乳酰化在慢性疼痛发病中的研究进展*

Research Progress on Lactylation in the Pathogenesis of Chronic Pain. *

摘要:

慢性疼痛是全球重大公共卫生问题，目前，其尚未解决的关键问题包括：缺乏客观疼痛生物标志物，急性疼痛转慢性的分子临界机制不明，疼痛异质性分型标准缺失，现有疗法疗效有限且副作用突出。亟需解析疼痛慢性化核心通路与靶点，用以研发客观诊断工具与非成瘾性新型疗法。近年研究表明，乳酸不仅是能量代谢产物，还可作为表观遗传调控分子，通过乳酰化参与基因表达调控、细胞功能及疼痛进程。在慢性疼痛领域，乳酰化作为连接代谢重编程与慢性疼痛信号传导的关键环节，在多种慢性疼痛的形成过程中发挥重要作用。本文根据慢性疼痛类型、信号传导途径及慢性疼痛进程进行综述，并对乳酰化在慢性疼痛研究的发展方向作出展望，以期为临床慢性疼痛诊治提供新的思路。

Abstract:

Chronic pain represents a significant global public health challenge. Currently, the unresolved key issues include the absence of objective pain biomarkers, unclear molecular mechanisms that govern the transition from acute to chronic pain, a lack of standardized classification criteria for pain heterogeneity, and the limited efficacy and prominent side effects of existing therapies. There is an urgent need to elucidate the core pathways and targets involved in pain chronicization to develop objective diagnostic tools and non-addictive novel therapies. Recent studies have demonstrated that lactate is not merely a byproduct of energy metabolism; it also functions as an epigenetic regulatory molecule, influencing gene expression, cellular functions, and the progression of pain through lactylation. In the context of chronic pain, lactylation serves as a crucial link that connects metabolic reprogramming with chronic pain signal transduction, playing a significant role in the development of various chronic pain conditions. This article presents a review of the types of chronic pain, the associated signal transduction pathways, and the progression of chronic pain. Additionally, it offers insights into the potential development of lactylation research in chronic pain studies, aiming to provide new perspectives for the clinical diagnosis and treatment of chronic pain.