Publication:
(E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation

dc.contributor.authorRabha, Younis
dc.contributor.authorHan-Shen, Tae
dc.contributor.authorOrtells, Marcelo O.
dc.contributor.authorArias, Hugo R.
dc.contributor.authorBağdaş, Deniz
dc.contributor.authorGül, Zülfiye
dc.contributor.buuauthorSevdar, Gülce
dc.contributor.buuauthorCavun, Sinan
dc.contributor.buuauthorGürün, Mine Sibel
dc.contributor.departmentTıp Fakültesi
dc.contributor.departmentSinir Bilimleri ve Nöroloji
dc.contributor.orcid0000-0003-0307-3486
dc.contributor.orcid0000-0001-5050-095X
dc.contributor.researcheridJCN-7924-2023
dc.contributor.researcheridAAC-9702-2019
dc.contributor.researcheridDVX-8040-2022
dc.contributor.scopusid57226240379
dc.contributor.scopusid6507468595
dc.contributor.scopusid55664349700
dc.date.accessioned2024-02-20T07:35:06Z
dc.date.available2024-02-20T07:35:06Z
dc.date.issued2021-07-27
dc.description.abstractClinical intervention of pain is often accompanied by changes in affective behaviors, so both assays of affective and sensorial aspects of nociception play an important role in the development of novel analgesics. Although positive allosteric modulation (PAM) of alpha 7 nicotinic acetylcholine receptors (nAChRs) has been recognized as a novel approach for the relief of sensorial aspects of pain, their effects on affective components of pain remain unclear. Therefore, we investigated whether PAM-4, a highly selective alpha 7-nAChR PAM, attenuates inflammatory and neuropathic pain, as well as the concomitant depressive/anxiety comorbidities. The anti-nociceptive activity of PAM-4 was assessed in mice using the formalin test and chronic constriction injury (CCI)-induced neuropathic pain model. The anxiolytic- and antidepressant-like activity of PAM-4 was evaluated using the marble burying test and forced swimming test. Acute systemic administration of PAM-4 dose-dependently reversed formalin-induced paw licking behavior and CCI-induced mechanical allodynia without development of any motor impairment. PAM-4 reversed the decreased swimming time and number of buried marbles in CCI-treated mice, suggesting that this ligand attenuates chronic pain-induced depression-like behavior and anxiogenic-like effects. The effects of PAM-4 were inhibited by the alpha 7-selective antagonist methyllycaconitine, indicating molecular mechanism mediated by alpha 7-nAChRs. Indeed, electrophysiological recordings showed the PAM-4 enhances human alpha 7 nAChRs with higher potency and efficacy compared to rat alpha 7 nAChRs. These findings suggest that PAM-4 reduces both sensorial and affective behaviors induced by chronic pain in mice by alpha 7-nAChR potentiation. PAM-4 deserves further investigations for the management of chronic painful conditions with comorbidities.
dc.description.sponsorshipOVPR Pilot/Seed Grant (Oklahoma State University Center for Health Sciences)
dc.identifier.citationDeniz, B. vd. (2021). "(E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation". Neurological Research, 43(12), 1056-1068.
