Chen Zhangwei, Xia Yunfan, Liu Boyi, Fang Jianqiao, Hu Qimiao
The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
J Pain Res. 2025 May 21;18:2583-2603. doi: 10.2147/JPR.S509541. eCollection 2025.
Chronic pain greatly affects patients' quality of life and poses significant challenges for the healthcare system. Conventional medication is generally inadequate for managing chronic pain and frequently leads to numerous adverse effects. The chemokine C-X-C motif ligand 12 (CXCL12) and its receptor, the chemokine C-X-C motif receptor 4 (CXCR4), are emerging as significant neuromodulators within the nervous system. A growing body of evidence has underscored the critical roles of this chemokine axis in the development and persistence of pathological pain. In this review, we aim to synthesize recent findings that highlight the role and mechanisms of the CXCL12/CXCR4 axis in the etiology of chronic pain conditions. We focus on chronic pain stemming from sciatic nerve injury, diabetic neuropathy, spinal cord injury, bone cancer, opioid tolerance, and opioid-induced hyperalgesia. These conditions represent a diverse range of pathologies that underscore the broad impact of the CXCL12/CXCR4 axis in pain management. Furthermore, we discuss the potential for targeting the CXCL12/CXCR4 axis as a comprehensive therapeutic strategy for chronic pain. In this review, we aim to summarize emerging evidence on the critical role of the CXCL12/CXCR4 signaling in mediating chronic pain pathogenesis and its potential contributions to neurological disorders.
慢性疼痛极大地影响患者的生活质量，并给医疗保健系统带来重大挑战。传统药物通常不足以治疗慢性疼痛，且常常会导致众多不良反应。趋化因子C-X-C基序配体12（CXCL12）及其受体趋化因子C-X-C基序受体4（CXCR4），正成为神经系统中重要的神经调节因子。越来越多的证据强调了该趋化因子轴在病理性疼痛的发生和持续过程中的关键作用。在本综述中，我们旨在综合近期的研究发现，突出CXCL12/CXCR4轴在慢性疼痛病症病因学中的作用及机制。我们重点关注由坐骨神经损伤、糖尿病性神经病变、脊髓损伤、骨癌、阿片类药物耐受性和阿片类药物诱导的痛觉过敏引起的慢性疼痛。这些病症代表了多种病理情况，突显了CXCL12/CXCR4轴在疼痛管理中的广泛影响。此外，我们讨论了将CXCL12/CXCR4轴作为慢性疼痛综合治疗策略的潜力。在本综述中，我们旨在总结关于CXCL12/CXCR4信号传导在介导慢性疼痛发病机制中的关键作用及其对神经疾病潜在影响的新证据。
