Electroacupuncture alleviates inflammatory pain by modulating the CXCL1/CXCR2 signaling axis in the spinal cord dorsal horn of rats.

AIMS: To elucidate the function of the C-X-C motif chemokine ligand 1 (CXCL1)-C-X-C Motif Chemokine Receptor 2 (CXCR2) signaling axis within the Spinal Cord Dorsal Horn (SCDH) in mediating the antinociceptive effects of electroacupuncture (EA) on pain. MAIN METHODS: An inflammatory pain model was created by injecting 0.1 ml of Complete Freund's Adjuvant into the right foot of Wistar rats. EA was then applied daily for 7 days at the Zusanli and Kunlun points, using a 2/100 Hz wave pattern and gradually increasing the current from 0.5 mA to 1.5 mA. Pain thresholds were measured, and effective pain relief was confirmed. The spinal dorsal horn was analyzed for CXCL1 content via ELISA, CXCR2 expression via Western blotting, and gene expression via PCR. Intrathecal catheterization was used to administer recombinant CXCL1 or the CXCR2 antagonist SB225002 to study their effects on EA's pain relief. KEY FINDINGS: (1) Electroacupuncture demonstrates substantial analgesic effects in rats experiencing inflammatory pain, notably increasing the thermal and mechanical pain thresholds in the plantar region of the affected limb. (2) Findings from enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analyses reveal that, EA significantly downregulates the protein levels of CXCL1 and CXCR2 in the dorsal horn of the spinal cord in rats with inflammatory pain, and decreases the expression levels of the inflammatory cytokine IL-1β in serum.(3) PCR results indicated that EA significantly reduced CXCL1 and CXCR2 mRNA levels in the spinal cord's dorsal horn, highlighting its gene regulatory effect. (4) Subsequent pretreatment with recombinant CXCL1 protein counteracted the analgesic effects of EA. In contrast, intrathecal administration of the CXCR2 antagonist SB225002 replicated these effects and led to a significant reduction in serum IL-1β levels. (5) Finally, the administration of recombinant CXCL1 and CXCR2 antagonists substantiated that CXCL1 and CXCR2 serve as pivotal regulatory targets for the analgesic effects of EA. The upregulation of CXCL1 diminishes these effects, whereas the antagonism of CXCR2 amplifies them. SIGNIFICANCE: Electroacupuncture alleviates chronic inflammatory pain in rats by targeting the CXCL1-CXCR2 signaling axis in the SCDH, reducing CXCL1, CXCR2, and serum IL-1β levels, making it a potential therapeutic target.