Electroacupuncture at 5/100 Hz alleviates neuropathic pain in rats by inhibiting the CCL3/CCR5 axis in the spinal cord

Objective: Typically, neuropathic pain (NP) is difficult to manage as it is refractory to conventional medications. Electroacupuncture (EA) at 5/100 Hz has emerged as an effective and promising treatment for NP; however, its mechanism of action is still uncertain. Accordingly, this study investigated the alleviatory mechanism of EA in chronic compression injury (CCI)-induced chronic pain via the C–C chemokine ligand 3 / C–C chemokine receptor type 5 (CCL3/CCR5) axis. Methods: The CCI model was established in rats to induce NP. Mechanical and thermal hyperalgesia were assessed with von Frey and Hargreaves tests, respectively. From day 8 after CCI, EA (5/100 Hz) was performed for 1 week (30 min/day). CCL3 and CCR5 expression was detected with Western blotting and immunofluorescence. Glial cell activation was determined through co-labeling of neurons and glial cells with antibodies against CCL3 and CCR5. The release of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was tested with enzyme-linked immunosorbent assay (ELISA). Results: EA markedly ameliorated CCI-induced chronic NP in rats and reduced CCL3 and CCR5 expression in the rat spinal cord. CCL3 and CCR5 were co-expressed by neurons and microglia in the central nervous system. In addition, EA also repressed the activation of glial cells and levels of IL-1β, IL-6 and TNF-α. Conclusion: EA may mitigate chronic NP in rats by blocking the CCL3/CCR5 axis in the spinal cord. In addition, EA appeared to exert anti-inflammatory and analgesic effects by suppressing glial cell activation. These findings add to our understanding of the mechanism of EA-induced analgesia.