The snake venom metalloproteinase BaP1 induces joint hypernociception through TNF-α and PGE2-dependent mechanisms
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| Autores: | , , , , |
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| Formato: | artículo original |
| Fecha de Publicación: | 2007 |
| Descripción: | BACKGROUND 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. |
| País: | Kérwá |
| Institución: | Universidad de Costa Rica |
| Repositorio: | Kérwá |
| OAI Identifier: | oai:kerwa.ucr.ac.cr:10669/29340 |
| Acceso en línea: | http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0707351/abstract https://hdl.handle.net/10669/29340 |
| Palabra clave: | Metalloproteinase BaP1 Hyperalgesia Synovial Joint Arthritis TNF-α Prostaglandins |