Sildenafil increases diclofenac antinociception in the formalin test

The antinociceptive activity of an inhibitor of phosphodiesterase 5, alone or combined with diclofenac, was assessed in the formalin test. Local admin istration of diclofenac produced a significant antinociception in both phas es of the formalin test in female Wistar rats. In contrast, 1-[4-ethoxy-3-( 6.7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [3,4-d]pvrimidin-5-yl)pheny lsulfonyl]-4-methyl piperazine (sildenafil, an inhibitor of phosphodiestera se 5) produced significant antinociception, only during the second phase of the formalin test. Non-effective doses of sildenafil (25-100 mug/paw) sign ificantly increased the antinociceptive effect of an inactive dose of diclo fenac (25 mug) in both phases of the test. The antinociception produced by the drugs alone or the combination was due to a local action, as its admini stration in the contralateral paw was ineffective. Since sildenafil is a po tent and selective inhibitor of phosphodiesterase 5, our results suggest th at this drug produced its antinociceptive activity, and increased that of d iclofenac, probably through the inhibition of cyclic GMP degradation. (C) 2 001 Published by Elsevier Science B.V.