{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:27:13Z","timestamp":1788276433960,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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":["82071237"],"award-info":[{"award-number":["82071237"]}],"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":["82401437"],"award-info":[{"award-number":["82401437"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515010147"],"award-info":[{"award-number":["2023A1515010147"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2026A1515012403"],"award-info":[{"award-number":["2026A1515012403"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2026A1515011172"],"award-info":[{"award-number":["2026A1515011172"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515011180"],"award-info":[{"award-number":["2023A1515011180"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Chemotherapy\u2010induced peripheral neuropathy (CIPN) lacks disease\u2010modifying therapies, and how epitranscriptomic regulation drives central sensitization remains unclear. In the present study focusing on paclitaxel\u2010induced peripheral neuropathy (PIPN), we identified a METTL3\u2013circRNA axis in the spinal dorsal horn wherein upregulated METTL3 expanded the m6A\u2010modified circMtmr7 pool in paclitaxel\u2010treated mice. Accordingly in paclitaxel\u2010treated mice,\u00a0upregulated METTL3 paralleled elevated m6A\u2010circMtmr7 expression; METTL3 knockdown prevented the paclitaxel\u2010evoked rise in m6A\u2010circMtmr7, normalized miniature excitatory postsynaptic current (EPSC) amplitude and frequency, as well as neuronal firing rates, and alleviated mechanical allodynia. Mechanistically\n                      <jats:italic>circMtmr7<\/jats:italic>\n                      operated via two convergent branches to upregulate the effector NUFIP2: (i) in the cytoplasm it served as a microRNA (miRNA) sponge for miR\u20107010\u20105p, miR\u20103057\u20105p and miR\u201026b\u20103p, relieving repression and increasing NUFIP2; (ii) in the nucleus it associated with STAT5A to enhance NUFIP2 transcription, and silencing STAT5A reversed neuronal hyperexcitability and attenuated nociceptive behaviours. Genetic or pharmacological manipulation of METTL3,\n                      <jats:italic>circMtmr7<\/jats:italic>\n                      , STAT5A or NUFIP2 bidirectionally modulated neuronal excitability and nociceptive hypersensitivity. Collectively these data establish an m6A\u2010dependent writer\u2010circRNA\u2010transcription factor hub that couples post\u2010transcriptional and transcriptional programmes to amplify excitatory drive in PIPN, suggesting that STAT5A and NUFIP2 represent candidate targets for therapeutic development.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70768-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            In paclitaxel\u2010treated mice, spinal dorsal horn METTL3 is upregulated, expanding the m6A\u2010modified\n                            <jats:italic>circMtmr7<\/jats:italic>\n                            pool to drive central sensitization in paclitaxel\u2010induced peripheral neuropathy.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>circMtmr7 convergently upregulates NUFIP2 by acting as a cytoplasmic microRNA (miRNA) sponge and by associating with nuclear STAT5A to enhance transcription, thereby amplifying neuronal excitability.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Pharmacological or genetic inhibition of METTL3,\n                            <jats:italic>circMtmr7<\/jats:italic>\n                            , STAT5A or NUFIP2 alleviates paclitaxel\u2010induced nociceptive hypersensitivity.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp291162","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:13:36Z","timestamp":1787220816000},"page":"7439-7463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["METTL3\u2010mediated m6A modification of\n                    <i>circMtmr7<\/i>\n                    contributes to paclitaxel\u2010induced peripheral neuropathy in the dorsal horn"],"prefix":"10.1113","volume":"604","author":[{"given":"Chaopeng","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoli","family":"He","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou China"},{"name":"Department of Anesthesiology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudena","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxiu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou China"},{"name":"Department of Physiology and Pain Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3992-9653","authenticated-orcid":false,"given":"Handong","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-8246","authenticated-orcid":false,"given":"Xiaohui","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114876"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-022-00534-0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15086"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/smsc.202400308"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11112"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.05.040"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-025-02925-1"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.2014.001776"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.02.004"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1513037"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01665"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01248-4"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01374-9"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.53227"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01399"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI174847"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114583"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113412"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1167"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.003"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204705"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-023-01449-7"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad371"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2021-328323"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104190"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.05.027"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.70034"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.09.020"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0666-1"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00300-w"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24951"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06287-w"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2022.0054"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01768-3"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117362"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-025-01206-5"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2021.11.005"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.04.018"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00653"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2017.31"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12049-0"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP291162","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP291162","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP291162","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:08:34Z","timestamp":1788275314000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP291162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":41,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1113\/JP291162"],"URL":"https:\/\/doi.org\/10.1113\/jp291162","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]},"assertion":[{"value":"2026-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}