{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:56:46Z","timestamp":1791507406393,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"39","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20421"],"award-info":[{"award-number":["U23A20421"]}],"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":["32270871"],"award-info":[{"award-number":["32270871"]}],"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":["82201330"],"award-info":[{"award-number":["82201330"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neuropathic pain (NPP) is a critical clinical challenge with limited therapeutic options. While neuronal mechanisms have been extensively studied, the contribution of oligodendrocyte (OL) homeostasis to NPP pathogenesis is poorly understood. Here, we show that chronic constriction injury (CCI) causes demyelination and downregulation of 3\u2010phosphoinositide\u2010dependent kinase 1 (PDK1) in the central nervous system (CNS) in mice. Functional analysis of inducible OL lineage\u2010specific\n                    <jats:italic>Pdk1<\/jats:italic>\n                    conditional knockout (\n                    <jats:italic>Pdk1<\/jats:italic>\n                    cKO) mice reveals mechanical allodynia and thermal hyperalgesia,\u00a0a pattern of sensory changes that closely resembles NPP in CCI mice. RNA sequencing (RNA\u2010seq), morphological, and molecular analyses demonstrate that PDK1 deficiency impairs myelination via the c\u2010Myc\/SOX10 axis. Notably, pharmacological enhancement of remyelination or AAV\u2010mediated knockdown of c\u2010Myc restores nodal integrity and alleviates NPP in\n                    <jats:italic>Pdk1<\/jats:italic>\n                    cKO mice. Our findings establish PDK1\u2010mediated OL homeostasis as a critical determinant of NPP pathogenesis and identify c\u2010Myc modulation as a novel therapeutic strategy for NPP.\n                  <\/jats:p>","DOI":"10.1002\/advs.202516426","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T19:28:27Z","timestamp":1776367707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the PDK1\/c\u2010Myc\/SOX10 Signaling in Oligodendrocytes Alleviates Neuropathic Pain"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4270-9670","authenticated-orcid":false,"given":"Pingping","family":"Qiao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology Department of Neurosurgery Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Jiangsu Key Laboratory of Molecular Medicine Model Animal Research Center Medical School Nanjing University Nanjing China"},{"name":"Co\u2010innovation Center of Neuroregeneration Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Laser Surgery Hospital of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochao","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology Department of Neurosurgery Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Jiangsu Key Laboratory of Molecular Medicine Model Animal Research Center Medical School Nanjing University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1411-1417","authenticated-orcid":false,"given":"Chaoli","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Pain and Perioperative Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-9627","authenticated-orcid":false,"given":"Jian\u2010Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Pain and Perioperative Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4674-5548","authenticated-orcid":false,"given":"Guiquan","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology Department of Neurosurgery Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Jiangsu Key Laboratory of Molecular Medicine Model Animal Research Center Medical School Nanjing University Nanjing China"},{"name":"Co\u2010innovation Center of Neuroregeneration Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Hospital of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.06.017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lpm.2024.104232"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010024\u201001642\u20102"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23329"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.16206"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.84"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041\u2010020\u201000604\u20106"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhab428"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10123171"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00330"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2496\u201019.2020"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00230\u201016"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(88)90209\u20106"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2455\u201019.2021"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2146-22.2023"},{"key":"e_1_2_10_17_1","first-page":"299","article-title":"The Role of Oligodendrocytes in Chronic Pain: Cellular and Molecular Mechanisms","volume":"70","author":"Malta I.","year":"2019","journal-title":"Journal of Physiology and Pharmacology"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2016.03.005"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105212"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22648"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103756"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.01.051"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155276"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2008.03.016"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014\u20101158"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13751"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3296\u201008.2008"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3618"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002130"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010020\u201000905\u20107"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2025.1557214"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010024\u201003207\u20103"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac307"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419099112"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00399"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612822666151204000636"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6472"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhz146"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2023"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201014154\u20106"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201059849\u20101"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300060520903653"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23569"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003907"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.73673"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3390"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.70082"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2403652121"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402733101"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20335"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2023.102436"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.153166"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.20.040180.002301"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000172"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201004860\u20105"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.72144"},{"key":"e_1_2_10_57_1","article-title":"Stereotaxic Injection of a Viral Vector for Conditional Gene Manipulation in the Mouse Spinal Cord","volume":"18","author":"Inquimbert P.","year":"2013","journal-title":"Journal of Visualized Experiments: JoVE"},{"key":"e_1_2_10_58_1","first-page":"10","article-title":"Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin\u2010Induced Spinal Cord Demyelination in Mice","volume":"12","author":"Gu Z.","year":"2014","journal-title":"Journal of Neurology & Neurophysiology"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010024\u201003230\u20105"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202516426","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202516426","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202516426","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:38:03Z","timestamp":1783928283000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202516426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":58,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/advs.202516426"],"URL":"https:\/\/doi.org\/10.1002\/advs.202516426","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"assertion":[{"value":"2025-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e16426"}}