Differences in the mechanism of antinociceptive action of non-steroidal anti-inflammatory drugs in the rat

The purpose of this work was to study the role of nitric oxide (NO) synthesis in the antinociceptive effect of paracetamol, indomethacin and diclofenac in the rat. Although all three drugs induced a significant antinociceptive effect, the mechanism of action did not appear to be the same. N(G)-Nitro-L-arginine (L-NAME), an inhibitor of nitric oxide synthesis, did not significantly modify the effects of paracetamol and indomethacin, whereas it reduced the effect of diclofenac. The effect of L-NAME on diclofenac-induced antinociception was partially reversed by L-arginine. Results suggest differences in the mechanism of action of non-steroidal anti-inflammatory drugs, the L-arginine-NO-cyclic GMP pathway being involved in the antinociceptive effect of some, but not of all the members of the group.