Abstract

Neuropathic pain in cervical spondylotic radiculopathy (CSR) remains a therapeutic challenge, with mounting evidence implicating microglia-driven neuroinflammation as a key contributor. Here, we demonstrate that electroacupuncture (EA) at Jiaji (EX-B2) acupoints relieves CSR-induced neuropathic pain by targeting microglial signal transducer and activator of Transcription 3 (STAT3) signaling. In a CSR rat model, EA significantly improved sensorimotor outcomes. EA suppressed STAT3 phosphorylation in dorsal horn microglia, accompanied by reduced expression of proinflammatory cytokines (TNF- α and IL-6) and reactive oxygen species (ROS). In vitro, serum from EA-treated rats replicated these anti-inflammatory effects in lipopolysaccharide (LPS)–activated BV-2 microglial cells. Mechanistically, EA inhibited microglial STAT3 activation and upregulated the mitochondrial complex I subunit NDUFA13, restoring mitochondrial membrane potential and limiting oxidative stress. Furthermore, EA reversed CSR-induced imbalances in spinal nociceptive (CGRP) and axonal structural (NF200) markers, promoting a homeostatic microenvironment. Together, these findings identify microglial STAT3 as a critical target of EA and reveal a “STAT3–mitochondrial axis” underlying its analgesic effect. Our study provides a mechanistic rationale for applying Jiaji acupoints EA in CSR-induced neuropathic pain and potentially other neuroinflammatory disorders.