Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents
Evidence for the tonic inhibition of spinal pain by nicotinic cholinergic transmission through primary afferents
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DOI：
10.1186/1744-8069-3-41
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发表时间：
2007-12-19
期刊：
影响因子：
3.3
通讯作者：
Ueda, Hiroshi
中科院分区：
文献类型：
--
作者：
Matsumoto, Misaki;Xie, Weijiao;Ueda, Hiroshi
背景：我们提出神经损伤特异性脊髓强直性胆碱能抑制丧失可能在烟碱乙酰胆碱受体（nAChR）激动剂对神经性疼痛的镇痛作用中起作用。然而，强直性胆碱能对疼痛的抑制作用仍有待进一步研究。结果：本研究发现，胆碱乙酰转移酶（ChAT）信号不仅定位于脊髓外背角纤维（I-III层）和运动神经元，还定位于脊髓背根神经节（DRG）的绝大多数神经元。当用反义寡脱氧核苷酸（AS-ODN）治疗小鼠时，可以减少背角和DRG中的ChAT信号，但不影响运动神经元，它们在爪压和热爪退出测试中表现出显著降低的伤害阈值。此外，在一种新的电刺激诱导的爪脱断（EPW）试验中，as - odn预处理均降低了C-、a- δ和a- β纤维的刺激阈值。在机械、热和EPW试验中，给药尼古丁（10 nmol i.t）诱导损伤阈值的恢复，由AS-ODN降低。然而，在所有这些伤害感觉测试中，尼古丁对对照小鼠或错配混乱(MS)-ODN治疗没有影响。结论：原发性传入胆碱能神经元通过激活nAChR对脊柱疼痛产生强直性抑制，鞘内给药尼古丁可恢复强直性胆碱能抑制的丧失。
Background: We have proposed that nerve injury-specific loss of spinal tonic cholinergic inhibition may play a role in the analgesic effects of nicotinic acetylcholine receptor (nAChR) agonists on neuropathic pain. However, the tonic cholinergic inhibition of pain remains to be well characterized.Results: Here, we show that choline acetyltransferase (ChAT) signals were localized not only in outer dorsal horn fibers (lamina I-III) and motor neurons in the spinal cord, but also in the vast majority of neurons in the dorsal root ganglion (DRG). When mice were treated with an antisense oligodeoxynucleotide (AS-ODN) against ChAT, which decreased ChAT signals in the dorsal horn and DRG, but not in motor neurons, they showed a significant decrease in nociceptive thresholds in paw pressure and thermal paw withdrawal tests. Furthermore, in a novel electrical stimulation-induced paw withdrawal (EPW) test, the thresholds for stimulation through C-, A delta-and A beta-fibers were all decreased by AS-ODN-pretreatments. The administration of nicotine (10 nmol i.t.) induced a recovery of the nociceptive thresholds, decreased by the AS-ODN, in the mechanical, thermal and EPW tests. However, nicotine had no effects in control mice or treated with a mismatch scramble (MS)-ODN in all of these nociception tests.Conclusion: These findings suggest that primary afferent cholinergic neurons produce tonic inhibition of spinal pain through nAChR activation, and that intrathecal administration of nicotine rescues the loss of tonic cholinergic inhibition.