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

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(ATP) pathway 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(ATP) pathway.