{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:48:01Z","timestamp":1791910081984,"version":"4.3.4"},"reference-count":37,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroimmunomodulation"],"abstract":"<jats:p>Introduction: Neuropathic pain is associated with hypoxia, inflammation, and metabolic dysregulation, in which hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) plays a key regulatory role. This study investigates whether phosphoinositide 3-kinase (PI3K) inhibition by taselisib alleviates neuropathic pain via suppression of HIF-1\u03b1-mediated pathological signaling. Methods: In this study, a rat model of chronic constriction injury (CCI) was used to investigate whether neuropathic pain could be alleviated by taselisib, a selective PI3K inhibitor. Taselisib was administered daily, with or without co-administration of dimethyloxalylglycine (DMOG), a HIF-1\u03b1 activator. Mechanical allodynia and thermal hyperalgesia were evaluated using behavioral tests. mRNA level in the dorsal root ganglia (DRG) was quantified by RT-qPCR, whereas protein levels were assessed by Western blotting, immunofluorescence, and metabolic assays were performed to assess angiogenesis, glycolytic activity, and inflammatory responses. Results: Taselisib significantly alleviated mechanical allodynia and thermal hyperalgesia in CCI rats, effects that were attenuated by co-administration of the HIF-1\u03b1 activator DMOG. Taselisib suppressed CCI-induced upregulation of HIF-1\u03b1 in DRG at both transcript and protein levels, and this suppression was reversed by DMOG. Downstream targets of HIF-1\u03b1, including mTOR, VEGFA, GLUT1, PFKM, and PDK1, were similarly downregulated by taselisib and partially restored upon HIF-1\u03b1 activation. Metabolically, taselisib reduced lactate accumulation and restored ATP levels, indicating inhibition of glycolytic reprogramming. Taselisib also attenuated systemic and DRG-localized inflammatory responses, including IL-6, IL-1\u03b2, and NF-\u03baB p65 expression; these anti-inflammatory effects were mitigated by DMOG. Conclusion: Taselisib alleviates neuropathic pain by disrupting HIF-1\u03b1-mediated angiogenic, inflammatory, and metabolic signaling. Targeting the PI3K-HIF-1\u03b1 axis offers a promising therapeutic approach.<\/jats:p>","DOI":"10.1159\/nim\/adxag005","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:27:04Z","timestamp":1788521224000},"page":"360-371","source":"Crossref","is-referenced-by-count":0,"title":["Taselisib, a PI3K Inhibitor, Alleviates Neuropathic Pain through HIF-1\u03b1-Mediated Angiogenesis in a Rat Model of Chronic Constriction Injury"],"prefix":"10.1159","volume":"33","author":[{"given":"Hai-Ping","family":"You","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Hong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chui-Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He-Fan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Yuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Geng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Feng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong-Jun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114693"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002850"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2025.03.006"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1367994"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.31083\/JIN25829"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics14192167"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2023.07.007"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003332"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14246054"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103316"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2024.106541"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1155\/prm\/9923147"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-04254-w"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.02.027"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-023-02306-7"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00941-3"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175858"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-025-02173-4"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1002\/syn.22125"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2023.110671"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.77304"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203997"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119615"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1159\/000455987"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01497-x"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1177\/1744806919850043"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2018.05.039"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.121201"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1515\/tnsci-2016-0008"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17303"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02765-2"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-025-05608-w"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.36.22642"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059796"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059817"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.10.020"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58482-w"}],"container-title":["Neuroimmunomodulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/nim\/adxag005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:01:15Z","timestamp":1791907275000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/nim\/adxag005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1159\/nim\/adxag005","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.33405913","asserted-by":"subject"}]},"ISSN":["1021-7401","1423-0216"],"issn-type":[{"value":"1021-7401","type":"print"},{"value":"1423-0216","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}