Anti-nociceptive effect of kinin B-1 and B-2 receptor antagonists on peripheral neuropathy induced by paclitaxel in mice

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dc.contributor.authorCosta, Robson
dc.contributor.authorMotta, Emerson M.
dc.contributor.authorDutra, Rafael C.
dc.contributor.authorManjavachi, Marianne N.
dc.contributor.authorBento, Allisson F.
dc.contributor.authorMalinsky, Fernanda R. [UNIFESP]
dc.contributor.authorPesquero, João Bosco [UNIFESP]
dc.contributor.authorCalixto, Joao B.
dc.contributor.institutionUniversidade Federal de Santa Catarina (UFSC)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:17:07Z
dc.date.available2016-01-24T14:17:07Z
dc.date.issued2011-09-01
dc.description.abstractBACKGROUND and PURPOSEIn the current study, we investigated the role of both kinin B-1 and B-2 receptors in peripheral neuropathy induced by the chronic treatment of mice with paclitaxel a widely used chemotherapeutic agent.EXPERIMENTAL APPROACHChemotherapy-evoked hyperalgesia was induced by i.p. injections of paclitaxel (2 mg.kg(-1)) over 5 consecutive days. Mechanical and thermal hyperalgesia were evaluated between 7 and 21 days after the first paclitaxel treatment.KEY RESULTSTreatment with paclitaxel increased both mechanical and thermal hyperalgesia in mice (C57BL/6 and CD1 strains). Kinin receptor deficient mice (B-1, or B-2 receptor knock-out and B1B2 receptor, double knock-out) presented a significant reduction in paclitaxel-induced hypernociceptive responses in comparison to wild-type animals. Treatment of CD1 mice with kinin receptor antagonists (DALBK for B-1 or Hoe 140 for B-2 receptors) significantly inhibited both mechanical and thermal hyperalgesia when tested at 7 and 14 days after the first paclitaxel injection. DALBK and Hoe 140 were also effective against paclitaxel-induced peripheral neuropathy when given intrathecally or i.c.v.. A marked increase in B-1 receptor mRNA was observed in the mouse thalamus, parietal and pre-frontal cortex from 7 days after the first paclitaxel treatment.CONCLUSIONS and IMPLICATIONSKinins acting on both B-1 and B-2 receptors, expressed in spinal and supra-spinal sites, played a crucial role in controlling the hypernociceptive state caused by chronic treatment with paclitaxel.en
dc.description.affiliationUniv Fed Santa Catarina, Dept Pharmacol, Ctr Biol Sci, BR-88049900 Florianopolis, SC, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.sourceWeb of Science
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)
dc.description.sponsorshipFundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC)
dc.format.extent681-693
dc.identifierhttp://dx.doi.org/10.1111/j.1476-5381.2011.01408.x
dc.identifier.citationBritish Journal of Pharmacology. Hoboken: Wiley-Blackwell, v. 164, n. 2B, p. 681-693, 2011.
dc.identifier.doi10.1111/j.1476-5381.2011.01408.x
dc.identifier.issn0007-1188
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33981
dc.identifier.wosWOS:000294367700024
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofBritish Journal of Pharmacology
dc.rightsAcesso aberto
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectneuropathic painen
dc.subjectchemotherapyen
dc.subjectpaclitaxelen
dc.subjectkininen
dc.subjectB-1 receptoren
dc.subjectB-2 receptoren
dc.titleAnti-nociceptive effect of kinin B-1 and B-2 receptor antagonists on peripheral neuropathy induced by paclitaxel in miceen
dc.typeArtigo
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