Electroacupuncture alleviates inflammatory pain through AMPK-autophagy signaling and suppression of iNOS and IL-1β in inflamed tissues
6 affiliations
- 1Department of Acupuncture-moxibustion, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
- 2Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
- 3Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China
- 4Department of Pharmacology, School of Basic Medicine, Nanjing Medical University, Nanjing, Jiangsy, China
- 5International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
- 6Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Abstract
Electroacupuncture (EA) effectively alleviates inflammatory pain, yet its underlying mechanisms remain incompletely understood. Emerging evidence implicates AMP-activated protein kinase (AMPK) and autophagy in modulating inflammation, but whether they mediate EA’s analgesic action is unknown. This study tests the hypothesis that EA relieves inflammatory pain by activating AMPK in macrophages, thereby triggering autophagy and suppressing pro-inflammatory mediators (iNOS and IL-1β) in inflamed tissues. In a mouse model of complete Freund’s adjuvant (CFA)-induced inflammatory pain, we assessed pain behavior and inflammatory markers following EA. Pharmacological modulators- AMPK antagonist Compound C, AMPK activator AICAR, and autophagy inhibitor 3-methyladenine (3-MA) - were applied to dissect the AMPK- autophagy-cytokine cascade. Complementary in vitro experiments using NR8383 macrophages with a autophagy reporter (stubRFP-sensGFP-LC3 Lentivirus) further validated the pathway. EA not only reduced CFA-induced hyperalgesia but also concurrently augmented AMPK phosphorylation, enhanced autophagic flux, and diminished iNOS and IL-1β levels in injured skin. Mirroring these effects, AICAR alone produced analgesia, increased autophagy, and lowered cytokine expression. Conversely, Compound C blocked EA’s actions on autophagy and inflammatory markers, while 3-MA abrogated EA’s analgesic and anti-inflammatory effects. Macrophage experiments corroborated the in vivo results, confirming that AMPK activation drives autophagy and subsequent suppression of iNOS/IL-1β. Our findings establish a mechanistic axis whereby EA engages AMPK in macrophages to upregulate autophagy, which in turn curtails iNOS and IL-1β production, ultimately mitigating inflammatory pain. This work unveils a novel cellular pathway for EA’s anti-nociceptive effect and highlights AMPK-autophagy as a potential therapeutic target in pain management.
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BibTeX
@article{xiang2026electroacupuncture,
title = {{Electroacupuncture alleviates inflammatory pain through AMPK-autophagy signaling and suppression of iNOS and IL-1β in inflamed tissues}},
author = {Hongchun Xiang and Man Li and Xianghong Jing and Liang Hu and Yuye Lan and Hongping Li and Weng Tao and Yan Zou and Yongmin Liu and Xuefei Hu and Hong Zhang and Pan Hui-Lin and Wentao Liu and Cunzhi Liu and Nana Yang and Yang Jing-Wen and Jing Li},
journal = {Molecular Pain},
year = {2026},
month = sep,
doi = {10.1177/17448069261491137},
url = {https://doi.org/10.1177/17448069261491137},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Electroacupuncture alleviates inflammatory pain through AMPK-autophagy signaling and suppression of iNOS and IL-1β in inflamed tissues
AU - Hongchun Xiang
AU - Man Li
AU - Xianghong Jing
AU - Liang Hu
AU - Yuye Lan
AU - Hongping Li
AU - Weng Tao
AU - Yan Zou
AU - Yongmin Liu
AU - Xuefei Hu
AU - Hong Zhang
AU - Pan Hui-Lin
AU - Wentao Liu
AU - Cunzhi Liu
AU - Nana Yang
AU - Yang Jing-Wen
AU - Jing Li
PY - 2026
DA - 2026/09/29
JO - Molecular Pain
DO - 10.1177/17448069261491137
UR - https://doi.org/10.1177/17448069261491137
AB - Electroacupuncture (EA) effectively alleviates inflammatory pain, yet its underlying mechanisms remain incompletely understood. Emerging evidence implicates AMP-activated protein kinase (AMPK) and autophagy in modulating inflammation, but whether they mediate EA’s analgesic action is unknown. This study tests the hypothesis that EA relieves inflammatory pain by activating AMPK in macrophages, thereby triggering autophagy and suppressing pro-inflammatory mediators (iNOS and IL-1β) in inflamed tissues. In a mouse model of complete Freund’s adjuvant (CFA)-induced inflammatory pain, we assessed pain behavior and inflammatory markers following EA. Pharmacological modulators- AMPK antagonist Compound C, AMPK activator AICAR, and autophagy inhibitor 3-methyladenine (3-MA) - were applied to dissect the AMPK- autophagy-cytokine cascade. Complementary in vitro experiments using NR8383 macrophages with a autophagy reporter (stubRFP-sensGFP-LC3 Lentivirus) further validated the pathway. EA not only reduced CFA-induced hyperalgesia but also concurrently augmented AMPK phosphorylation, enhanced autophagic flux, and diminished iNOS and IL-1β levels in injured skin. Mirroring these effects, AICAR alone produced analgesia, increased autophagy, and lowered cytokine expression. Conversely, Compound C blocked EA’s actions on autophagy and inflammatory markers, while 3-MA abrogated EA’s analgesic and anti-inflammatory effects. Macrophage experiments corroborated the in vivo results, confirming that AMPK activation drives autophagy and subsequent suppression of iNOS/IL-1β. Our findings establish a mechanistic axis whereby EA engages AMPK in macrophages to upregulate autophagy, which in turn curtails iNOS and IL-1β production, ultimately mitigating inflammatory pain. This work unveils a novel cellular pathway for EA’s anti-nociceptive effect and highlights AMPK-autophagy as a potential therapeutic target in pain management.
SN - 1744-8069
ER -