Electroacupuncture ameliorated neuropathic pain induced by chronic constriction injury via inactivation of PI3K/AKT pathway

Objective: To explore the analgesic effect of electroacupuncture on neuropathic pain and the role of PI3K/AKT pathway in microglial activation in spinal cord. Methods: Chronic constriction injury model was established using Sprague-Dawley rats to mimic neuropathic pain. The pain intensity was then detected by paw withdrawal threshold and thermal withdrawal latency. Real-time quantitative PCR (qRT-PCR), Western blot were used to evaluate the activation of PI3K/AKT pathway as well as microglia in L4-5 of all rats. Proinflammatory cytokines TNF-alpha and IL-6 were analyzed by Enzyme-linked immunosorbent assay (ELISA). Results: It was demonstrated that chronic constriction injury-induced hyperalgesia was significantly improved by LY294002 intrathecal administration and electroacupuncture stimulation at "Zusanli" (sic) (ST36) and "Yanglingquan" (sic) (GB34). Also, treatment with electroacupuncture significantly reduced the activation of microglia and downregulated the levels of TNF-alpha and IL-6, which was similar to the outcomes of LY294002 intrathecal administration. Furthermore, the expression and phosphorylation of PI3K/AKT signaling was markedly suppressed by electroacupuncture treatment. Conclusions: These findings indicated that electroacupuncture exhibited the analgesic effect on CCI rats by inhibiting the activation of microglia and production of proinflammatory cytokines in spinal cord through blocking the microglial PI3K/AKT signaling activation.