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

Systemic administration of sumatriptan and buspirone (20 mg/kg; 5-HT1A agon ists) produced antinociception against acetic acid-induced writhing. The an tinociceptive 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 reserve the sumatriptan- or bu spirone-induced antinociception, but pindolol (10 mg/kg), a nonselective 5- HT1A antagonist, blocked this response. Sumatriptan- or buspirone-induced a ntinociception was significantly potentiated by L-NAME (a nitric oxide [NO] synthase inhibitor) although L-NAME (20 mg/kg) given alone had no effect o n the nociceptive threshold. Recent studies have suggested that the L-argin ine/NO/cGMP pathway is involved in the modulation of pain perception. The p resent results suggest that NO may play a role in cholinergic antinocicepti on-mediated 5-HT1A receptor stimulation and that NO exerts on inhibitory ac tion on cholinergic analgesia. (C) 1999 Prous Science, All rights reserved.