The Spinal Muscarinic M1 Receptors and GABAA Receptors Contribute to the McN-A-343-Induced Antinociceptive Effects During Thermal Stimulation of Mice
The Spinal Muscarinic M1 Receptors and GABAA Receptors Contribute to the McN-A-343-Induced Antinociceptive Effects During Thermal Stimulation of Mice
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DOI：
10.1254/jphs.08226fp
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发表时间：
2008-12-01
影响因子：
3.5
通讯作者：
Takano, Yukio
中科院分区：
文献类型：
--
作者：
Honda, Kenji;Horikawa, Keigo;Takano, Yukio
本研究旨在阐明脊髓M受体如何参与热刺激中的抗伤害性感受效应。鞘内(I.T.)注射毒扁豆碱激动剂MCN-A-343可抑制31.5-63.0nmol剂量依赖性热刺激引起的甩尾反应。这种由MCN-A-343诱导的抗伤害效应被鞘内注射(I.T.)呈剂量依赖性地抑制。注射非选择性M受体拮抗剂阿托品、选择性M M、拮抗剂哌仑西平或M-4拮抗剂hibacine。哌仑西平的抑制作用强于硫马西平。相反，选择性M-2拮抗剂甲氧曲明不能抑制MCN-A-343的抗伤害性作用。此外，肌肉注射可减弱MCN-A-343的抗伤害效应。注射GABA(A)拮抗剂荷包牡丹碱，但不注射GABA(B)拮抗剂CGP35348。这些结果表明，MCN-A-343通过脊髓M受体，并至少部分地通过涉及脊髓GABAA受体的神经元通路，对热刺激产生抗伤害性反应。
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 mariner (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, 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, receptors and, at least in part, through neuronal pathways involving spinal GABAA receptors in mice.