Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Electroacupuncture; Inflammation; Pain; Primary sensory neurons; Stimulator of interferon genes; Type-1 interferon.