Department of Pharmacology, Institute of Biological Sciences, UFMG, Belo Horizonte, Brazil.
Pharmacology. 2011;88(1-2):18-25. doi: 10.1159/000328409. Epub 2011 Jul 1.
This study investigated the role of the cholinergic system in the modulation of inflammatory and neuropathic pain. The paw pressure test was used with inflammatory pain induced by intraplantar injection of carrageenan and neuropathic pain induced by sciatic nerve constriction. All drugs were locally administered into the right hindpaw of rats. Neostigmine, an acetylcholinesterase inhibitor (2, 4, 8 or 16 μg), inhibited the inflammatory pain induced by carrageenan (250 μg/paw), but not the hyperalgesia induced by prostaglandin E₂ (2 μg/paw). Neostigmine (8 μg) increased the nociceptive threshold only in the treated paw, suggesting only a local effect. The muscarinic antagonist atropine (150, 300 and 600 μg) caused a reduction in the nociceptive threshold induced by carrageenan (125 μg/paw), but not by prostaglandin E₂ (1 μg/paw). Atropine significantly decreased the nociceptive threshold only in the treated paw. On the other hand, in the presence of neuropathic pain, atropine (300 μg) did not alter the nociceptive threshold induced by constriction of the sciatic nerve. This study suggests that a peripheral endogenous cholinergic system involving muscarinic receptors may be activated during inflammation as a modulatory negative feedback control of inflammatory pain.
本研究探讨了胆碱能系统在调节炎症性和神经性疼痛中的作用。使用足底压力测试来诱导炎症性疼痛（通过足底内注射角叉菜胶）和神经性疼痛（通过坐骨神经结扎）。所有药物均局部给予大鼠右后足。乙酰胆碱酯酶抑制剂新斯的明（2、4、8 或 16μg）抑制了角叉菜胶（250μg/足）诱导的炎症性疼痛，但不抑制前列腺素 E₂（2μg/足）诱导的痛觉过敏。新斯的明（8μg）仅增加了受治疗足的痛觉阈值，表明仅具有局部作用。毒蕈碱拮抗剂阿托品（150、300 和 600μg）降低了角叉菜胶（125μg/足）诱导的痛觉阈值，但不降低前列腺素 E₂（1μg/足）诱导的痛觉阈值。阿托品仅在受治疗的足中显著降低痛觉阈值。另一方面，在存在神经性疼痛的情况下，阿托品（300μg）不会改变坐骨神经结扎引起的痛觉阈值。本研究表明，外周内源性胆碱能系统涉及毒蕈碱受体，可能在炎症期间被激活，作为炎症性疼痛的调节性负反馈控制。
