{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:40:21Z","timestamp":1777635621161,"version":"3.51.4"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":117,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011833","name":"Guangxi University of Chinese Medicine","doi-asserted-by":"publisher","award":["2025QN023"],"award-info":[{"award-number":["2025QN023"]}],"id":[{"id":"10.13039\/501100011833","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060902"],"award-info":[{"award-number":["82060902"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260961"],"award-info":[{"award-number":["82260961"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82505721"],"award-info":[{"award-number":["82505721"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pain Research and Management"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuropathic pain (NP) has become a major global public health issue. Tuina, a traditional therapy, has been shown to alleviate pain effectively by promoting nerve repair and reducing neuroinflammation. This study aimed to investigate whether Tuina can suppress the ferroptosis\u2010autophagy pathway to improve NP induced by spinal nerve ligation (SNL) in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 42 Sprague\u2010Dawley rats were randomly allocated into seven experimental groups, with six rats in each group: Sham, SNL model, SNL\u2009+\u2009Sham Tuina, SNL\u2009+\u2009Tuina (acupoints GB30\/GB34\/GB39, 5\u2009N pressure, 120\u2009times\/min, 18\u2009min\/day for 14\u2009days), SNL\u2009+\u2009si\u2010NC (empty vector), SNL\u2009+\u2009si\u2010NCOA4 (NCOA4 silencing), and SNL\u2009+\u2009ferrostatin\u20101 (10\u2009mg\/kg for 7\u2009days). Pain behaviors were assessed using paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Protein expressions of NCOA4, ferritin heavy chain 1 (FTH1), microtubule\u2010associated protein 1 light chain 3 (LC3), glutathione peroxidase 4 (GPX4), and acyl\u2010CoA synthetase long\u2010chain family member 4 (ACSL4) were detected by the western blot. Immunofluorescence visualized NCOA4\u2010FTH1 colocalization. The mitochondrial ultrastructure was analyzed by TEM. Fe\n                      <jats:sup>2+<\/jats:sup>\n                      and MDA levels were measured colorimetrically.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with the SNL\u2009+\u2009Sham group, the Tuina group exhibited a significantly increased PWT (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) and PWL (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). IHC analysis revealed that the Tuina intervention reduced the proportion of NCOA4\u2010positive cells (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), increased GPX4 expression (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), and decreased ACSL4 expression (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) in the spinal dorsal horn. Western blot further confirmed that Tuina downregulated NCOA4, LC3, and ACSL4 protein levels (all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), while upregulating FTH1 and GPX4 (both\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). IF demonstrated enhanced colocalization of NCOA4 and FTH1 in the Tuina group (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). TEM observations indicated that Tuina ameliorated ferroptosis\u2010associated mitochondrial damage, including cristae disruption and membrane rupture. Biochemical assays showed that Tuina significantly reduced the spinal cord Fe\n                      <jats:sup>2+<\/jats:sup>\n                      content (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) and MDA levels (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tuina alleviates NP in SNL rats, an effect correlated with the inhibition of NCOA4\u2010mediated ferritinophagy, decreased iron overload and lipid peroxidation, and attenuated ferroptosis in spinal dorsal horn neurons.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/prm\/6673176","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:30:33Z","timestamp":1777440633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tuina Analgesia Is Associated With the Modulation of the NCOA4\u2010Mediated Ferroautophagy\u2013Ferroptosis Pathway in SNL\u2010Induced Neuropathic Pain Rats"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-9107","authenticated-orcid":false,"given":"Kailong","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5863-2710","authenticated-orcid":false,"given":"Peipei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3078-0836","authenticated-orcid":false,"given":"Xiaofeng","family":"Gan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7761-5605","authenticated-orcid":false,"given":"Hongliang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8595-6226","authenticated-orcid":false,"given":"Liangyuan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6586-2408","authenticated-orcid":false,"given":"Yueqiang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001939"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2023.04.021"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108546"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lpm.2024.104233"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.672498"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1206851"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13197-021-05184-4"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/17590914221133236"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.12.001"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1383203"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48151-1"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-024-02758-2"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2025.07.001"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03463-z"},{"key":"e_1_2_11_15_2","article-title":"Electroacupuncture Regulates Neuronal Ferroptosis and Ferritinophagy Through lysosomal-mediated TFEB Activation in Cerebral ischemia-reperfusion","author":"Tang B.","year":"2025","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctim.2024.103068"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6652099"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1096734"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8309745"},{"key":"e_1_2_11_20_2","article-title":"Clinical Observation on Acupuncture Treatment of Piriformis syndrome","volume":"23","author":"Shu H. 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