.indexed.scopusScopusen_US
dc.indexed.wosSCIEen_US
dc.language.isoenen_US
dc.publisherBlackwell Publishingen_US
dc.relation.collaborationYurt dışıtr_TR
dc.relation.journalEuropean Journal of Paintr_TR
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAnesthesiologyen_US
dc.subjectNeurosciences & neurologyen_US
dc.subjectDiscriminative-stimulusen_US
dc.subjectAgonisten_US
dc.subjectAbt-594en_US
dc.subjectStoichiometryen_US
dc.subjectSensitivityen_US
dc.subjectAllodyniaen_US
dc.subjectEfficacyen_US
dc.subjectLigandsen_US
dc.subjectBeta-2en_US
dc.subjectNS9283en_US
dc.subject.emtreeBromine derivativeen_US
dc.subject.emtreeDesformylflustrabromineen_US
dc.subject.emtreeMorphineen_US
dc.subject.emtreeNicotineen_US
dc.subject.emtreeNicotinic receptor alpha4beta2en_US
dc.subject.emtreeUnclassified drugen_US
dc.subject.emtreeBrominated hydrocarbonen_US
dc.subject.emtreeDesformylflustrabromineen_US
dc.subject.emtreeIndole alkaloiden_US
dc.subject.emtreeNicotineen_US
dc.subject.emtreeNicotinic agenten_US
dc.subject.emtreeNicotinic receptoren_US
dc.subject.emtreeNicotinic receptor alpha4beta2en_US
dc.subject.emtreeAllodyniaen_US
dc.subject.emtreeAllosterismen_US
dc.subject.emtreeAnimal experimenten_US
dc.subject.emtreeAnimal modelen_US
dc.subject.emtreeAntiallodynic effecten_US
dc.subject.emtreeAntinociceptionen_US
dc.subject.emtreeArticleen_US
dc.subject.emtreeCholinergic activityen_US
dc.subject.emtreeChronic constriction injuryen_US
dc.subject.emtreeConcentration responseen_US
dc.subject.emtreeControlled studyen_US
dc.subject.emtreeDrug activityen_US
dc.subject.emtreeMegadoseen_US
dc.subject.emtreeDrug potentiationen_US
dc.subject.emtreeLocomotionen_US
dc.subject.emtreeLow drug doseen_US
dc.subject.emtreeMaleen_US
dc.subject.emtreeMotor coordinationen_US
dc.subject.emtreeMotor dysfunctionen_US
dc.subject.emtreeMouseen_US
dc.subject.emtreeNeuropathic painen_US
dc.subject.emtreeNonhumanen_US
dc.subject.emtreePriority journalen_US
dc.subject.emtreeRotarod testen_US
dc.subject.emtreeAllosterismen_US
dc.subject.emtreeAnimalen_US
dc.subject.emtreeDisease modelen_US
dc.subject.emtreeDrug effecten_US
dc.subject.emtreeMetabolismen_US
dc.subject.emtreeNeuralgiaen_US
dc.subject.meshAllosteric regulationen_US
dc.subject.meshAnimalsen_US
dc.subject.meshDisease mkodels, animalen_US
dc.subject.meshHydrocarbons, brominateden_US
dc.subject.meshIndole alkaloidsen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshNeuralgiaen_US
dc.subject.meshNicotineen_US
dc.subject.meshNicotinic agonistsen_US
dc.subject.meshReceptors, nicotinicen_US
dc.subject.scopusEpibatidine; Nicotinic Receptors; Mecamylamineen_US
dc.subject.wosAnesthesiologyen_US
dc.subject.wosClinical neurologyen_US
dc.subject.wosNeurosciencesen_US
dc.titleAllosteric modulation of α4β2* nicotinic acetylcholine receptors: Desformylflustrabromine potentiates antiallodynic response of nicotine in a mouse model of neuropathic painen_US
dc.typeArticle
dc.wos.quartileQ2en_US

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