L-NAME, a nitric oxide synthase inhibitor, modulates cholinergic antinociception

Systemic administration of sumatriptan and buspirone (20 mg/kg: 5-HT1A agonists) produced antinociception against acetic acid-induced writhing. The antinociceptive effect was potentiated by cholinomimetic physostigmine (0.05 mg/kg i.p.) and blocked by the muscarinic antagonist atropine (5 mg/kg i.p.). Naloxone, an opiate antagonist, failed to reverse the sumatriptan- or buspirone-induced antinociception, but pindolol (10 mg/kg), a nonselective 5-HT1A antagonist, blocked this response. Sumatriptan- or buspirone-induced antinociception was significantly potentiated by L-NAME (a nitric oxide [NO] synthase inhibitor) although L-NAME (20 mg/kg) given alone had no effect on the nociceptive threshold. Recent studies have suggested that the L-arginine/NO/cGMP pathway is involved in the modulation of pain perception. The present results suggest that NO may play a role in cholinergic antinociception-mediated 5-HT1A receptor stimulation and that NO exerts an inhibitory action on cholinergic analgesia.