dc.identifier.doihttps://doi.org/10.1080/01616412.2021.1949684
dc.identifier.endpage1068
dc.identifier.issn0161-6412
dc.identifier.issn1743-1328
dc.identifier.issue12
dc.identifier.pubmed34281483
dc.identifier.scopus2-s2.0-85110975018
dc.identifier.startpage1056
dc.identifier.urihttps://www.tandfonline.com/doi/full/10.1080/01616412.2021.1949684
dc.identifier.urihttps://hdl.handle.net/11452/39859
dc.identifier.volume43
dc.identifier.wos000675131800001
dc.indexed.scopusScopus
dc.indexed.wosSCIE
dc.language.isoen
dc.publisherTaylor and Francis
dc.relation.collaborationYurt içi
dc.relation.collaborationYurt dışı
dc.relation.collaborationSanayi
dc.relation.journalNeurological Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAlpha 7 nicotinic acetylcholine receptors
dc.subjectPositive allosteric modulator
dc.subjectPam-4
dc.subjectFormalin
dc.subjectChronic constriction injury
dc.subjectNeuropathic pain
dc.subjectElectrophysiology
dc.subjectCigarette-smoking
dc.subjectNegative affect
dc.subjectScreening-test
dc.subjectAnimal-models
dc.subjectMouse models
dc.subjectDepression
dc.subjectAgonist
dc.subject3-Furan2-yl-n-p-tolyl-acrylamide
dc.subjectAnxiety
dc.subjectNeurosciences & neurology
dc.subject.emtreeAcetylcholine
dc.subject.emtreeBicarbonate
dc.subject.emtreeBungarotoxin receptor
dc.subject.emtreeComplementary rna
dc.subject.emtreeDistilled water
dc.subject.emtreeFormaldehyde
dc.subject.emtreeFresh water
dc.subject.emtreeFuran derivative
dc.subject.emtreeGentamicin
dc.subject.emtreeHydrogen
dc.subject.emtreeKetamine
dc.subject.emtreeMethyllycaconitine
dc.subject.emtreePenicillin derivative
dc.subject.emtreeRicinomacrogol
dc.subject.emtreeStreptomycin
dc.subject.emtreeWater
dc.subject.emtreeXylazine
dc.subject.emtreeAcrylamide derivative
dc.subject.emtreeAnalgesic agent
dc.subject.emtreeBungarotoxin receptor
dc.subject.emtreeN-phenylacrylamide
dc.subject.emtreeMino acid sequence
dc.subject.emtreeAnalgesic activity
dc.subject.emtreeAnesthesia
dc.subject.emtreeAnimal experiment
dc.subject.emtreeAnimal model
dc.subject.emtreeAnimal tissue
dc.subject.emtreeAntidepressant activity
dc.subject.emtreeAnxiety
dc.subject.emtreeArticle
dc.subject.emtreeBehavior
dc.subject.emtreeBlood brain barrier
dc.subject.emtreeChronic constriction injury
dc.subject.emtreeChronic pain
dc.subject.emtreeComorbidity
dc.subject.emtreeControlled study
dc.subject.emtreeDepression
dc.subject.emtreeElectrophysiology
dc.subject.emtreeFetal bovine serum
dc.subject.emtreeForced swim test
dc.subject.emtreeHypersensitivity
dc.subject.emtreeİncubation time
dc.subject.emtreeLatent period
dc.subject.emtreeLight dark cycle
dc.subject.emtreeLipophilicity
dc.subject.emtreeLocomotion
dc.subject.emtreeMale
dc.subject.emtreeMarble burying test
dc.subject.emtreeMotor dysfunction
dc.subject.emtreeMouse
dc.subject.emtreeNeuropathic pain
dc.subject.emtreeNociception
dc.subject.emtreeNonhuman
dc.subject.emtreeOocyte
dc.subject.emtreePost hoc analysis
dc.subject.emtreeRigidity
dc.subject.emtreeSciatic nerve
dc.subject.emtreeStopwatch
dc.subject.emtreeTranquilizing activity
dc.subject.emtreeVoltage clamp technique
dc.subject.emtreeVon frey test
dc.subject.emtreeAnimal
dc.subject.emtreeAnimal behavior
dc.subject.emtreeBagg albino mouse
dc.subject.emtreeDrug effect
dc.subject.emtreeMetabolism
dc.subject.emtreeNeuralgia
dc.subject.emtreeNociception
dc.subject.emtreePsychology
dc.subject.meshAcrylamides
dc.subject.meshAlpha7 nicotinic acetylcholine receptor
dc.subject.meshAnalgesics
dc.subject.meshAnimals
dc.subject.meshAnxiety
dc.subject.meshBehavior, animal
dc.subject.meshDepression
dc.subject.meshMale
dc.subject.meshMice
dc.subject.meshMice, inbred balb c
dc.subject.meshNeuralgia
dc.subject.meshNociception
dc.subject.scopusInflammation; Methyllycaconitine; 3-(2,4-Dimethoxybenzylidene)Anabaseine
dc.subject.wosClinical neurology
dc.subject.wosNeurosciences
dc.title(E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation
dc.typeArticle
dc.wos.quartileN/A
dspace.entity.typePublication
local.contributor.departmentTıp Fakültesi/Sinir Bilimleri ve Nöroloji
local.indexed.atPubMed
local.indexed.atWOS
local.indexed.atScopus

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