Role of NO/cGMP/KATP pathway in antinociceptive effect of sildenafil in zymosan writhing response in mice.

Abstract.Objective??Previous studies have found that sildenafil produces antinociception in experimental models. This work was undertaken to determine the participation of the NO/cGMP/K_ATPpathway in the antinociception induced by sildenafil.Methods and results??The antinociceptive effect of sildenafil was determined in the zymosan-induced writhing response in mice. Sildenafil (1?30?mg/kg; i. p.), given 30?min before zymosan (1?mg/animal; i. p.), inhibited the writhing response (5.0 ? 1.3 versus 26.6 ? 2.7; p < 0.001) in a dose-dependent manner. L-NAME (30?mg/kg; s. c.) significantly (p < 0.05) reversed this effect (16.6 ? 3.1 versus 6.4 ? 1.6) and L-arginine (200?mg/kg; i. p.) prevented the L-NAME effect (6.8 ? 0.8 versus 16.6 ? 3.1; p < 0.05). ODQ (0,3?1?mg/kg; i. p.) and glybenclamide (0.3?1?mg/kg; p. o.) pre-treatment significantly (p < 0.01) inhibited the antinociceptive effect of sildenafil (18.0 ? 1.7 versus 2.1 ? 1.0 and 5.5 ? 0.7 versus 1.6+0.7, respectively). Diazoxide (10?mg/kg; s. c) significantly (p < 0.001) abolished the glybenclamide effect (1.6 ? 0.8 versus 14 ? 1.2).Conclusions??The data indicate that the antinociceptive effect of sildenafil is dependent on the activation of the NO/cGMP/ K_ATPpathway. [ABSTRACT FROM AUTHOR]