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酒精使用障碍引起痛觉过敏的神经机制研究进展

马灵杰¹, 陈小红², 高永静^1,*

¹南通大学特种医学研究院，南通 226019；²南通大学附属肿瘤医院麻醉科，南通 226006

摘要

酒精使用障碍(alcohol use disorder, AUD)是一种复杂的慢性复发性脑部疾病，对个体健康和公共卫生构成重大影响。痛觉过敏是导致AUD治疗失败的关键因素。现有药物不能有效缓解AUD患者的疼痛，因而亟需研发新的干预措施。本文系统综述了AUD导致痛觉过敏的多系统神经生物学机制，从分子到环路，再从中枢到外周，揭示了神经递质失衡[如谷氨酸能兴奋增强/γ-氨基丁酸(γ-aminobutyric acid, GABA)能抑制]、神经胶质细胞介导的神经炎症等经典通路，并深入分析了表观遗传调控(DNA甲基化、组蛋白修饰和microRNA对关键基因的表达调控)和肠-脑轴(肠道菌群通过代谢物影响中枢神经系统)等新型机制，同时强调了性激素介导的性别差异性。基于这些见解，本文提出靶向神经环路、表观遗传修饰酶、肠道菌群等新型干预策略，为临床治疗AUD引起的痛觉过敏提供新视角，这对降低复饮率、改善患者预后具有重要意义。

关键词： 酒精使用障碍; 痛觉过敏; 神经递质; 胶质细胞; 神经炎症; 表观遗传; 肠-脑轴

Research progress on the neural mechanisms of alcohol use disorder-induced hyperalgesia

MA Ling-Jie¹, CHEN Xiao-Hong², GAO Yong-Jing^1,*

¹Institute of Special Environmental Medicine, Nantong University, Nantong 226019, China；²Department of Anesthesiology of the Affiliated Tumor Hospital, Nantong University, Nantong 226006, China

Abstract

Alcohol use disorder (AUD) is a complex chronic relapsing brain disease that poses significant threats to individual health and public healthcare systems. Hyperalgesia, an increased sensitivity to pain, has been recognized as a critical factor leading to treatment failure in AUD management. Existing pharmacotherapies inadequately alleviate pain symptoms in AUD patients, highlighting an urgent need for novel therapeutic strategies. This review systematically summarizes the multi-system neurobiological mechanisms underlying AUD-induced hyperalgesia, spanning from molecular to circuit levels, and from the central to the peripheral nervous systems. It elucidates classic pathways including neurotransmitter imbalances (e. g., enhanced glutamatergic excitation and weakened GABAergic inhibition) and glial cell-mediated neuroinflammation. This article conducts an in-depth analysis of emerging mechanisms including epigenetic regulation (DNA methylation, histone modifications, and microRNA-mediated expression control of key genes) and the gut-brain axis (where gut microbiota influence the central nervous system via metabolites), while emphasizing sex hormone mediated gender differences. Based on these insights, we propose novel intervention strategies targeting neural circuits, epigenetic modifying enzymes, and gut microbiota, offering new perspectives for clinical treatment of AUD-induced hyperalgesia, which holds significant promise for reducing relapse rates and improving patient prognosis.

Key words: alcohol use disorder; hyperalgesia; neurotransmitters; glial cells; neuroinflammation; epigenetics; gut-brain axis

收稿日期：　　录用日期：

通讯作者：高永静　　E-mail:

DOI: 10.13294/j.aps.2026.0016

引用本文：

马灵杰, 陈小红, 高永静. 酒精使用障碍引起痛觉过敏的神经机制研究进展[J]. 生理学报 2026; 78 (1): 109-122.

MA Ling-Jie, CHEN Xiao-Hong, GAO Yong-Jing. Research progress on the neural mechanisms of alcohol use disorder-induced hyperalgesia. Acta Physiol Sin 2026; 78 (1): 109-122 (in Chinese with English abstract).