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dc.creatorFernandes, Cristina Maria
dc.creatorTeixeira, Catarina de Fátima
dc.creatorLeite, A. C. R. M.
dc.creatorGutiérrez, José María
dc.creatorRocha, F.A.C.
dc.date.accessioned2016-12-01T15:33:12Z
dc.date.available2016-12-01T15:33:12Z
dc.date.issued2007-08
dc.identifier.citationhttp://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0707351/abstractes_ES
dc.identifier.issn1476-5381
dc.identifier.urihttp://hdl.handle.net/10669/29340
dc.description.abstractBACKGROUND AND PURPOSE: Matrix metalloproteinases (MMPs) have been implicated in joint tissue destruction in arthritis. However, MMPs have not been assigned a role in joint pain. We investigated the ability of BaP1, a metalloproteinase from Bothrops asper snake venom, with structural homology to MMPs, to induce joint hypernociception. EXPERIMENTAL APPROACH: Animals received intra-articular (i.art.) BaP1. Hypernociception was assessed using the rat-knee joint articular incapacitation test. Cell influx, prostaglandin E(2) (PGE(2)), and TNF-alpha levels were assessed in joint exudates following BaP1 injection. KEY RESULTS: BaP1 (5 microg per joint) provoked hypernociception between 1 and 6 h after i.art. injection. Cell influx, mostly neutrophils, was maximal 3 h after BaP1 i.art. injection. BaP1 also led to increase in PGE(2) and TNF-alpha levels in the joint exudates. Pretreatment with either indomethacin (4 mg.kg(-1) i.p.) or with an anti-TNF-alpha antiserum (i.art.) significantly inhibited both BaP1-induced joint hypernociception and cell influx. In isolated rat peritoneal macrophages, BaP1 increased cyclooxygenase (COX)-2 expression, while not altering that of COX-1. CONCLUSIONS AND IMPLICATIONS: This is the first demonstration that a metalloproteinase promotes joint hypernociception. This effect involves local release of PGE(2) and TNF-alpha. BaP1-induced increase in PGE(2) is associated to increased COX-2 expression in macrophages. Blocking PGE(2) or TNF-alpha inhibits BaP1-induced hypernociception. In addition to unravelling a hitherto unknown mechanism whereby TNF blockade provides analgesia in arthritis, the data show, for the first time that MMPs are involved in inflammatory joint hypernociception and induce COX-2 expression.es_ES
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo//FAPESP/Brasiles_ES
dc.description.sponsorshipUniversidad de Costa Rica//UCR/Costa Ricaes_ES
dc.language.isoen_USes_ES
dc.sourceBritish Journal of Pharmacology; Volumen 151, Número 8. 2007es_ES
dc.subjectMetalloproteinase BaP1es_ES
dc.subjectHyperalgesiaes_ES
dc.subjectSynovial Jointes_ES
dc.subjectArthritises_ES
dc.subjectTNF-αes_ES
dc.subjectProstaglandinses_ES
dc.titleThe snake venom metalloproteinase BaP1 induces joint hypernociception through TNF-α and PGE2-dependent mechanismses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.typeArtículo científicoes_ES
dc.identifier.doi10.1038/sj.bjp.0707351
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES


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