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dc.contributor.authorDutra, Rafael C.
dc.contributor.authorBento, Allisson F.
dc.contributor.authorLeite, Daniela F. P.
dc.contributor.authorManjavachi, Marianne N.
dc.contributor.authorMarcon, Rodrigo
dc.contributor.authorBicca, Maira Assuncao
dc.contributor.authorPesquero, Joao B. [UNIFESP]
dc.contributor.authorCalixto, Joao B.
dc.date.accessioned2016-01-24T14:31:51Z
dc.date.available2016-01-24T14:31:51Z
dc.date.issued2013-06-01
dc.identifierhttp://dx.doi.org/10.1016/j.nbd.2013.02.007
dc.identifier.citationNeurobiology of Disease. San Diego: Academic Press Inc Elsevier Science, v. 54, p. 82-93, 2013.
dc.identifier.issn0969-9961
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/36396
dc.description.abstractMultiple sclerosis (MS) is a progressive, demyelinating inflammatory disease of the human central nervous system (CNS). While the primary symptoms of MS affect motor function, it is now recognized that chronic pain is a relevant symptom that affects both animals and MS patients. There is evidence that glial cells, such as astrocytes, play an important role in the development and maintenance of chronic pain. Kinins, notably bradykinin (BK) acting through B-1 (B1R) and B-2 (B2R) receptors, play a central role in pain and inflammatory processes. However, it remains unclear whether kinin receptors are involved in neuropathic pain in MS. Here we investigated by genetic and pharmacological approaches the role of kinin receptors in neuropathic pain behaviors induced in the experimental autoimmune encephalomyelitis (EAE) mouse model. Our results showed that gene deletion or antagonism of kinin receptors, especially B1R, significantly inhibited both tactile and thermal hypersensitivity in EAE animals. By contrast, animals with EAE and treated with a B1R selective agonist displayed a significant increase in tactile hypersensitivity. We also observed a marked increase in B1R mRNA and protein level in the mouse spinal cord 14 days after EAE immunization. Blockade of B1R significantly suppressed the levels of mRNAs for IL-17, IFN-gamma, IL-6, CXCL-1/KC, COX-2 and NOS2, as well as glial activation in the spinal cord. of note, the selective B-1 antagonist DALBK consistently prevented IFN-induced up-regulation of TNF-alpha and IL-6 release in astrocyte culture. Finally, both B1R and B2R antagonists significantly inhibited COX-2 and NOS2 expression in primary astrocyte culture. the B1R was co-localized with immunomarker of astrocytes in the spinal cord of EAE-treated animals. the above data constitute convincing experimental evidence indicating that both kinin receptors, especially the B-1 subtype, exert a critical role in the establishment of persistent hypersensitivity observed in the EAE model, an action that seems to involve a central inflammatory process, possibly acting on astrocytes. Thus, B-1 selective antagonists or drugs that reduce kinin release may have the potential to treat neuropathic pain in patients suffering from MS. (C) 2013 Elsevier Inc. All rights reserved.en
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipPrograma de Apoio aos Nucleos de Excelencia (PRONEX) of Brazil
dc.description.sponsorshipFundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC) of Brazil
dc.format.extent82-93
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofNeurobiology of Disease
dc.rightsAcesso restrito
dc.subjectAutoimmunityen
dc.subjectMultiple sclerosisen
dc.subjectEAEen
dc.subjectDemyelinationen
dc.subjectNeuropathic painen
dc.subjectBradykinin B-1 and B-2 receptorsen
dc.titleThe role of kinin B-1 and B-2 receptors in the persistent pain induced by experimental autoimmune encephalomyelitis (EAE) in mice: Evidence for the involvement of astrocytesen
dc.typeArtigo
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institutionUniversidade Federal de Santa Catarina (UFSC)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.description.affiliationUniv Fed Santa Catarina, Lab Autoimunidade & Imunofarmacol, BR-88900000 Ararangua, SC, Brazil
dc.description.affiliationUniv Fed Santa Catarina, Ctr Biol Sci, Dept Pharmacol, BR-88040970 Florianopolis, SC, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, Brazil
dc.identifier.doi10.1016/j.nbd.2013.02.007
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000318052000008


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