One of the fundamental mechanisms whereby the innate immune system coordinates inflammatory signal transduction is through Toll-like receptors (TLRs), which function to protect and defend the host organism by initiating inflammatory signaling cascades in response to tissue damage or injury. TLRs are positioned at the neuroimmune interface, and accumulating evidence suggests that the inflammatory consequences of TLR activation on glia (including microglia and astrocytes), sensory neurons, and other cell types can influence nociceptive processing and lead to states of exaggerated and unresolved pain. In this review, we summarize our current understanding of how different TLRs and their accessory or adaptor molecules can contribute to the development and maintenance of persistent pain. The challenges and opportunities of targeting TLRs for new treatment strategies against chronic pain are discussed, including the therapeutic context of TLR-mediated signaling in opioid analgesia and chemotherapy-induced pain. Considering the prevalence of persistent pain and the insufficient efficacy and safety of current treatment options, a deeper understanding of Toll-like receptors holds the promise of novel therapies for managing pathological pain.

先天性免疫系统协调炎症信号转导的基本机制之一是通过Toll样受体（TLR），其通过响应组织损伤或损伤而启动炎症信号级联，从而起到保护和防御宿主生物的作用。TLR位于神经免疫界面，越来越多的证据表明TLR激活对神经胶质（包括小神经胶质细胞和星形胶质细胞），感觉神经元和其他细胞类型的炎性后果会影响伤害感受过程，并导致疼痛加剧和无法解决。在这篇综述中，我们总结了我们目前对不同的TLR及其辅助分子或衔接子分子如何促进持续性疼痛的形成和维持的理解。讨论了针对新的针对慢性疼痛的治疗策略针对TLR的挑战和机遇，包括阿片类镇痛和化学疗法诱发的疼痛中TLR介导的信号传导的治疗背景。考虑到持续性疼痛的普遍性以及当前治疗方案的功效和安全性不足，对Toll样受体的更深入了解为治疗病理性疼痛的新型疗法带来了希望。