{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:41:59Z","timestamp":1786977719768,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Relationships between iron\u2010dependent ferroptosis and nerve system diseases have been recently revealed. However, the role of ferroptosis in neuropathic pain (NeP) remains to be elucidated. Thus, we aimed to investigate whether ferroptosis in spinal cord contributes to NeP induced by a chronic constriction injury (CCI) of the sciatic nerve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty Sprague\u2010Dawley rats received CCI or sham surgery, and were randomly assigned to the following four groups: sham group; CCI\u00a0+\u00a0LIP group; CCI\u00a0+\u00a0Veh group; and CCI group. Liproxstatin\u20101 or corn oil were separately injected intraperitoneally for three consecutive days after surgery in the CCI\u00a0+\u00a0LIP or CCI\u00a0+\u00a0Veh group. The mechanical and thermal hypersensitivities were tested after surgery. Biochemical and morphological changes related to ferroptosis in the spinal cord were also assessed. These included iron content, glutathione peroxidase 4 (GPX4) and anti\u2010acyl\u2010CoA synthetase long\u2010chain family member 4 (ACSL4) expression, lipid peroxidation assays, as well as mitochondrial morphology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CCI\u2010induced NeP was followed by iron accumulation, increased lipid peroxidation and dysregulation of ACSL4 and GPX4. Moreover transmission electron microscopy confirmed the presence of aberrant morphological changes on mitochondrial, such as mitochondria shrinkage and membrane rupture. Furthermore, the administration of liproxstatin\u20101 on CCI rats attenuated hypersensitivities, lowered the iron level, decreased spinal lipid peroxidation, restored the dysregulations in GPX4 and ACSL4 levels, and protected against CCI induced morphological changes in mitochondria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicated the involvement of ferroptosis in CCI induced NeP, and point to ferroptosis inhibitors such as liproxstatin\u20101 as potential therapies for hypersensitivity induced by peripheral nerve injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The spinal ferroptosis\u2010like cell death was involved in the development of neuropathic pain resulted from peripheral nerve injury, and inhibition of ferroptosis by liproxstatin\u20101 could alleviate mechanical and thermal hypersensitivities. This knowledge suggested that ferroptosis could represent a potential therapeutic target for neuropathic pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.1737","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T13:13:05Z","timestamp":1611666785000},"page":"1227-1240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Inhibition of ferroptosis\u2010like cell death attenuates neuropathic pain reactions induced by peripheral nerve injury in rats"],"prefix":"10.1002","volume":"25","author":[{"given":"Yue","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuicui","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Medical Quality Management Nanfang Hospital Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqing","family":"Hei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Third Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ner.12620"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010818-021524"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90209-6"},{"key":"e_1_2_8_5_1","first-page":"7494821","article-title":"Expression of duodenal iron transporter proteins in diabetic patients with and without iron deficiency","volume":"2018","author":"Broide E.","year":"2018","journal-title":"Anemia Journal of Diabetes Research"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00539"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20191511"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.03.067"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135531"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-00556-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.5b00245"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2239"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.10.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3064"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.09.043"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00214"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806919847366"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2019.03.005"},{"key":"e_1_2_8_20_1","article-title":"Inhibition of ferroptosis attenuates acute kidney injury in rats with severe acute pancreatitis","author":"Ma D.","year":"2020","journal-title":"Digestive Diseases and Sciences"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051651"},{"issue":"10","key":"e_1_2_8_22_1","first-page":"CD010902","article-title":"Oral nonsteroidal anti\u2010inflammatory drugs for neuropathic pain","volume":"2015","author":"Moore R. 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