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This study was undertaken to evaluate the ability of endogenous and exogenous H<jats:sub>2<\/jats:sub>S to modulate carrageenan\u2010induced synovitis in the rat knee.<\/jats:p><jats:p><jats:bold>Experimental approach:\u2002<\/jats:bold> Synovitis was induced in Wistar rats by intra\u2010articular injection of carrageenan into the knee joint. Sixty minutes prior to carrageenan injection, the rats were pretreated with indomethacin, an inhibitor of H<jats:sub>2<\/jats:sub>S formation (<jats:sc>dl<\/jats:sc>\u2010propargylglycine) or an H<jats:sub>2<\/jats:sub>S donor [Lawesson's reagent (LR)].<\/jats:p><jats:p><jats:bold>Key results:\u2002<\/jats:bold> Injection of carrageenan evoked knee inflammation, pain as characterized by impaired gait, secondary tactile allodynia of the ipsilateral hindpaw, joint swelling, histological changes, inflammatory cell infiltration, increased synovial myeloperoxidase, protein nitrotyrosine residues, inducible NOS (iNOS) activity and NO production. Pretreatment with LR or indomethacin significantly attenuated the pain responses, and all the inflammatory and biochemical changes, except for the increased iNOS activity, NO production and 3\u2010NT. Propargylglycine pretreatment potentiated synovial iNOS activity (and NO production), and enhanced macrophage infiltration, but had no effect on other inflammatory parameters.<\/jats:p><jats:p><jats:bold>Conclusions and implications:\u2002<\/jats:bold> Whereas exogenous H<jats:sub>2<\/jats:sub>S delivered to the knee joint can produce a significant anti\u2010inflammatory and anti\u2010nociceptive effect, locally produced H<jats:sub>2<\/jats:sub>S exerts little immunomodulatory effect. These data further support the development and use of H<jats:sub>2<\/jats:sub>S donors as potential alternatives (or complementary therapies) to the available anti\u2010inflammatory compounds used for treatment of joint inflammation or relief of its symptoms.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2010.00640.x","type":"journal-article","created":{"date-parts":[[2010,2,5]],"date-time":"2010-02-05T14:19:43Z","timestamp":1265379583000},"page":"1463-1474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan\u2010induced knee joint synovitis in the 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