The spinal muscarinic receptor subtypes contribute to the morphine-induced antinociceptive effects in thermal stimulation in mice.

The present study was undertaken to clarify how spinal muscarinic receptors can be involved in the antinociceptive effects induced by morphine in thermal stimulation. The morphine-induced antinociceptive effects (26.6 micromol/kg, s.c.) was inhibited by an intrathecal (i.t.) injection of the muscarinic antagonist (M) atropine and the M(1)/M(4) antagonist pirenzepine in a dose-dependent manner. In contrast, the M(2) antagonist methoctramine and the M(3) antagonist 4-DAMP did not inhibit the morphine-induced antinociceptive effects. Injection (i.t.) of the putative M(1) agonist McN-A-343 resulted in dose-dependent antinociceptive effects in thermal stimuli. In addition, antinociceptive effects induced by the i.t. injection of morphine were not inhibited by the M(1)/M(4) antagonist pirenzepine, although pirenzepine did inhibit the intracerebroventricular (i.c.v.) injection of morphine-induced antinociceptive effects. These results suggest that the morphine-induced antinociceptive effects in thermal stimuli are regulated by the M(1) or M(4) receptor in the spinal cord.