{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:36:03Z","timestamp":1792787763379,"version":"4.5.0"},"reference-count":58,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Key Program of the National Natural Science Foundation of China","award":["82130122"],"award-info":[{"award-number":["82130122"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["81973949"],"award-info":[{"award-number":["81973949"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82305049"],"award-info":[{"award-number":["82305049"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>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\u2019s 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-1\u03b2) in inflamed tissues. In a mouse model of complete Freund\u2019s 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-1\u03b2 levels in injured skin. Mirroring these effects, AICAR alone produced analgesia, increased autophagy, and lowered cytokine expression. Conversely, Compound C blocked EA\u2019s actions on autophagy and inflammatory markers, while 3-MA abrogated EA\u2019s analgesic and anti-inflammatory effects. Macrophage experiments corroborated the in vivo results, confirming that AMPK activation drives autophagy and subsequent suppression of iNOS\/IL-1\u03b2. Our findings establish a mechanistic axis whereby EA engages AMPK in macrophages to upregulate autophagy, which in turn curtails iNOS and IL-1\u03b2 production, ultimately mitigating inflammatory pain. This work unveils a novel cellular pathway for EA\u2019s anti-nociceptive effect and highlights AMPK-autophagy as a potential therapeutic target in pain management.<\/jats:p>","DOI":"10.1177\/17448069261491137","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:01:28Z","timestamp":1790683288000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Electroacupuncture alleviates inflammatory pain through AMPK-autophagy signaling and suppression of iNOS and IL-1\u03b2 in inflamed tissues"],"prefix":"10.1177","volume":"22","author":[{"given":"Hongchun","family":"Xiang","sequence":"first","affiliation":[{"name":"Huazhong University of Science and Technology"},{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4041-0437","authenticated-orcid":false,"given":"Man","family":"Li","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghong","family":"Jing","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Hu","sequence":"additional","affiliation":[{"name":"Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuye","family":"Lan","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongping","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weng","family":"Tao","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zou","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmin","family":"Liu","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0131-6434","authenticated-orcid":false,"given":"Xuefei","family":"Hu","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8444-3770","authenticated-orcid":false,"given":"Pan","family":"Hui-Lin","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cunzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Jing-Wen","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/aas.70055"},{"issue":"5","key":"e_1_3_5_3_2","first-page":"CD014585","article-title":"Proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug-induced ulcers and dyspepsia","volume":"5","author":"Garegnani L","year":"2025","unstructured":"Garegnani L, Oltra G, Burgos MA, et al. Proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug-induced ulcers and dyspepsia. Cochrane Database Syst Rev 2025; 5(5): CD014585. https:\/\/doi.org\/10.1002\/14651858.cd014585.pub2","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.47391\/JPMA.20349"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-026-04808-5"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.31348"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1450105"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000002005"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0208596"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2395"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070674"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175859"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01991-2"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm-22-5920"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1177\/09645284211028873"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1411-x"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-021-01593-x"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02524-9"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10081881"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1664705"},{"issue":"5","key":"e_1_3_5_21_2","first-page":"2922","article-title":"Electroacupuncture Alleviates CFA-Induced Inflammatory Pain via PD-L1\/PD-1-SHP-1 Pathway","volume":"60","author":"Deng D","year":"2023","unstructured":"Deng D, Xu F, Ma L, et al. Electroacupuncture Alleviates CFA-Induced Inflammatory Pain via PD-L1\/PD-1-SHP-1 Pathway. Mol Neurobiol 2023; 60(5): 2922\u20132936. https:\/\/doi.org\/10.1007\/s12035-023-03233-x","journal-title":"Mol Neurobiol"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep42531"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep22123"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)90144-9"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002648"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4571"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40487-022-00214-3"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6120"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1177\/1753425918771170"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.02.002"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1596481"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.109904"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002122"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/17448069231204051"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.09.010"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2023.113614"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3311"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjw043"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.10.077"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2023039"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.05.033"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-14-211"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053253"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.12.002"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109695"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-02056-0"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax6452"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2019.11.006"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0618-6"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-020-01399-x"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/8035109"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1069965"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07383"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.21599"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-36"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2012.089"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.55782\/ane-2022-006"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58851-x"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20192132"}],"container-title":["Molecular Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17448069261491137","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17448069261491137","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17448069261491137","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T08:26:08Z","timestamp":1791015968000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17448069261491137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":58,"alternative-id":["10.1177\/17448069261491137"],"URL":"https:\/\/doi.org\/10.1177\/17448069261491137","relation":{},"ISSN":["1744-8069","1744-8069"],"issn-type":[{"value":"1744-8069","type":"print"},{"value":"1744-8069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"article-number":"17448069261491137"}}