Research progress on the neural mechanisms of alcohol use disorder-induced hyperalgesia
MA Ling-Jie1, CHEN Xiao-Hong2, GAO Yong-Jing1,*
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
Received: Accepted:
Corresponding author: 高永静 E-mail:
DOI: 10.13294/j.aps.2026.0016
Citing This Article:
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).