Targeting CXCR2 in Nociceptive Sensory Neurons Offers Novel Therapeutic Potentials for Postoperative Pain

Yushuang Pan1, Peiyi Li1, Yufeng Chen1

  • 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.

Insights

Chemokine CXCL5 (chemoattractant cytokine ligand 5) drives postoperative pain by activating CXCR2 on sensory neurons. Targeting this pathway offers pain relief without hindering wound healing.

Area of Science:

  • Neuroscience
  • Immunology
  • Pain Research

Background:

  • Postoperative pain significantly impacts patient quality of life.
  • The underlying mechanisms of postoperative pain are not fully understood.
  • CXCL5 is identified as a key molecule in pain signaling.

Purpose of the Study:

  • To investigate the role of CXCL5 and its receptor CXCR2 in postoperative incisional pain (INC).
  • To explore the therapeutic potential of targeting the CXCL5-CXCR2 axis in sensory neurons for pain management.

Main Methods:

  • Utilized a mouse model of skin and deep tissue incision (INC).
  • Employed gene expression analysis, single-cell RNA-sequencing, and neutralizing antibodies.
  • Generated global and conditional knockout mice for CXCR2.
  • Investigated neuronal excitability and ion channel function (TRPA1, TRPV1) in dorsal root ganglion (DRG) neurons.

Main Results:

  • CXCL5 expression was upregulated at the incision site and in human skin wounds.
  • Neutralizing CXCL5 or knocking out CXCR2 in sensory neurons reduced INC pain.
  • Global CXCR2 knockout improved pain but delayed wound healing.
  • CXCR2 signaling in DRG neurons enhanced TRPA1 and TRPV1 activity, contributing to hypersensitivity.
  • Targeted knockdown of CXCR2 in sensory neurons alleviated pain without affecting wound healing.

Conclusions:

  • Neuronal CXCR2 signaling is critical for mediating INC pain by modulating TRPA1 and TRPV1 channels.
  • Targeting sensory neuronal CXCR2 is a promising strategy for managing postoperative pain.
  • This approach offers pain relief without compromising wound healing or local inflammation.