Inflammatory pain, the most prevalent disease globally, remains challenging to manage. Electroacupuncture emerges as an effective therapy, yet its underlying mechanisms are not fully understood. This study investigates whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-regulated silent information regulator 1 (SIRT1) contributes to electroacupuncture's antinociceptive effects by modulating macrophage/microglial polarization in the spinal dorsal horn of a mouse model of inflammatory pain. In this study, mice, introduced to inflammatory pain through subcutaneous injections of complete freund's adjuvant (CFA) in the plantar area, underwent electroacupuncture therapy every alternate day for 30-min sessions. The assessment of mechanical allodynia and thermal hyperalgesia in these subjects was carried out using paw withdrawal frequency and paw withdrawal latency measurements, respectively. Western blot analysis measured levels of AMPK, phosphorylation-adenosine 5'-monophosphate (AMP)-activated protein kinase, SIRT1, inducible nitric oxide synthase, cluster of differentiation 86, arginase 1, and interleukin 10. In contrast to the group treated solely with CFA, the cohort receiving both CFA and electroacupuncture demonstrated notable decreases in both thermal hyperalgesia and mechanical allodynia. This was accompanied by a marked enhancement in AMPK phosphorylation levels. AMPK knockdown reversed electroacupuncture's analgesic effects and reduced M2 macrophage/microglial polarization enhancement. Additionally, AMPK knockdown significantly weakened electroacupuncture-induced SIRT1 upregulation, and EX-527 injection attenuated electroacupuncture's facilitation of M2 macrophage/microglial polarization without affecting AMPK phosphorylation levels. Furthermore, combining electroacupuncture with SRT1720 enhanced the analgesic effect of SRT1720. Our findings suggest that AMPK regulation of SIRT1 plays a critical role in electroacupuncture's antinociceptive effect through the promotion of M2 macrophage/microglial polarization.

中文翻译：

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电针促进巨噬细胞/小胶质细胞 M2 极化并通过 AMPK 抑制炎性疼痛。

炎症性疼痛是全球最常见的疾病，治疗起来仍然具有挑战性。电针作为一种有效的疗法出现，但其潜在机制尚不完全清楚。本研究探讨了腺苷 5'-单磷酸 (AMP) 激活蛋白激酶 (AMPK) 调节的沉默信息调节因子 1 (SIRT1) 是否通过调节炎症小鼠模型脊髓背角中的巨噬细胞/小胶质细胞极化来促进电针的镇痛作用疼痛。在这项研究中，通过在足底皮下注射完全弗氏佐剂 (CFA) 使小鼠产生炎性疼痛，每隔一天接受一次 30 分钟的电针治疗。分别使用缩爪频率和缩爪潜伏期测量来评估这些受试者的机械异常性疼痛和热痛觉过敏。蛋白质印迹分析测量了 AMPK、磷酸化腺苷 5'-单磷酸 (AMP) 激活蛋白激酶、SIRT1、诱导型一氧化氮合酶、分化簇 86、精氨酸酶 1 和白细胞介素 10 的水平。 CFA，同时接受 CFA 和电针治疗的队列显示热痛觉过敏和机械异常性疼痛均显着减少。伴随着 AMPK 磷酸化水平的显着增强。 AMPK 敲低可逆转电针的镇痛作用并减少 M2 巨噬细胞/小胶质细胞极化增强。此外，AMPK 敲低显着削弱了电针诱导的 SIRT1 上调，而 EX-527 注射减弱了电针对 M2 巨噬细胞/小胶质细胞极化的促进作用，而不影响 AMPK 磷酸化水平。此外，电针与SRT1720的结合增强了SRT1720的镇痛效果。我们的研究结果表明，SIRT1 的 AMPK 调节通过促进 M2 巨噬细胞/小胶质细胞极化，在电针的镇痛作用中发挥着关键作用。