The Analgesic Effect of NLRP3 Inflammasome in the Relief of Inflammatory Pain by Electroacupuncture: A Systematic Review and Meta-Analysis of Animal Studies

Abstract

Ruisi Su,1,* Zhefeng Wang,1,* Guodong Zhang,2 Yinghui Tao,1 Haonan Zhu,1 Haibo Chen,2 Jiaying Li,2 Zhichao Sun2 1The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhichao Sun; Jiaying Li, Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), 54 Youdian Road, Hangzhou, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]; [email protected]: Inflammatory pain originates from the inflammatory response triggered by tissue injury, accompanied by the release of pro-inflammatory mediators. NLRP3 inflammasome, as a key innate immune receptor, plays a central role in inflammatory pain. Electroacupuncture (EA) is a commonly used analgesic method in clinical practice. Its anti-inflammatory mechanism involves regulating neural-immune interaction, regulating the balance of pro-inflammatory/anti-inflammatory cytokines, and inhibiting the NF-κB pathway. However, whether EA can alleviate inflammatory pain by specifically inhibiting NLRP3 inflammasome activation and its downstream signaling pathways is still unclear.Purpose: This study aims to evaluate the analgesic effects of electroacupuncture on inflammatory pain, focusing on inflammatory cytokines and NLRP3-related signaling pathways to elucidate the underlying mechanisms.Methods: Studies that meet the inclusion and exclusion criteria were selected by searching PubMed, EMBASE, Cochrane, and Web of Science databases. To evaluate the quality of each included study using the modified 10-item checklist from the Collaboration for the Advancement of Meta-analysis in Animal Research. After extracting the relevant data, perform a meta-analysis using RevMan software.Results: A total of 10 studies were included. The results of the meta-analysis indicated that electroacupuncture treatment increased the heat pain threshold [− 2.74 (95% CI − 3.50 ~ − 1.98)] and mechanical pain threshold [− 2.89 (95% CI − 3.59 ~ − 2.20)]. Electroacupuncture reduced the levels of pro-inflammatory cytokines IL-1β, IL-18, IL-6, IL-12, IL-17, TNF-α, and PGE2, and increased the levels of anti-inflammatory cytokines IL-10. This study found that EA mainly regulated NLRP3 related signaling pathway through ROS, P2X7R and other pathways, thereby reducing the expression of NLRP3 inflammasome. Subgroup analysis of CFA-induced inflammatory pain showed that EA reduced inflammatory pain by regulating NLRP3 inflammasome.Conclusion: Electroacupuncture may alleviate inflammatory pain by modulating inflammatory cytokines and regulating the NLRP3 signaling pathway, which could help reduce the use of analgesic medications.Keywords: animal model, electroacupuncture, inflammatory pain, meta-analysis, NLRP3

Keywords

• Animal Model
• Electroacupuncture
• Inflammatory pain
• Meta-Analysis
• NLRP3