目的:本研究探讨电针(EA)对急性术后疼痛(APP)的影响及干扰素基因/1型干扰素(STING/IFN-1)信号通路刺激因子在EA对APP大鼠镇痛作用中的作用。
方法:通过腹部手术启动APP大鼠模型,动物在双侧ST36(足三里)和SP6(三阴交)穴位接受两次30分钟的EA治疗。机械,进行热和冷敏感性测试以测量疼痛阈值,在初级体感皮层记录脑电图,以确定EA治疗对APP的影响。使用蛋白质印迹和免疫荧光检查STING/IFN-1途径中蛋白质的表达和分布以及神经炎症。鞘内施用STING抑制剂(C-176)以验证其在EA中的作用。
结果:与对照组相比,APP大鼠表现出机械和热超敏反应(P<0.05)。APP显著降低了θ的振幅,α和γ振荡与其基线值相比(P<0.05)。有趣的是,诱导APP后,STING/IFN-1通路蛋白表达水平下调(P<0.05)。Further,APP增加促炎因子,包括白细胞介素-6、肿瘤坏死因子-α和诱导型一氧化氮合酶,和下调的抗炎因子,白细胞介素-10和精氨酸酶-1(P<0.05)。EA有效减轻APP引起的疼痛性超敏反应(P<0.05)并恢复了θ,APP大鼠的α和γ功率(P<0.05)。同时,EA明显激活STING/IFN-1途径并减轻神经炎症反应(P<0.05)。此外,STING/IFN-1主要在isolectin-B4-或降钙素基因相关肽标记的背根神经节神经元和脊髓背角浅层中表达。鞘内注射C-176对STING/IFN-1通路的抑制作用减弱了EA对APP的镇痛和抗炎作用(P<0.05)。
结论:EA可以对APP产生强大的镇痛和抗炎作用,这些作用可能与激活STING/IFN-1途径有关,提示STING/IFN-1可能是缓解APP的靶标。请引用这篇文章为:丁YY,徐F,王YF,HanLL,黄SQ,赵S,妈,张思,赵WJ,陈XD。电针通过刺激干扰素基因/1型干扰素通路抑制神经炎症减轻术后疼痛。JIntegrMed。2023年;Epub领先于印刷。
This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats.
The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA.
APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05).
EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.