Department of Biology, University of Utah, Salt Lake City, UT, USA.
Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), IBITECS, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
Br J Pharmacol. 2018 Jun;175(11):1915-1927. doi: 10.1111/bph.13931. Epub 2017 Jul 30.
Neuropathic pain is a complex and debilitating syndrome for which there are few effective pharmacological treatments. Opioid-based medications are initially effective for acute pain, but tolerance to their analgesic effects quickly develops, and long-term use often leads to physical dependence and addiction. Furthermore, neuropathic pain is generally resistant to non-steroidal anti-inflammatory drugs. Other classes of medications including antidepressants, antiepileptics and voltage-gated calcium channel inhibitors are only partially effective in most patients, may be associated with significant side effects and have few disease-modifying effects on the underlying pathology. Medications that act through new mechanisms of action, and particularly ones that have disease-modifying properties, would be highly desirable. In the last decade, a potential new target for the treatment of neuropathic pain has emerged: the α9-containing nicotinic acetylcholine receptor (nAChR). Recent studies indicate that antagonists of α9-containing nAChRs are analgesic in animal models of neuropathic pain. These nerve injury models include chronic constriction injury, partial sciatic nerve ligation, streptozotocin-induced diabetic neuropathy and chemotherapeutic-induced neuropathy. This review details the history and state of the field regarding the role that α9-containing nAChRs may play in neuropathic pain. An alternative hypothesis that α-conotoxins exert their therapeutic effect through blocking N-type calcium channels via activation of GABA receptors is also reviewed. Understanding how antagonists of α9-containing nAChRs exert their therapeutic effects may ultimately result in the development of medications that not only treat but also prevent the development of neuropathic pain states.
This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.
神经性疼痛是一种复杂且使人虚弱的综合征，目前针对这种疼痛，有效的药物疗法寥寥无几。阿片类药物起初对急性疼痛有效，但很快就会产生对其镇痛效果的耐受性，长期使用往往会导致身体依赖和成瘾。此外，神经性疼痛通常对非甾体类抗炎药有抵抗力。其他类药物，包括抗抑郁药、抗癫痫药和电压门控钙通道抑制剂，在大多数患者中仅部分有效，可能会引起严重的副作用，对潜在的病理改变几乎没有治疗作用。作用于新作用机制的药物，特别是具有治疗作用的药物，是非常理想的。在过去的十年中，治疗神经性疼痛的一个新的潜在靶点已经出现：含α9 的烟碱型乙酰胆碱受体 (nAChR)。最近的研究表明，含α9 的 nAChR 拮抗剂在神经性疼痛的动物模型中具有镇痛作用。这些神经损伤模型包括慢性缩窄性损伤、部分坐骨神经结扎、链脲佐菌素诱导的糖尿病神经病变和化疗诱导的神经病变。本综述详细介绍了含α9 的 nAChR 在神经性疼痛中的作用的历史和现状。另一种假说认为，α- 芋螺毒素通过激活 GABA 受体来阻断 N 型钙通道，从而发挥其治疗作用，这一假说也得到了综述。了解含α9 的 nAChR 拮抗剂如何发挥其治疗作用，最终可能会开发出不仅能治疗而且能预防神经性疼痛状态发展的药物。
本文是关于烟碱型乙酰胆碱受体的专题部分的一部分。要查看该部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.
