Background

While electroacupuncture (EA) has been used traditionally for the treatment of chronic pain, its analgesic mechanisms have not been fully clarified. We observed in an earlier study that EA could reverse inflammatory pain and suppress high Nav1.7 expression. However, the molecular mechanism underlying Nav1.7 expression regulation is unclear. In this study, we studied the relationship between the glucocorticoid receptor (GR) and Nav1.7 and the role of these molecules in EA analgesia.

Materials and Methods

In this study, we established an inflammatory pain model by intraplantar injection of complete Freund's adjuvant (CFA) in rats. EA stimulation was applied to the ipsilateral “Huantiao” (GB30) and “Zusanli” (ST36) acupoints in the rat model. Western blotting, real-time polymerase chain reaction, immunostaining, intrathecal injection, and chromatin immunoprecipitation (ChIP) assay were performed to determine whether the sodium channel protein Nav1.7 plays a role in CFA-induced pain and whether GR regulates Nav1.7 expression during analgesia following EA stimulation.

Results

EA application significantly decreased the paw withdrawal threshold thresholds and thermal paw withdrawal latency and suppressed GR and Nav1.7 expression in the dorsal root ganglion. Moreover, treatment with a GR sense oligonucleotide (OND) markedly reversed these alterations. In contrast, treatment with a GR antisense OND along with EA application exerted a better analgesic effect, which was accompanied by the suppression of Nav1.7 and GR protein expression. The ChIP assay showed that the binding activity of GR to the Nav1.7 promoter was enhanced in CFA injected rats and suppressed in EA-treated rats.

Conclusions

The present study demonstrated that EA exerted anti-hyperalgesic effects by inhibiting GR expression, which led to Nav1.7 expression modulation in the rat model of CFA-induced inflammatory pain.

中文翻译：

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糖皮质激素受体通过抑制完全弗氏佐剂诱导的炎症性疼痛大鼠的 Nav1.7 表达促进电针镇痛

背景

虽然电针 (EA) 传统上用于治疗慢性疼痛，但其镇痛机制尚未完全阐明。我们在早期的一项研究中观察到，EA 可以逆转炎症性疼痛并抑制 Nav1.7 的高表达。然而，Nav1.7 表达调控的分子机制尚不清楚。在这项研究中，我们研究了糖皮质激素受体 (GR) 和 Nav1.7 之间的关系以及这些分子在 EA 镇痛中的作用。

材料和方法

在这项研究中，我们通过在大鼠足底注射完全弗氏佐剂 (CFA) 建立了炎症性疼痛模型。电针刺激大鼠模型的同侧“环跳”(GB30) 和“足三里”(ST36) 穴位。进行蛋白质印迹、实时聚合酶链反应、免疫染色、鞘内注射和染色质免疫沉淀 (ChIP) 测定以确定钠通道蛋白 Nav1.7 是否在 CFA 诱导的疼痛中起作用以及 GR 是否调节 Nav1.7 表达在 EA 刺激后的镇痛期间。

结果

EA 应用显着降低了缩爪阈值阈值和热缩爪潜伏期，并抑制了背根神经节中的 GR 和 Nav1.7 表达。此外，用 GR 有义寡核苷酸 (OND) 治疗可显着逆转这些改变。相比之下，用 GR 反义 OND 与 EA 应用一起治疗可发挥更好的镇痛效果，同时抑制 Nav1.7 和 GR 蛋白表达。ChIP 测定表明，GR 与 Nav1.7 启动子的结合活性在注射 CFA 的大鼠中得到增强，而在 EA 处理的大鼠中受到抑制。

结论

本研究表明，EA 通过抑制 GR 表达发挥抗痛觉过敏作用，这导致 CFA 诱导的炎症性疼痛大鼠模型中的 Nav1.7 表达调节。