{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:22:03Z","timestamp":1791350523193,"version":"4.3.1"},"reference-count":68,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T00:00:00Z","timestamp":1668297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MCIN\/AEI\/10.13039\/501100011033 and by \u201cERDF A way of making Europe\u201d;","award":["SAF2016-77732-R"],"award-info":[{"award-number":["SAF2016-77732-R"]}]},{"name":"MCIN\/AEI\/10.13039\/501100011033 and by \u201cERDF A way of making Europe\u201d;","award":["PID2019-104398RB-I00"],"award-info":[{"award-number":["PID2019-104398RB-I00"]}]},{"name":"MCIN\/AEI\/10.13039\/501100011033 and by \u201cERDF A way of making Europe\u201d;","award":["NVAL17\/23"],"award-info":[{"award-number":["NVAL17\/23"]}]},{"name":"MCIN\/AEI\/10.13039\/501100011033","award":["SAF2016-77732-R"],"award-info":[{"award-number":["SAF2016-77732-R"]}]},{"name":"MCIN\/AEI\/10.13039\/501100011033","award":["PID2019-104398RB-I00"],"award-info":[{"award-number":["PID2019-104398RB-I00"]}]},{"name":"MCIN\/AEI\/10.13039\/501100011033","award":["NVAL17\/23"],"award-info":[{"award-number":["NVAL17\/23"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Marqu\u00e9s de Valdecilla (IDIVAL)","award":["SAF2016-77732-R"],"award-info":[{"award-number":["SAF2016-77732-R"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Marqu\u00e9s de Valdecilla (IDIVAL)","award":["PID2019-104398RB-I00"],"award-info":[{"award-number":["PID2019-104398RB-I00"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Marqu\u00e9s de Valdecilla (IDIVAL)","award":["NVAL17\/23"],"award-info":[{"award-number":["NVAL17\/23"]}]},{"name":"Foundation Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","award":["SAF2016-77732-R"],"award-info":[{"award-number":["SAF2016-77732-R"]}]},{"name":"Foundation Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","award":["PID2019-104398RB-I00"],"award-info":[{"award-number":["PID2019-104398RB-I00"]}]},{"name":"Foundation Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","award":["NVAL17\/23"],"award-info":[{"award-number":["NVAL17\/23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuropathic pain is a prevalent and severe chronic syndrome, often refractory to treatment, whose development and maintenance may involve epigenetic mechanisms. We previously demonstrated a causal relationship between miR-30c-5p upregulation in nociception-related neural structures and neuropathic pain in rats subjected to sciatic nerve injury. Furthermore, a short course of an miR-30c-5p inhibitor administered into the cisterna magna exerts long-lasting antiallodynic effects via a TGF-\u03b21-mediated mechanism. Herein, we show that miR-30c-5p inhibition leads to global DNA hyper-methylation of neurons in the lumbar dorsal root ganglia and spinal dorsal horn in rats subjected to sciatic nerve injury. Specifically, the inhibition of miR-30-5p significantly increased the expression of the novo DNA methyltransferases DNMT3a and DNMT3b in those structures. Furthermore, we identified the mechanism and found that miR-30c-5p targets the mRNAs of DNMT3a and DNMT3b. Quantitative methylation analysis revealed that the promoter region of the antiallodynic cytokine TGF-\u03b21 was hypomethylated in the spinal dorsal horn of nerve-injured rats treated with the miR-30c-5p inhibitor, while the promoter of Nfyc, the host gene of miR-30c-5p, was hypermethylated. These results are consistent with long-term protection against neuropathic pain development after nerve injury. Altogether, our results highlight the key role of miR-30c-5p in the epigenetic mechanisms\u2019 underlying neuropathic pain and provide the basis for miR-30c-5p as a therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms232213994","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T02:29:32Z","timestamp":1668392972000},"page":"13994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Identification of Epigenetic Interactions between MicroRNA-30c-5p and DNA Methyltransferases in Neuropathic Pain"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-4852","authenticated-orcid":false,"given":"Raquel","family":"Franc\u00e9s","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Mata-Garrido","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain"},{"name":"Departamento de Anatom\u00eda y Biolog\u00eda Celular, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Servicio de Anestesiolog\u00eda, Hospital Universitario Marqu\u00e9s de Valdecilla, 39008 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Carcel\u00e9n","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3402-1152","authenticated-orcid":false,"given":"Miguel","family":"Lafarga","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain"},{"name":"Departamento de Anatom\u00eda y Biolog\u00eda Celular, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8225-6995","authenticated-orcid":false,"given":"Mar\u00eda Teresa","family":"Berciano","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain"},{"name":"Departamento de Biolog\u00eda Molecular, Universidad de Cantabria, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7710-1358","authenticated-orcid":false,"given":"Mar\u00eda A.","family":"Hurl\u00e9","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2447-8928","authenticated-orcid":false,"given":"M\u00f3nica","family":"Tramullas","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Valdecilla (IDIVAL), 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrn.2016.162","article-title":"Structural plasticity and reorganisation in chronic pain","volume":"18","author":"Kuner","year":"2017","journal-title":"Nat. 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