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The novel role of the spinal muscarinic receptors in pain.

脊髓毒蕈碱受体在疼痛中的新作用。

基本信息

批准号：
14572170
负责人：
TAKANO Yukio
金额：
$ 2.24万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

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

吗啡等阿片类镇痛药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。正是由于这些问题，药物组合在临床实践中变得有效。有趣的是，最近的报告表明脊髓中的胆碱能神经元构成吗啡诱导的镇痛作用的一部分。据报道，给予毒蕈碱受体拮抗剂可抑制由腹膜内给予吗啡引起的镇痛作用。然而，脊髓胆碱能系统在吗啡引起的镇痛作用中的参与仍然知之甚少。因此，在这项资助中，我们的目的是阐明脊髓中的毒蕈碱受体如何参与吗啡在热刺激中引起的镇痛作用。我们的研究表明，穆斯卡里 nic M3 受体参与福尔马林诱发的伤害感受，M_1 受体参与机械诱发的伤害感受。此外，脊髓毒蕈碱受体的阻断会减弱 i.t. 的抗异常疼痛反应。可乐定在周围神经损伤后神经性疼痛大鼠模型中的作用。这些发现表明脊髓中的胆碱能神经元可能对于镇痛作用很重要。此外，吗啡诱导的镇痛作用被 i.t. 抑制。以剂量依赖性方式注射毒蕈碱拮抗剂阿托品和M_1拮抗剂哌仑西平。相反，M_2拮抗剂甲氧曲明和M_3拮抗剂4-DAMP不抑制吗啡诱导的镇痛作用。注射 (i.t.) M1 激动剂 McN-A-343 可在热刺激中产生紧密依赖性的镇痛作用。此外，i.t. 诱导的抗伤害作用。 M_1拮抗剂不抑制吗啡注射。哌仑西平，尽管哌仑西平确实抑制脑室内 (i.c.v) 注射吗啡引起的镇痛作用。这些结果表明吗啡在热刺激中诱导的镇痛作用是由脊髓中的 M_1 受体调节的。较少的