《生命科学》 2026, 38(10): 1742-1753
乙酰胆碱受体作为镇痛靶点的研究进展
摘 要：
乙酰胆碱受体（acetylcholine receptor， AChR）广泛分布于中枢及外周神经系统，分为烟碱型（nicotinic acetylcholine receptor， nAChR）和毒蕈碱型 （muscarinic acetylcholine receptor， mAChR）两大类。这两类受体直接参与痛觉感知与信号传导过程，在急性痛、慢性炎症痛及神经病理痛的发生发展中发挥重要调控作用。本文综述了α4β2、α7、α9α10 nAChR及M1、M2、M3、M4 mAChR亚型的特异性镇痛功能及相关调控机制，同时梳理了针对不同受体亚型的激动剂与变构调节剂的研究进展。各受体亚型所展现出的独特镇痛潜力与调控特征不仅为深入解析疼痛的分子调控网络奠定基础，更为后续镇痛策略的优化升级与低成瘾性镇痛药物的靶向开发提供理论参考与实验支撑。
通讯作者：盛海燕 , Email:shenghy@xxmu.edu.cn
Abstract:
As a key molecule mediating acetylcholine signal transduction in the nervous system, the acetylcholine receptor (AChR) is widely distributed in the central and peripheral nervous systems. Based on their structural and functional characteristics, AChRs are classified into two main types: nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs). Both types of receptors are directly involved in nociceptive perception and signal conduction, and play crucial regulatory roles in various animal models of pain, including acute pain, chronic inflammatory pain, and neuropathic pain. This review summarizes the specific analgesic functions and related regulatory mechanisms of α4β2, α7, and α9α10 nAChR subtypes as well as M1, M2, M3, and M4 mAChR subtypes. The contents include the advantages of novel compounds targeting α4β2 receptors in avoiding opioid addiction and respiratory depression risks and exerting synergistic analgesic effects; the characteristics of α7 receptors in mediating immune microenvironment regulation and anti-inflammatory effects, along with their dual regulatory capacity in pain sensation and pain emotion; targeting α9α10 receptors to alleviate chemotherapy-induced pain; targeting M1 receptors for the treatment of diabetic neuropathy; and the potential of M3 receptors as molecules in neuro-immune crosstalk regulation. Meanwhile, this review systematically outlines the research progress of agonists and allosteric modulators targeting different receptor subtypes, covering the combined administration strategy of bufalin (a natural compound activating α4β2 receptors) and traditional analgesics; the combined regimen of xanomeline (an M1 receptor agonist) and peripheral anticholinergics; and the strategy of constructing analgesic drugs targeting M2 receptor activation via molecular hybridization of orthosteric agonists and allosteric modulators. The distinct analgesic potential and regulatory mechanisms exhibited by various receptor subtypes not only lay a foundation for in-depth analysis of the molecular regulatory network of pain, but also provide guidance for breaking through the bottlenecks of traditional analgesics associated with high addiction liability and prominent side effects, as well as theoretical references and experimental support for optimizing and upgrading subsequent analgesic strategies and developing targeted low-addiction analgesic drugs.
Communication Author：SHENG Hai-Yan , Email:shenghy@xxmu.edu.cn
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