Nitric oxide synthase inhibitors enhance the antinociceptive effects of oxotremorine in mice.

Recent studies suggested that the L-arginine/nitric oxide (NO)/cyclic GMP pathway is involved in the modulation of pain perception. The present experiments were undertaken to find out the role of this pathway in the antinociception induced by oxotremorine administration. Male mice of the CD-1 strain were injected with different doses of the muscarinic agonist oxotremorine (0.005, 0.01, 0.02, 0.03 mg/kg i.p.) 5 min after the administration of saline solution or the inhibitors of NO synthase NG-nitro-L-arginine methyl ester (L-NAME: 10 and 20 mg/kg, i.p.) or NG-nitro-L-arginine (N-ARG: 10 and 20 mg/kg i.p.). Oxotremorine induced a dose- and time-dependent analgesic effect in mice, which was significantly increased by L-NAME and N-ARG administration. Either doses of the NO inhibitors given alone had no effect on the nociceptive threshold. The present results show a role of NO in the antinociception mediated by the muscarinic receptor stimulation and suggest that it exerts an inhibitory action on cholinergic analgesia.