Electroacupuncture Alleviates Neuropathic Pain by Inhibiting Spinal CCL2-Driven Microglial Activation.

Abstract

Electroacupuncture (EA) has shown analgesic potential for neuropathic pain, yet its underlying molecular mechanisms remain incompletely understood. This study aimed to investigate whether EA relieves neuropathic pain by modulating CCL2/CCR2 signaling and microglial activation in the spinal cord. Neuropathic pain was induced in rats by L5 spinal nerve ligation. EA was administered at acupoints ST36 and GB34 (1 mA, 2 Hz, 30 min) daily from postoperative days 3 to 7. Rats were assigned to anesthetized control (ANE), non-acupoint stimulation (NAP), and acupoint stimulation (ACU) groups. Pain behavior was evaluated using paw withdrawal threshold and latency. Western blot and immunofluorescence were used to assess CCL2, CCR2, Iba1, IL-1β, and TNF-α expression in the L4-L6 spinal cord. EA significantly attenuated mechanical allodynia and thermal hyperalgesia in the ACU group, accompanied by reductions in CCL2, CCR2, microglial marker Iba1, and pro-inflammatory cytokines. Most importantly, intrathecal administration of recombinant CCL2 completely abolished EA's analgesic effects, establishing the causal necessity of CCL2/CCR2 signaling in EA-mediated analgesia. These findings suggest that EA exerts its analgesic effects through downregulation of the CCL2/CCR2 pathway and inhibition of microglial activation. The reversal of EA's effects by exogenous CCL2 supports the critical role of spinal chemokine signaling in EA-mediated analgesia.