• Jin Xu, Xue-Mei Chen, Bei-Jie Zheng, and Xiang-Rui Wang.
• From the Department of Anesthesiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
• Anesth. Analg. 2016 Mar 1; 122 (3): 882-892.

BackgroundElectroacupuncture (EA) has therapeutic effects on neuropathic pain induced by nerve injury; however, the underlying mechanisms remain unclear. In this study, we examined whether EA treatment relieves pain hypersensitivity via the down-regulation of spinal P2X7 receptor-positive (P2X7R⁺) microglia-mediated overexpression of interleukin (IL)-1β and/or IL-18.MethodsMale Sprague-Dawley rats underwent chronic constriction injury (CCI) or 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) intrathecal injection. Von Frey and Hargreaves tests were performed to evaluate the effect of EA on pain hypersensitivity. The spinal P2X7R, IL-1β, and IL-18 expression levels were determined by real-time polymerase chain reaction, Western blot analysis, immunofluorescence staining, and enzyme-linked immunosorbent assay. The selective P2X7R antagonist A-438079 was used to examine the P2X7R⁺ microglia-dependent release of IL-1β and IL-18. Primary cultures were subsequently used to assess the P2X7R⁺ microglia-induced IL-1β and IL-18 release.ResultsEA treatment significantly improved the pain thresholds and inhibited spinal P2X7R⁺ microglia activation induced by CCI or BzATP administration, which was accompanied by the suppression of spinal IL-1β and IL-18 overexpression. Moreover, A-438079 also improved pain thresholds and suppressed overexpression of IL-1β in the CCI- and BzATP-injected rats. The analysis of cultured microglia further demonstrated that A-438079 markedly decreased BzATP-induced IL-1β release.ConclusionsEA treatment relieves nerve injury-induced tactile allodynia and thermal hyperalgesia via the inhibition of P2X7R⁺ microglia-mediated IL-1β overexpression.

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