Chronic pain resulting from nerve injury, tissue inflammation, and tumor invasion or treatment, is a major health problem impacting the quality of life and producing a significant economic and social burden. However, the current analgesic drugs including non-steroidal anti-inflammatory drugs and opioids are inadequate to relieve chronic pain due to the lack of efficacy or severe side-effects. Chemokines are a family of small secreted proteins that bind to G protein-coupled receptors to trigger intracellular signaling pathways and direct cell migration, proliferation, survival, and inflammation under homeostatic and pathological conditions. Accumulating evidence supports the important role of chemokines and chemokine receptors in the peripheral and central nervous system in mediating chronic pain via enhancing neuroinflammation. In this review, we focus on recent progress in understanding the comprehensive roles of chemokines and chemokine receptors in the generation and maintenance of different types of chronic pain, including neuropathic pain, inflammatory pain, cancer pain, and visceral pain. The current review also summarizes the upstream signaling of transcriptional and epigenetic regulation on the expression of chemokines and chemokine receptors as well as the downstream signaling of chemokine receptors underlying chronic pain. As chronic itch and chronic pain share some common mechanisms, we also discuss the emerging roles of chemokines and chemokine receptors in chronic itch. Targeting specific chemokines or chemokine receptors by siRNAs, blocking antibodies, or small-molecule antagonists may offer new therapeutic potential for the management of chronic pain.

由神经损伤，组织炎症以及肿瘤浸润或治疗引起的慢性疼痛是影响生活质量并产生重大经济和社会负担的主要健康问题。然而，由于缺乏功效或严重的副作用，目前的止痛药包括非甾体类抗炎药和阿片类药物不足以缓解慢性疼痛。趋化因子是一类小分泌蛋白，与G蛋白偶联受体结合，触发细胞内信号传导途径，并在稳态和病理条件下指导细胞迁​​移，增殖，存活和炎症。越来越多的证据支持趋化因子和趋化因子受体在周围和中枢神经系统中在通过增强神经炎症来介导慢性疼痛中的重要作用。在这篇评论中 我们将重点放在了解趋化因子和趋化因子受体在不同类型的慢性疼痛（包括神经性疼痛，炎性疼痛，癌性疼痛和内脏性疼痛）的产生和维持中的综合作用方面的最新进展。本综述还总结了趋化因子和趋化因子受体表达的转录和表观遗传调控的上游信号，以及慢性疼痛背后的趋化因子受体的下游信号。由于慢性瘙痒和慢性疼痛具有一些共同的机制，因此我们还将讨论趋化因子和趋化因子受体在慢性瘙痒中的新兴作用。通过siRNA，封闭抗体或小分子拮抗剂靶向特异性趋化因子或趋化因子受体，可为慢性疼痛的治疗提供新的治疗潜力。