P34 Mechanisms underlying the protective effect of H2S donors against carrageenan-induced knee joint synovitis and nociception

Controversy exists as to whether H 2 S has a direct protective or deleterious effect on arthritis. Although we have evidence from our previous study that exogenous H 2 S delivered to the knee joint can produce a significant anti-inflammatory and anti-nociceptive effect against carrageenan-induced joint synovitis [1] , the mechanisms involved are unknown. To investigate this, synovitis was induced in Wistar rats (previously treated with Lawesson reagent [LR], a classical H 2 S donor) by intra-articular injection of carrageenan into the knee joint in the presence or absence of treatment with glibenclamide (antagonist at the sulfonylurea receptor 1 (SUR1) regulatory sub-unit of ATP-sensitive K + (K ATP ) channels), capsazepine (transient receptor potential vanilloid 1 antagonist TRPV1), and verapamil (L-type Ca 2+ channel blocker). Both nociceptive and inflammatory parameters were assessed 4 h later. Animal procedures were approved by the local Ethics Committee and injections were performed under isoflurane anaesthesia. As expected, LR significantly attenuated the carrageenan (CGN)-induced nociceptive response of the ipsilateral hindpaw (impaired gait and secondary tactile allodynia) and related inflammatory process. Suppression of CGN-induced synovitis formation by H 2 S donor was not reversed by the blockade of K + (K ATP ), TRPV1 or L-type Ca 2+ channels. However, CGN-induced knee oedema and associated nociception was suppressed by glibenclamide, capsazepine or verapamil alone to the same extent as by LR. Compared with control group, determinants of oxidative stress (e.g. glutathione S-transferase (GST) and glutathione reductase (GR)) in the synovial membrane of rats with synovitis showed no differences among groups. These findings demonstrate that exogenous administration of H 2 S donor Lawesson reagent-induced protective effect against CGN-mediated synovitis and referred allodynia does not seem to require activation of both K ATP channels and L-type Ca 2+ or TRPV1 receptors in rats. Thus, the full details of the mechanisms of action of H 2 S donors in CGN-induced synovitis remain to be elucidated. Financial support : CAPES, CNPq, FAPESP.