miRNA调控Toll样受体信号通路在神经病理性疼痛中的作用*

miRNA Modulation of Toll-like Receptor Signaling in Neuropathic Pain*

摘要:

Toll样受体(Toll-like receptors, TLRs)作为先天免疫系统中的关键模式识别受体,在神经病理性疼痛的发生与发展中发挥关键作用。近年研究发现微小RNA(microRNAs, miRNAs)作为重要的基因表达调控分子,可通过多重机制调控TLR信号通路：既可作为内源性配体直接激活TLR7/8等受体,也可通过靶向TLRs及其下游信号分子进行负向调控,形成复杂的miRNA-TLR调控网络。本文系统综述了不同TLR亚型在神经损伤中的特异性作用,重点探讨了miR-21-TLR8、miR-146a-TLR4等关键调控轴在介导神经炎症和疼痛敏化的分子机制。尽管研究已证实靶向特定miRNA-TLR轴可有效缓解神经病理性疼痛,但其细胞特异性调控机制、胞外miRNA的递送路径及疾病亚型特异性网络等关键问题仍需深入解析。未来研究应整合多组学技术与精准递送策略,推动该调控网络从机制研究向临床治疗的转化,为神经病理性疼痛的精准干预提供新思路。

Abstract:

Toll-like receptors (TLRs), as key pattern recognition receptors in the innate immune system, play a central role in and development and maintenance of neuropathic pain. Emerging evidence indicates that microRNAs (miRNAs) act as important regulators of gene expression and can modulate TLR signaling through diverse mechanisms: they may serve as endogenous ligands that directly activate receptors such as TLR7/8, or exert inhibitory effects by targeting TLRs and downstream signaling molecules, collectively forming a sophisticated miRNA-TLR regulatory network. This review systematically examines the specific roles of different TLR subtypes in nervous system injury focusing on key regulatory axes—including miR-21-TLR8 and miR-146a-TLR4—in mediating neuroinflammation and pain sensitization. Although studies have demonstrated that targeting specific miRNA-TLR interactions can alleviate neuropathic pain, several critical questions remain unresolved. These include the cell-type-specificity of regulatory mechanisms, the routes of extracellular miRNA delivery, and the network specificity across disease subtypes. Future research should integrate multi-omics technologies with refined delivery strategies to advance the understanding of this regulatory network from mechanistic insight toward clinical translation, thereby opening new avenues for precision intervention in neuropathic pain.