{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T04:25:58Z","timestamp":1768969558038,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":547,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>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 <jats:italic>Bothrops asper<\/jats:italic> snake venom, with structural homology to MMPs, to induce joint hypernociception.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Animals received intra\u2010articular (i.art.) BaP1. Hypernociception was assessed using the rat\u2010knee joint articular incapacitation test. Cell influx, prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>), and TNF\u2010<jats:italic>\u03b1<\/jats:italic> levels were assessed in joint exudates following BaP1 injection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>BaP1 (5 <jats:italic>\u03bc<\/jats:italic>g 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<jats:sub>2<\/jats:sub> and TNF\u2010<jats:italic>\u03b1<\/jats:italic> levels in the joint exudates. Pretreatment with either indomethacin (4\u2003mg.kg<jats:sup>\u22121<\/jats:sup> i.p.) or with an anti\u2010TNF\u2010<jats:italic>\u03b1<\/jats:italic> antiserum (i.art.) significantly inhibited both BaP1\u2010induced joint hypernociception and cell influx. In isolated rat peritoneal macrophages, BaP1 increased cyclooxygenase (COX)\u20102 expression, while not altering that of COX\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>This is the first demonstration that a metalloproteinase promotes joint hypernociception. This effect involves local release of PGE<jats:sub>2<\/jats:sub> and TNF\u2010<jats:italic>\u03b1<\/jats:italic>. BaP1\u2010induced increase in PGE<jats:sub>2<\/jats:sub> is associated to increased COX\u20102 expression in macrophages. Blocking PGE<jats:sub>2<\/jats:sub> or TNF\u2010<jats:italic>\u03b1<\/jats:italic> inhibits BaP1\u2010induced 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\u20102 expression.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2007) <jats:bold>151<\/jats:bold>, 1254\u20131261. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707351\">10.1038\/sj.bjp.0707351<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707351","type":"journal-article","created":{"date-parts":[[2007,6,25]],"date-time":"2007-06-25T12:09:57Z","timestamp":1182773397000},"page":"1254-1261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The snake venom metalloproteinase BaP1 induces joint hypernociception through TNF\u2010<i>\u03b1<\/i> and PGE<sub>2<\/sub>\u2010dependent 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