The Spinal Muscarinic M1 Receptors and GABAA Receptors Contribute to the McN-A-343–Induced Antinociceptive Effects During Thermal Stimulation of Mice

Abstract

The present study was undertaken to clarify how spinal muscarinic receptors are involved in the antinociceptive effects in thermal stimulation. Intrathecal (i.t.) injection of the muscarinic agonist McN-A-343 inhibited the tail-flick response to noxious thermal stimulation in a dose-dependent manner (31.5 – 63.0 nmol). This McN-A-343–induced antinociceptive effect was dose-dependently inhibited by intrathecal (i.t.) injection of a nonselective muscarinic receptor antagonist atropine, the selective muscarinic M1 antagonist pirenzepine, or the M4 antagonist himbacine. The inhibition of pirenzepine was greater than that of himbacine. In contrast, the selective muscarinic M2 antagonist methoctramine did not inhibit the antinociceptive effects of McN-A-343. In addition, the McN-A-343–induced antinociceptive effect was attenuated by i.t. injection of the GABAA antagonist bicuculline, but not by injection of the GABAB antagonist CGP35348. These results suggest that McN-A-343 produces its antinociceptive effect on the response to thermal stimulation via spinal muscarinic M1 receptors and, at least in part, through neuronal pathways involving spinal GABAA receptors in mice. Keywords:: muscarinic M1 receptor, McN-A-343, antinociception, spinal GABAA receptor, spinal cord