{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:35:52Z","timestamp":1784295352221,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neuropathic pain (NP) is a challenging health condition owing to its complex nature and associated multiple etiologies. The occurrence of NP involves the abnormal activity of neurons mediated by oxidative stress (OS). Previous research has demonstrated that m6A methylation plays a role in the regulatory pathway of NP. This study aimed to investigate the specific molecular pathways through which m6A methylation modifiers alleviate NP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For this purpose, an NO rat model was developed via spared nerve injury (SNI), followed by quantifying the animal's pain assessment via paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The OS in SNI rats was evaluated by measuring reactive oxygen species, superoxide dismutase, and catalase (CAT) in spinal cord tissues. Moreover, quantitative\u2010real\u2010time polymerase chain reaction and western blot analysis were employed for detecting fat mass and obesity\u2010associated (FTO) and GPR177 levels, while m6A levels of GPR117 were analyzed via MeRIP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results indicated an enhanced OS with highly expressed FTO in spinal cord tissue samples, where knocking down <jats:italic>Fto<\/jats:italic> effectively relieved NP and OS in SNI rats. Mechanistic investigations revealed that <jats:italic>Fto<\/jats:italic>\u2010mediated reduction of <jats:italic>Grp177<\/jats:italic> m6A modification was involved in the WNT5a\/TRPV1 axis\u2010mediated OS remission of NP. Moreover, in vitro experiment results indicated that YTHDF2 was an important m6A methylated reading protein for this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>Fto<\/jats:italic> silencing leads to increased m6A methylation of <jats:italic>Grp177<\/jats:italic> through a YTHDF2\u2010dependent mechanism, resulting in decreased <jats:italic>Grp177<\/jats:italic> stability and ultimately reducing NP in rats by OS suppression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.1345","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T14:05:10Z","timestamp":1721311510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Silencing of FTO inhibits oxidative stress to relieve neuropathic pain by m6A modification of 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