Immune cells are involved in the pathogenesis of pain by directly activating or sensitizing nociceptor sensory neurons. However, because the immune system also has the capacity to self-regulate through anti-inflammatory mechanisms that drive the resolution of inflammation, it might promote pain resolution and prevention. Here, we describe how immune cell-derived cytokines can act directly on sensory neurons to inhibit pain hypersensitivity and how immune-derived endogenous opioids promote analgesia. We also discuss how immune cells support healthy tissue innervation by clearing debris after nerve injury, protecting against axon retraction from target tissues and enhancing regeneration, preventing the development of chronic neuropathic pain. Finally, we review the accumulating evidence that manipulating immune activity positively alters somatosensation, albeit with currently unclear molecular and cellular mechanisms. Exploration of immune-mediated analgesia and pain prevention could, therefore, be important for the development of novel immune therapies for the treatment of clinical pain states.

免疫细胞通过直接激活或敏感伤害感受器感觉神经元参与疼痛的发病机制。然而，由于免疫系统还具有通过驱动炎症消退的抗炎机制进行自我调节的能力，因此它可能会促进疼痛的消退和预防。在这里，我们描述了免疫细胞衍生的细胞因子如何直接作用于感觉神经元以抑制疼痛超敏反应，以及免疫衍生的内源性阿片类药物如何促进镇痛。我们还讨论了免疫细胞如何通过清除神经损伤后的碎片、防止轴突从靶组织回缩和增强再生、防止慢性神经性疼痛的发展来支持健康的组织神经支配。最后，我们回顾了越来越多的证据表明，操纵免疫活动会积极改变体感，尽管目前分子和细胞机制尚不清楚。因此，探索免疫介导的镇痛和疼痛预防对于开发治疗临床疼痛状态的新型免疫疗法可能很重要。