The novel role of the spinal muscarinic receptors in pain.

阿片类镇痛剂，如吗啡，被广泛用于治疗中度至重度疼痛。此外，最近的研究结果表明，吗啡并不能完全抑制疼痛，例如与糖尿病神经病变相关的疼痛。正是因为这些问题，联合用药在临床实践中才变得有效。有趣的是，最近的报道表明，脊髓中的胆碱能神经元参与了吗啡的镇痛作用。有报道称，给予毒扁豆碱受体拮抗剂可抑制由腹腔注射吗啡引起的抗伤害性反应。然而，脊髓胆碱能系统在吗啡镇痛效应中的作用尚不清楚，因此，本文旨在阐明脊髓中的M受体是如何参与吗啡在热刺激中的抗伤害效应的。我们的研究表明，Muscari…更多的NIC M3受体参与了福尔马林诱导的伤害性反应，而M1受体参与了机械性伤害性反应。此外，阻断脊髓M受体可减弱I.T.的抗过敏反应。可乐定在周围神经损伤后神经病理性疼痛大鼠模型中的作用。这些结果表明，脊髓胆碱能神经元可能在抗伤害性反应中起重要作用。此外，吗啡诱导的抗伤害性反应可被iT抑制。注射M受体拮抗剂阿托品和M_1受体拮抗剂哌仑西平，呈剂量依赖关系。而M_2受体拮抗剂美索曲明和M_3受体拮抗剂4-DAMP不能抑制吗啡的抗伤害效应。注射(I.T.)在M1激动剂中，MCN-A-343在热刺激中具有密切依赖的抗伤害性效应。此外，I.T.产生的抗伤害性作用。吗啡注射不受M_1拮抗剂的抑制。虽然哌仑西平能抑制侧脑室注射吗啡引起的抗伤害性反应。这些结果提示，吗啡在热刺激中的抗伤害性反应受脊髓M_1受体的调节。较少

Opioid analgesics such as morphine are widely used for the treatment of moderate to severe pain. Furthermore, recent findings show that morphine does not fully suppress pain, such as the pain associated with diabetic neuropathy. It is because of these problems that the combination of medicines has become effective in clinical practice. Interestingly, recent reports have suggested that the cholinergic neurons in the spinal cord form part of the analgesia induced by morphine. It has been reported that the administration of a muscarine receptor antagonist suppresses the antinociceptive effects induced by the intraperitoneal administration of morphine. However, the involvement of the spinal cholinergic system in morphine-induced analgesic effects remains poorly understood.In this grant, therefore, was undertaken to clarify how muscarinic receptors in the spinal cord are involved in antinociceptive effects induced by morphine in thermal stimulation. Our studies demonstrated that the muscari … More nic M3 receptor is involved in formalin-induced nociception, and the M_1 receptor is involved in mechanical-induced nociception. In addition, blockade of spinal muscarinic receptors attenuates the antiallodynic response of the i.t. of clonidine in a rat model of neuropathic pain following peripheral nerve injury. These findings indicate that cholinergic neurons in the spinal cord may be important for antinociception.Furthermore, the morphine-induced antinociceptive effects was inhibited by an i.t. injection of the muscarinic antagonist atropine and the M_1 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 M1 agonist McN-A-343 resulted in close-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 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 receptor in the spinal cord. Less