Nicorandil inhibits mechanical allodynia induced by paclitaxel by activating opioidergic and serotonergic mechanisms

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dc.creatorMarcela Ísis Morais
dc.creatorMárcio de Matos Coelho
dc.creatorRenes de Resende Machado
dc.creatorFelipe Fernandes Rodrigues
dc.creatorSarah Olivia Alves Mendes da Costa
dc.creatorFranciele Aparecida Goulart
dc.creatorFabio Campos Costa
dc.creatorIvo Souza Ferraz de Melo
dc.creatorPaulo Sérgio de Almeida Augusto
dc.creatorMarcela de Moura Garcia Bini Dutra
dc.creatorÂngelo de Fátima
dc.date.accessioned2024-09-09T19:04:30Z
dc.date.accessioned2025-09-08T23:28:45Z
dc.date.available2024-09-09T19:04:30Z
dc.date.issued2018
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.identifier.doihttps://doi.org/10.1016/j.ejphar.2018.02.014
dc.identifier.issn0014-2999
dc.identifier.urihttps://hdl.handle.net/1843/76034
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofEuropean Journal of Pharmacology
dc.rightsAcesso Restrito
dc.subjectDor
dc.subjectFarmacologia
dc.subjectDor neuropática
dc.subjectNicorandil
dc.subjectPaclitaxel
dc.subjectÁcido nicotínico
dc.subjectDoxorrubicina
dc.subjectNicotinamida
dc.subject.otherPain
dc.subject.otherNeuropathic pain
dc.subject.otherNicorandil
dc.subject.otherPaclitaxel
dc.subject.otherChronic constriction injury
dc.titleNicorandil inhibits mechanical allodynia induced by paclitaxel by activating opioidergic and serotonergic mechanisms
dc.typeArtigo de periódico
local.citation.epage114
local.citation.spage108
local.citation.volume824
local.description.resumoRecently, we demonstrated that nicorandil exhibits activities in models of inflammatory and nociceptive pain. In the present study, we extended this investigation by evaluating the effects of nicorandil in models of neuropathic pain induced by paclitaxel or nerve injury in mice. Four intraperitoneal (i.p.) injections of paclitaxel (2 mg/kg.day, cumulative dose 8 mg/kg) or chronic constriction injury (CCI) of the sciatic nerve induced a long lasting mechanical allodynia. Per os (p.o.) administration of two doses of nicorandil (50, 100 and 150 mg/kg) on the 14th day after the first paclitaxel injection attenuated the mechanical allodynia. Equimolar doses of nicotinamide (86.7 mg/kg, p.o.) or nicotinic acid (87.7 mg/kg, p.o.) were devoid of effect. Mechanical allodynia induced by CCI was also attenuated by p.o. administration of two doses of nicorandil (150 mg/kg) on the 14th day after nerve injury. Nicorandil (50, 100 and 150 mg/kg, p.o.) did not affect motor activity. The antinociceptive activity of nicorandil in the model of mechanical allodynia induced by paclitaxel was partially attenuated by naltrexone (5 and 10 mg/kg, i.p.) or cyproheptadine (5 and 10 mg/kg, i.p.), but not by glibenclamide (20 and 40 mg/kg, p.o.). Concluding, nicorandil exhibits activity in experimental models of neuropathic pain when mechanical allodynia is fully established. Activation of opioidergic and serotonergic pathways mediates the antinociceptive activity of nicorandil. It is unlikely that this activity requires biotransformation to nicotinamide or nicotinic acid. Nicorandil should be further evaluated aiming to identify a new alternative in the pharmacological management of neuropathic pain.
local.identifier.orcidhttps://orcid.org/0000-0001-7732-9988
local.identifier.orcidhttps://orcid.org/0000-0002-1284-1195
local.identifier.orcidhttps://orcid.org/0000-0002-2303-4452
local.identifier.orcidhttps://orcid.org/0000-0002-6572-2771
local.identifier.orcidhttps://orcid.org/0000-0003-2344-5590
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S001429991830089X

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