Glucocorticoid Receptor Contributes to Electroacupuncture-Induced Analgesia by Inhibiting Nav1.7 Expression in Rats With Inflammatory Pain Induced by Complete Freund's Adjuvant
Glucocorticoid Receptor Contributes to Electroacupuncture-Induced Analgesia by Inhibiting Nav1.7 Expression in Rats With Inflammatory Pain Induced by Complete Freund's Adjuvant
复制标题
糖皮质激素受体通过抑制弗氏完全佐剂诱导的炎症性疼痛大鼠中 Nav1.7 的表达来促进电针镇痛
DOI：
10.1111/ner.13499
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发表时间：
2021-08-02
期刊：
影响因子：
2.8
通讯作者：
Xu, Bo
中科院分区：
文献类型：
--
作者：
Luo, Huiying;Zhang, Yidan;Xu, Bo
背景：传统上电针治疗慢性疼痛，但其镇痛机制尚未完全阐明。我们在早期的研究中观察到，EA可以逆转炎性疼痛并抑制Nav1.7的高表达。然而，Nav1.7表达调控的分子机制尚不清楚。本研究旨在探讨糖皮质激素受体（GR）与Nav1.7之间的关系及其在电针镇痛中的作用。材料与方法本研究通过足底注射完全弗氏佐剂（CFA）建立大鼠炎性疼痛模型。电针刺激大鼠同侧“环跳”、“足三里”穴。蛋白质印迹，实时聚合酶链反应，免疫染色，鞘内注射，染色质免疫沉淀（ChIP）测定，以确定是否钠通道蛋白Nav1.7在CFA诱导的疼痛中发挥作用，以及是否GR调节Nav1.7的表达在镇痛EA刺激后。结果电针可显著降低热痛大鼠的缩足阈和热痛缩足潜伏期，抑制背根神经节GR和Nav1.7的表达。此外，治疗与GR正义寡核苷酸（OND）显着逆转这些变化。相反，用GR反义OND沿着EA应用的治疗产生更好的镇痛效果，这伴随着Nav1.7和GR蛋白表达的抑制。ChIP检测显示，GR与Nav1.7启动子的结合活性在CFA注射大鼠中增强，而在EA治疗大鼠中受到抑制。结论电针可通过抑制GR的表达而发挥抗炎性痛的作用，并可能通过调节Nav1. 7的表达而发挥抗炎性痛的作用。
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.