The spinal muscarinic M(1) receptors and GABA(A) receptors contribute to the McN-A-343-induced antinociceptive effects during thermal stimulation of mice.
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 M(1) antagonist pirenzepine, or the M(4) antagonist himbacine. The inhibition of pirenzepine was greater than that of himbacine. In contrast, the selective muscarinic M(2) 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 GABA(A) antagonist bicuculline, but not by injection of the GABA(B) antagonist CGP35348. These results suggest that McN-A-343 produces its antinociceptive effect on the response to thermal stimulation via spinal muscarinic M(1) receptors and, at least in part, through neuronal pathways involving spinal GABA(A) receptors in mice.
Honda
Kenji
K
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan. khonda@fukuoka-u.ac.jp
Horikawa
Keigo
K
Ando
Suguru
S
Koga
Kohei
K
Kawata
Satoshi
S
Migita
Keisuke
K
Takano
Yukio
Y
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D043643:Receptor, Muscarinic M1 / Q000819:agonists* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D000700:Analgesics; D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1; D011963:Receptors, GABA-A; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride