Neutrophil extracellular traps as a unique target in the treatment of inflammatory pain

作者全名：Qin, Wanxiang; Li, Yuping; Cui, Jian; Yu, Bao; Yu, Lehua; Yang, Congwen

作者地址：[Qin, Wanxiang; Yu, Lehua; Yang, Congwen] Chongqing Med Univ, Affiliated Hosp 2, Dept Rehabil Med, Chongqing 400010, Peoples R China; [Qin, Wanxiang; Li, Yuping; Cui, Jian] Army Med Univ, Affiliated Hosp 1, Dept Pain Med, Chongqing 400038, Peoples R China; [Yu, Bao] Chongqing Coll Tradit Chinese Med, Coll Tradit Chinese Med, Chongqing 402760, Peoples R China; [Yang, Congwen] Chongqing Med Univ, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China

通信作者：Yang, CW (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Rehabil Med, Chongqing 400010, Peoples R China.

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001228437300001

JCR分区：Q3

影响因子：2.5

年份：2024

卷号：710

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Inflammatory pain; Neutrophils; Neutrophil extracellular traps; NF-kappa B; Inflammation

摘要：Pain is a widespread motivation for seeking healthcare and stands as a substantial global public health concern. Despite comprehensive investigations into the mechanisms of pain sensitization induced by inflammation, efficacious treatments options remain scarce . Neutrophil extracellular traps (NETs) have been associated with the progression and tissue damage of diverse inflammatory diseases. This study aims to explore the impact of NETs on the progression of inflammatory pain and explore potential therapeutic approaches. Initially, we observed neutrophil infiltration and the formation of NETs in the left hind paw of mice with inflammatory pain induced by complete Freund 's adjuvant (CFA). Furthermore, we employed the peptidyl arginine deiminase 4 (PAD4) inhibitor Cl-amidine (diluted at 50 mg/kg in saline, administered via tail vein injection once daily for three days) to impede NETs formation and administered DNase1 (diluted at 10 mg/kg in saline, once daily for three days) to break down NETs. We investigated the pathological importance of peripheral NETs formation in inflammatory pain and its influence on the activation of spinal dorsal horn microglia. The findings indicate that neutrophils infiltrating locally generate NETs, leading to an increased release of inflammatory mediators that worsen peripheral inflammatory reactions. Consequently, this results in the transmission of more harmful peripheral stimuli to the spinal cord, triggering microglial activation and NF- kappa B phosphorylation, thereby escalating neuroinflammation and fostering pain sensitization. Suppression of peripheral NETs can mitigate peripheral inflammation in mice with inflammatory pain, reverse mechanical and thermal hypersensitivity by suppressing microglial activation in the spinal cord, ultimately diminishing inflammatory pain. In conclusion, these discoveries propose that obstructing or intervening with NETs introduces a novel therapeutic avenue for addressing inflammatory pain.

基金机构：National Natural Science Foundation of China [81870883]; Science and Technology Project Affiliated to the Education Department of Chongqing Municipality [KJZD-K202215104]; Chongqing Clinical Key Specialty Construction Project Funding [CQZDZK001]; Joint project of Chongqing Health Commission and Science and Technology Bureau [2021MSXM006]

基金资助正文：This study was funded by National Natural Science Foundation of China (No. 81870883) , The Science and Technology Project Affiliated to the Education Department of Chongqing Municipality (KJZD-K202215104) , 2019 Chongqing Clinical Key Specialty Construction Project Funding (CQZDZK001) and Joint project of Chongqing Health Commission and Science and Technology Bureau (2021MSXM006) .