Molecular mechanism for analgesia involving specific antagonism of α9α10 nicotinic acetylcholine receptors
Molecular mechanism for analgesia involving specific antagonism of α9α10 nicotinic acetylcholine receptors
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DOI：
10.1073/pnas.0608715103
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发表时间：
2006-11
期刊：
影响因子：
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通讯作者：
M. Vincler;Shannon Wittenauer;Renee A. Parker;M. Ellison;B. Olivera;J. McIntosh
中科院分区：
文献类型：
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作者：
M. Vincler;Shannon Wittenauer;Renee A. Parker;M. Ellison;B. Olivera;J. McIntosh
α9α10烟碱型乙酰胆碱受体（nAChR）已在多种组织中发现，包括淋巴细胞和背根神经节;除听觉系统外，α9α10 nAChR的功能尚不清楚。在这里，我们表明，选择性阻断（而不是刺激）α9α10 nAChRs是镇痛神经损伤疼痛的动物模型。此外，阻断这种nAChR亚型可减少损伤部位胆碱乙酰转移酶阳性细胞、巨噬细胞和淋巴细胞的数量。据估计，慢性神经性疼痛影响高达8%的世界人口;目前可用的许多镇痛化合物在很大程度上是无效的，并通过少数药理学机制起作用。我们的研究结果不仅提示了治疗神经病理性疼痛的分子机制，而且还证实了α9α10 nAChRs参与外周神经损伤的病理生理学。
α9α10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except in the case of the auditory system, the function of α9α10 nAChRs is not known. Here we show that selective block (rather than stimulation) of α9α10 nAChRs is analgesic in an animal model of nerve injury pain. In addition, blockade of this nAChR subtype reduces the number of choline acetyltransferase-positive cells, macrophages, and lymphocytes at the site of injury. Chronic neuropathic pain is estimated to affect up to 8% of the world's population; the numerous analgesic compounds currently available are largely ineffective and act through a small number of pharmacological mechanisms. Our findings not only suggest a molecular mechanism for the treatment of neuropathic pain but also demonstrate the involvement of α9α10 nAChRs in the pathophysiology of peripheral nerve injury.