Department of Anesthesiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 185, Pu An Road, Shanghai, 201203, China.
Neurochem Res. 2024 May;49(5):1268-1277. doi: 10.1007/s11064-024-04114-y. Epub 2024 Feb 10.
Electroacupuncture (EA) effectively improves arthritis-induced hyperalgesia and allodynia by repressing spinal microglial activation, which plays a crucial role in pain hypersensitivity following tissue inflammation. However, the mechanism by which EA suppresses spinal microglial activation in monoarthritis (MA) remains unclear. In the present study, a rat model of MA was established through unilateral ankle intra-articular injection of complete Freund's adjuvant (CFA). The relationship among P2Y12 receptor (P2Y12R) expression, spinal microglial activation, and EA analgesia was investigated using quantitative real-time PCR (qRT‒PCR), western blotting, immunofluorescence (IF), and behavioral testing. The results found that EA treatment at the ipsilateral "Huantiao" (GB30) and "Yanglingquan" (GB34) acupoints markedly attenuated pain and spinal microglia M1 polarization in MA rats. In particular, P2Y12R expression was significantly increased at the mRNA and protein levels in the spinal dorsal horn in MA rats, whereas EA treatment effectively repressed the MA-induced upregulation of P2Y12R. IF analysis further revealed that most P2Y12R was expressed in microglia in the spinal dorsal horn. Pharmacological inhibition of P2Y12R by its antagonist (AR-C69931MX) decreased MA-induced spinal microglial activation and subsequent proinflammatory cytokine production. Consequently, AR-C69931MX significantly intensified the anti-pain hypersensitive function of EA in MA rats. Taken together, these results demonstrate that EA alleviates MA-induced pain by suppressing P2Y12R-dependent microglial activation.
电针（EA）通过抑制脊髓小胶质细胞激活有效改善关节炎引起的痛觉过敏和感觉异常，而脊髓小胶质细胞激活在组织炎症后疼痛敏化中起关键作用。然而，EA 抑制单关节炎（MA）中脊髓小胶质细胞激活的机制尚不清楚。在本研究中，通过单侧踝关节关节内注射完全弗氏佐剂（CFA）建立 MA 大鼠模型。使用定量实时 PCR（qRT-PCR）、western blot、免疫荧光（IF）和行为测试研究 P2Y12 受体（P2Y12R）表达、脊髓小胶质细胞激活与 EA 镇痛之间的关系。结果发现，在 MA 大鼠中，对同侧“环跳”（GB30）和“阳陵泉”（GB34）穴位进行 EA 治疗可显著减轻疼痛和脊髓小胶质细胞 M1 极化。特别是，在 MA 大鼠脊髓背角中 P2Y12R 的 mRNA 和蛋白水平均显著增加，而 EA 治疗可有效抑制 MA 诱导的 P2Y12R 上调。IF 分析进一步表明，脊髓背角中的大多数 P2Y12R 表达于小胶质细胞中。其拮抗剂（AR-C69931MX）对 P2Y12R 的药理抑制作用可降低 MA 诱导的脊髓小胶质细胞激活和随后的促炎细胞因子产生。因此，AR-C69931MX 显著增强了 MA 大鼠中 EA 的抗痛觉过敏功能。综上所述，这些结果表明 EA 通过抑制 P2Y12R 依赖性小胶质细胞激活缓解 MA 诱导的疼痛。
