S100A9 plays a role in neuropathic pain by regulating GPR153/Kcnk16 function in DRG neurons

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-08-29 DOI:10.1016/j.cellsig.2025.112101

Molei Liu , Dawei Han , Mingwei Sheng , Ling Liu , Lili Jia , Hongxia Li , Yiqi Weng , Yinghui Ren , Wenli Yu

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引用次数: 0

Abstract

Neuropathic pain, attributed to its intricate pathogenesis, remains challenging to treat effectively. This study delineates neuroimmune-glial cell interactions within the ganglia as a pivotal mechanism initiating nerve damage, thereby contributing to neuropathic pain. Utilizing a chronic constriction injury (CCI) mouse model, we explored the pro-inflammatory molecule S100A9, secreted by myeloid cells, in the context of neuropathic pain development. Our findings revealed an upregulation of S100A9 in the dorsal root ganglia (DRGs) of CCI mice, predominantly due to neutrophil infiltration. Notably, S100A9 knockout significantly mitigated mechanical pain hypersensitivity and inflammation induced by CCI. We further elucidated the role of S100A9 in mechanical pain hypersensitivity using inhibitors and recombinant S100A9 proteins. Transcriptome sequencing indicated that S100A9 potentially influenced neuropathic pain by modulating the expression of orphan G protein-coupled receptor 153 (GPR153) and potassium channel Kcnk16 on the DRG neuron membrane. Collectively, our research underscores the significant role of S100A9 in neuropathic pain pathogenesis and presents it as a promising therapeutic target.

Key Innovations

•
Identifies neutrophil-derived S100A9 as a key mediator of peripheral neuropathic pain.
•
Reveals a new mechanism: S100A9-GPR153-Kcnk16-CSF1, linking peripheral inflammation to central microglial activation.
•
Supports translational potential of S100A9-targeted therapies (e.g., PAQ) for pain management.

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S100A9通过调节DRG神经元中GPR153/Kcnk16的功能在神经性疼痛中发挥作用。

神经性疼痛，由于其复杂的发病机制，仍然具有挑战性的有效治疗。本研究描述神经节内的神经免疫-胶质细胞相互作用是引发神经损伤的关键机制，从而导致神经性疼痛。利用慢性收缩损伤（CCI）小鼠模型，我们探索了髓样细胞分泌的促炎分子S100A9在神经性疼痛发展中的作用。我们的研究结果揭示了CCI小鼠背根神经节（DRGs）中S100A9的上调，主要是由于中性粒细胞的浸润。值得注意的是，S100A9基因敲除显著减轻了CCI引起的机械性疼痛超敏反应和炎症。我们利用抑制剂和重组S100A9蛋白进一步阐明了S100A9在机械性疼痛超敏反应中的作用。转录组测序表明，S100A9可能通过调节DRG神经元膜上孤儿G蛋白偶联受体153 （GPR153）和钾通道Kcnk16的表达而影响神经性疼痛。总之，我们的研究强调了S100A9在神经性疼痛发病机制中的重要作用，并将其作为一个有希望的治疗靶点。关键的创新。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.