Pan H L, Chen S R, Eisenach J C
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA.
Anesthesiology. 1999 Feb;90(2):509-14. doi: 10.1097/00000542-199902000-00027.
Intrathecally administered clonidine increases release of spinal acetylcholine, which may be related to its analgesic action in neuropathic pain. The current study determined the role of spinal muscarinic and nicotinic receptors in the antiallodynic effect of intrathecally administered clonidine in spinal nerve-ligated rats.
Allodynia was produced in rats by ligation of the left L5-L6 spinal nerves. Mechanical allodynia was determined by application of von Frey filaments to the left hindpaw. The effect of intrathecal injection of saline, two muscarinic receptor antagonists (atropine and scopolamine), and two nicotinic receptor antagonists (mecamylamine and hexamethonium) on the antiallodynic action produced by intrathecal administration of 20 microg clonidine was assessed in six groups of animals. Each group consisted of six to eight rats.
Intrathecal injection of saline or muscarinic or nicotinic receptor antagonists did not alter the withdrawal thresholds. The antiallodynic effect produced by intrathecally administered clonidine was attenuated in a dose-dependent manner by intrathecal treatment with muscarinic and nicotinic antagonists. Although nicotinic receptor antagonists only partially attenuated the effect of clonidine, blockade of spinal muscarinic receptors almost abolished the antiallodynic effect of clonidine.
These results demonstrate that the analgesic effect of intrathecally administered clonidine on neuropathic pain is mediated by spinal muscarinic and nicotinic receptors. Therefore, this study provides functional evidence that spinally released acetylcholine plays a role in the antiallodynic effect of intrathecally administered clonidine in neuropathic pain.
鞘内注射可乐定可增加脊髓乙酰胆碱的释放，这可能与其在神经性疼痛中的镇痛作用有关。本研究确定了脊髓毒蕈碱型和烟碱型受体在鞘内注射可乐定对脊髓神经结扎大鼠抗痛觉过敏作用中的作用。
通过结扎大鼠左侧L5-L6脊髓神经产生痛觉过敏。通过将von Frey细丝施加于左后爪来测定机械性痛觉过敏。在六组动物中评估鞘内注射生理盐水、两种毒蕈碱型受体拮抗剂（阿托品和东莨菪碱）以及两种烟碱型受体拮抗剂（美加明和六甲铵）对鞘内注射20微克可乐定产生的抗痛觉过敏作用的影响。每组由六至八只大鼠组成。
鞘内注射生理盐水或毒蕈碱型或烟碱型受体拮抗剂不会改变撤针阈值。鞘内注射毒蕈碱型和烟碱型拮抗剂可使鞘内注射可乐定产生的抗痛觉过敏作用以剂量依赖性方式减弱。虽然烟碱型受体拮抗剂仅部分减弱可乐定的作用，但阻断脊髓毒蕈碱型受体几乎消除了可乐定的抗痛觉过敏作用。
这些结果表明，鞘内注射可乐定对神经性疼痛的镇痛作用是由脊髓毒蕈碱型和烟碱型受体介导的。因此，本研究提供了功能性证据，表明脊髓释放的乙酰胆碱在鞘内注射可乐定对神经性疼痛的抗痛觉过敏作用中发挥作用。
