Damaj M I, Meyer E M, Martin B R
Department of Pharmacology and Toxicology, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
Neuropharmacology. 2000 Oct;39(13):2785-91. doi: 10.1016/s0028-3908(00)00139-8.
Nicotinic receptors have been found to play a role in modulating pain transmission in the CNS. Activation of cholinergic pathways by nicotine and nicotinic agonists has been shown to elicit antinociceptive effects in a variety of species and pain tests. The involvement of alpha(7) nicotinic receptors in nicotinic analgesia was assessed after spinal (i.t.) and intraventricular (i.c.v.) administration in mice. Dose-dependent antinociceptive effects were seen with the alpha(7) agonist choline after spinal and supraspinal injection using the tail-flick test. Furthermore, alpha(7) antagonists MLA and alpha-BGTX significantly blocked the effects of choline. Dihydro-beta-erythroidine and mecamylamine failed to block choline-induced antinociception. These results strongly support the involvement of alpha(7) subunits in choline's antinociceptive effects. DMXB and 4-OH-DMXB, partial alpha(7) agonists, failed to elicit a significant antinociceptive effect. However, they blocked choline-induced antinociception in a dose-dependent manner following i.t. injection. This antagonism is probably related to their partial agonistic properties of the alpha(7) receptors. These studies suggest that activation of alpha(7) receptors in the CNS elicits antinociceptive effects in an acute thermal pain model.
已发现烟碱型受体在调节中枢神经系统的疼痛传递中发挥作用。尼古丁和烟碱型激动剂对胆碱能通路的激活已被证明在多种物种和疼痛测试中可引发抗伤害感受作用。在小鼠进行脊髓内（i.t.）和脑室内（i.c.v.）给药后，评估了α(7)烟碱型受体在烟碱镇痛中的作用。使用甩尾试验，在脊髓和脊髓上注射α(7)激动剂胆碱后可见剂量依赖性抗伤害感受作用。此外，α(7)拮抗剂MLA和α-BGTX显著阻断了胆碱的作用。二氢-β-刺桐碱和美加明未能阻断胆碱诱导的抗伤害感受。这些结果有力地支持了α(7)亚基参与胆碱的抗伤害感受作用。部分α(7)激动剂DMXB和4-OH-DMXB未能引发显著的抗伤害感受作用。然而，在脊髓内注射后，它们以剂量依赖性方式阻断了胆碱诱导的抗伤害感受。这种拮抗作用可能与其对α(7)受体的部分激动特性有关。这些研究表明，在急性热痛模型中，中枢神经系统中α(7)受体的激活可引发抗伤害感受作用。
