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Here, we found that upregulation of transcription factor NFATc2 decreased the expression of Beclin-1, a critical molecule in autophagy, in the spinal dorsal horn, and contributed to neuropathic pain following oxaliplatin treatment. Meanwhile, manipulating autophagy levels by intrathecal injection of rapamycin (RAPA) or 3-methyladenine (3-MA) differentially altered mechanical allodynia in oxaliplatin-treated or na\u00efve rats. Utilizing chromatin immunoprecipitation-sequencing (ChIP-seq) assay combined with bioinformatics analysis, we found that NFATc2 negatively regulated the transcription of tuberous sclerosis complex protein 2 (TSC2), which contributed to the oxaliplatin-induced Beclin-1 downregulation. Further assays revealed that NFATc2 regulated histone H4 acetylation and methylation in the TSC2 promoter site 1 in rats\u2019 dorsal horns with oxaliplatin treatment. These results suggested that NFATc2 mediated the epigenetic downregulation of the TSC2\/Beclin-1 autophagy pathway and contributed to oxaliplatin-induced mechanical allodynia, which provided a new therapeutic insight for chemotherapy-induced neuropathic pain.<\/jats:p>","DOI":"10.1177\/17448069231158289","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T01:33:31Z","timestamp":1675388011000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["NFATc2-dependent epigenetic downregulation of the TSC2\/Beclin-1 pathway is involved in neuropathic pain induced by oxaliplatin"],"prefix":"10.1177","volume":"19","author":[{"given":"Meng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesia and Pain Medicine, Guangzhou First People\u2019s Hospital, Guangzhou, 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