Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.

IF 5.8 2区医学 Q1 NEUROSCIENCES

Neuroscience bulletin Pub Date : 2025-10-14 DOI:10.1007/s12264-025-01519-9

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

{"title":"Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.","authors":"Junyu Lu, Yunxin Shi, Yongkang Li, Ziyi Niu, Shengxi Wu, Ceng Luo, Rou-Gang Xie","doi":"10.1007/s12264-025-01519-9","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8000,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroscience bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12264-025-01519-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

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。

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。本文讨论了目前CCL2/ ccr2靶向治疗策略及其发展现状，强调了慢性疼痛治疗的新途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neuroscience bulletin NEUROSCIENCES-

CiteScore

7.20

自引率

16.10%

发文量

163

审稿时长

6-12 weeks

期刊介绍： Neuroscience Bulletin (NB), the official journal of the Chinese Neuroscience Society, is published monthly by Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Springer. NB aims to publish research advances in the field of neuroscience and promote exchange of scientific ideas within the community. The journal publishes original papers on various topics in neuroscience and focuses on potential disease implications on the nervous system. NB welcomes research contributions on molecular, cellular, or developmental neuroscience using multidisciplinary approaches and functional strategies. We feature full-length original articles, reviews, methods, letters to the editor, insights, and research highlights. As the official journal of the Chinese Neuroscience Society, which currently has more than 12,000 members in China, NB is devoted to facilitating communications between Chinese neuroscientists and their international colleagues. The journal is recognized as the most influential publication in neuroscience research in China.