第四军医大学解柔刚小组宣布他们的最新研究揭示了趋化因子CCL2介导神经胶质相互作用并驱动慢性疼痛发病机制。该研究于2025年10月14日发表于国际一流学术期刊《神经科学通报》杂志上。

慢性疼痛常常与神经精神疾病合并症，严重损害患者的生活质量和功能能力。越来越多的证据表明趋化因子CCL2及其受体CCR2在慢性疼痛发病机制中起着关键作用。本文从三个层次探讨了CCL2/CCR2轴在慢性疼痛加工中的调节机制：(1)外周致敏：CCL2/CCR2调节TRPV1、Nav1.8和HCN2通道，增加外周伤害感受器的神经元兴奋性和CGRP信号和钙依赖性胞外分泌，以传递疼痛。(2)脊髓中枢致敏：CCL2/CCR2参与NMDAR依赖性可塑性、胶质细胞激活、GABA能去抑制和阿片受体脱敏。(3)棘上中枢网络：CCL2/CCR2信号轴在ACC、CeA、NAc、海马等脑区介导疼痛与焦虑、认知障碍的共病机制，并通过下行促进系统增加疼痛致敏。本文阐述了目前CCL2/CCR2靶向治疗策略及其发展状况，强调了慢性疼痛治疗的新途径。

附：英文原文

Title: Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis

Author: Lu, Junyu, Shi, Yunxin, Li, Yongkang, Niu, Ziyi, Wu, Shengxi, Luo, Ceng, Xie, Rou-Gang

Issue&Volume: 2025-10-14

Abstract: Chronic pain, frequently comorbid with neuropsychiatric disorders, significantly impairs patients’ quality of life and functional capacity. Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis. This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels: (1) Peripheral Sensitization: CCL2/CCR2 modulates TRPV1, Nav1.8, and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain. (2) Spinal Cord Central Sensitization: CCL2/CCR2 contributes to NMDAR-dependent plasticity, glial activation, GABAergic disinhibition, and opioid receptor desensitization. (3) Supraspinal Central Networks: CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions, including the ACC, CeA, NAc, and hippocampus, and it also increases pain sensitization through the descending facilitation system. Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed, highlighting novel avenues for chronic pain management.

DOI: 10.1007/s12264-025-01519-9

Source: https://link.springer.com/article/10.1007/s12264-025-01519-9