Electroacupuncture ameliorates inflammatory pain through CB2 receptor-dependent activation of the AMPK signaling pathway

作者：Yuye Lan, Xiang‐Hong Jing, Ziyu Zhou, Yiqing Rao, Kaichen Wang, Renjie Qin, Yuming Wu, Jingjing Sun, Ke Zhang, Xinyue Liu, Zixiao Wang, Jiahao Xu, Minzhen zhao, Xiao Yuan, Yongmin Liu, Hong Zhang, Xuefei Hu, Hui‐Lin Pan, Tengfei Hou, Man Li · 发表于：Chinese Medicine · 年份：2024 · DOI：10.1186/s13020-024-01048-z · 被引用次数：16 · 研究领域：Pain Mechanisms and Treatments、Acupuncture Treatment Research Studies、Cannabis and Cannabinoid Research

BACKGROUND: Chronic inflammatory pain is a pervasive condition, and electroacupuncture (EA) is an effective treatment, but its mechanisms are not fully understood. AMP-activated protein kinase (AMPK), a key energy sensor, is involved in pain relief and EA's effects. EA may work by increasing endocannabinoids, upregulating CB2 receptors (CB2R), and stimulating β-endorphin (β-END). This study tests if EA activates AMPK via CB2R to modulate β-END and reduce pain. METHODS: The inflammatory pain model was established with Complete Freund's adjuvant (CFA), and EA was administered daily for six consecutive days, targeting the acupoints "Zusanli" (ST36) and "Shangjuxu" (ST37). Pain sensitivity was evaluated using Von Frey filaments for mechanical thresholds and a hot plate for thermal thresholds. Ultra-high Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) was used to quantitatively determine the levels of endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA). The expression levels of the CB2R and β-END were measured by Western blotting, along with the activation of AMPK. Immunofluorescence double-labeling was applied to visualize AMPK activation and β-END expression within CD68-positive macrophages. The study encompassed both wild-type and CB2R gene knockout mice, elucidating the role of CB2R in EA-induced AMPK activation. RESULTS: CFA-induced inflammatory pain model mice exhibited mechanical allodynia and thermal hyperalgesia. EA activated AMPK i...