Targeting CXCR2 in Nociceptive Sensory Neurons Offers Novel Therapeutic Potentials for Postoperative Pain
6 affiliations
- 1Department of Neurobiology and Acupuncture Research The Third Clinical Medical College Key Laboratory of Acupuncture and Neurology of Zhejiang Province Zhejiang Chinese Medical University Hangzhou China
- 2Department of Pathophysiology Hebei Key Laboratory of Critical Disease Mechanism and Intervention Hebei Medical University Shijiazhuang China
- 3Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University Hangzhou China
- 4Academy of Chinese Medical Sciences Zhejiang Chinese Medical University Hangzhou China
- 5College of Pharmaceutical Sciences Hebei University Baoding China
- 6Department of Integrated Traditional Chinese and Western Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
Abstract
Postoperative pain impairs patients’ quality of life. Mechanisms underlying postoperative pain remain incompletely understood. We investigated postoperative pain in a mouse model of skin plus deep tissue incision (INC). We found Cxcl5 was among the top upregulated genes in incision site, which was produced from both incised skin and muscle. Single‐cell RNA‐sequencing reveals elevated human CXCL5 gene expression in human skin wounds. Neutralizing CXCL5 abrogated INC pain. Global knockout of CXCL5 receptor CXCR2 improved INC pain, but markedly delayed wound healing. Cxcr2 conditional knockout in nociceptive sensory neurons improved INC pain without affecting wound healing and local inflammation. CXCR2 expression and its coupling with TRPA1 were enhanced in DRG neurons innervating the incised site, resulting in neuron hyperexcitability upon CXCL5 stimulation. CXCL5 further enhances TRPV1 activity via neuronal CXCR2‐mediated signaling in DRG neurons innervating the incised site. Neuronal CXCR2‐mediated TRPV1/TRPA1 modulation synergistically contributes to heat and mechanical hypersensitivities of INC pain. Targeted Cxcr2 knockdown in incision site‐innervating DRG neurons ameliorates INC pain. Our work reveals a critical role of neuronal CXCR2 signaling in nociceptive sensory neurons that mediates INC pain via concurrently activating TRPA1 and sensitizing TRPV1. Targeting sensory neuronal CXCR2 represents a promising strategy for INC pain without affecting wound healing.
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BibTeX
@article{pan2026targeting,
title = {{Targeting CXCR2 in Nociceptive Sensory Neurons Offers Novel Therapeutic Potentials for Postoperative Pain}},
author = {Yushuang Pan and Peiyi Li and Yufeng Chen and Zishan Dong and Yuanyuan Li and Boyu Liu and Yan Tai and Chuan Wang and Jianqiao Fang and Chengyu Yin and Boyi Liu},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.77085},
url = {https://doi.org/10.1002/advs.77085},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeting CXCR2 in Nociceptive Sensory Neurons Offers Novel Therapeutic Potentials for Postoperative Pain
AU - Yushuang Pan
AU - Peiyi Li
AU - Yufeng Chen
AU - Zishan Dong
AU - Yuanyuan Li
AU - Boyu Liu
AU - Yan Tai
AU - Chuan Wang
AU - Jianqiao Fang
AU - Chengyu Yin
AU - Boyi Liu
PY - 2026
DA - 2026/08/11
JO - Advanced Science
DO - 10.1002/advs.77085
UR - https://doi.org/10.1002/advs.77085
AB - Postoperative pain impairs patients’ quality of life. Mechanisms underlying postoperative pain remain incompletely understood. We investigated postoperative pain in a mouse model of skin plus deep tissue incision (INC). We found Cxcl5 was among the top upregulated genes in incision site, which was produced from both incised skin and muscle. Single‐cell RNA‐sequencing reveals elevated human CXCL5 gene expression in human skin wounds. Neutralizing CXCL5 abrogated INC pain. Global knockout of CXCL5 receptor CXCR2 improved INC pain, but markedly delayed wound healing. Cxcr2 conditional knockout in nociceptive sensory neurons improved INC pain without affecting wound healing and local inflammation. CXCR2 expression and its coupling with TRPA1 were enhanced in DRG neurons innervating the incised site, resulting in neuron hyperexcitability upon CXCL5 stimulation. CXCL5 further enhances TRPV1 activity via neuronal CXCR2‐mediated signaling in DRG neurons innervating the incised site. Neuronal CXCR2‐mediated TRPV1/TRPA1 modulation synergistically contributes to heat and mechanical hypersensitivities of INC pain. Targeted Cxcr2 knockdown in incision site‐innervating DRG neurons ameliorates INC pain. Our work reveals a critical role of neuronal CXCR2 signaling in nociceptive sensory neurons that mediates INC pain via concurrently activating TRPA1 and sensitizing TRPV1. Targeting sensory neuronal CXCR2 represents a promising strategy for INC pain without affecting wound healing.
SN - 2198-3844
ER -