{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:18:28Z","timestamp":1790363908230,"version":"4.1.0"},"reference-count":42,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Emmy Noether OL 437\/1-1"],"award-info":[{"award-number":["Emmy Noether OL 437\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1158 projet A05"],"award-info":[{"award-number":["SFB1158 projet A05"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1158 projet A08"],"award-info":[{"award-number":["SFB1158 projet A08"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1158 projet B01"],"award-info":[{"award-number":["SFB1158 projet B01"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1158 projet B06"],"award-info":[{"award-number":["SFB1158 projet B06"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>Chronic pain is a pathological manifestation of neuronal plasticity supported by altered gene transcription in spinal cord neurons that results in long-lasting hypersensitivity. Recently, the concept that epigenetic regulators might be important in pathological pain has emerged, but a clear understanding of the molecular players involved in the process is still lacking. In this study, we linked Dnmt3a2, a synaptic activity-regulated de novo DNA methyltransferase, to chronic inflammatory pain. We observed that Dnmt3a2 levels are increased in the spinal cord of adult mice following plantar injection of Complete Freund\u2019s Adjuvant, an in vivo model of chronic inflammatory pain. In vivo knockdown of Dnmt3a2 expression in dorsal horn neurons blunted the induction of genes triggered by Complete Freund\u2019s Adjuvant injection. Among the genes whose transcription was found to be influenced by Dnmt3a2 expression in the spinal cord is Ptgs2, encoding for Cox-2, a prime mediator of pain processing. Lowering the levels of Dnmt3a2 prevented the establishment of long-lasting inflammatory hypersensitivity. These results identify Dnmt3a2 as an important epigenetic regulator needed for the establishment of central sensitization. Targeting expression or function of Dnmt3a2 may be suitable for the treatment of chronic pain.<\/jats:p>","DOI":"10.1177\/1744806919827469","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T01:11:28Z","timestamp":1547428288000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2"],"prefix":"10.1177","volume":"15","author":[{"given":"Ana MM","family":"Oliveira","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Interdisciplinary Centre for Neurosciences, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9403-4233","authenticated-orcid":false,"given":"Christian","family":"Litke","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Interdisciplinary Centre for Neurosciences, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Paldy","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M","family":"Hagenston","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Interdisciplinary Centre for Neurosciences, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianning","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohini","family":"Kuner","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilmar","family":"Bading","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Interdisciplinary Centre for Neurosciences, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1225-4633","authenticated-orcid":false,"given":"Daniela","family":"Mauceri","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Interdisciplinary Centre for Neurosciences, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"bibr1-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.162"},{"key":"bibr2-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5472.1765"},{"key":"bibr3-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.10.037"},{"key":"bibr4-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3531"},{"key":"bibr5-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000604"},{"key":"bibr6-1744806919827469","doi-asserted-by":"crossref","first-page":"6946","DOI":"10.1523\/JNEUROSCI.2345-16.2017","volume":"37","author":"Hemstedt TJ","year":"2017","journal-title":"J Neurosci"},{"key":"bibr7-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.04.022"},{"key":"bibr8-1744806919827469","doi-asserted-by":"crossref","first-page":"23039","DOI":"10.1074\/jbc.M115.654962","volume":"290","author":"Mauceri D","year":"2015","journal-title":". J Biol Chem"},{"key":"bibr9-1744806919827469","doi-asserted-by":"crossref","first-page":"8074","DOI":"10.1074\/jbc.M112.432773","volume":"288","author":"Schlumm F","year":"2013","journal-title":"J Biol Chem"},{"key":"bibr10-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3151"},{"key":"bibr11-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.12.008"},{"key":"bibr12-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205312200"},{"key":"bibr13-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.175"},{"key":"bibr14-1744806919827469","author":"Cannella N","journal-title":"."},{"key":"bibr15-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2013.06.008"},{"key":"bibr16-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.01.012"},{"key":"bibr17-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.08.040"},{"key":"bibr18-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1177\/1744806917740681"},{"key":"bibr19-1744806919827469","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.2147\/JPR.S130654","volume":"10","author":"Shao C","journal-title":"J Pain Res"},{"key":"bibr20-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14712"},{"key":"bibr21-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.025"},{"key":"bibr22-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1126\/science.1715095"},{"key":"bibr23-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/385260a0"},{"key":"bibr24-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.09.024"},{"key":"bibr25-1744806919827469","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41467-017-00341-w","volume":"8","author":"Paldy E","year":"2017","journal-title":"Nat Commun"},{"key":"bibr26-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/328632a0"},{"key":"bibr27-1744806919827469","first-page":"287","volume":"119","author":"Vardeh D","year":"2009","journal-title":"J Clin Invest"},{"key":"bibr28-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.42.092401.143905"},{"key":"bibr29-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-12-05031.2003"},{"key":"bibr30-1744806919827469","volume":"6","author":"Lu JN","year":"2015","journal-title":"Nature Commun"},{"key":"bibr31-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/nm1406"},{"key":"bibr32-1744806919827469","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00217"},{"key":"bibr33-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000894"},{"key":"bibr34-1744806919827469","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2018.00332","volume":"11","author":"Saunders J","year":"2018","journal-title":"Front Mol Neurosci"},{"key":"bibr35-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2341"},{"key":"bibr36-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1101\/lm.042739.116"},{"key":"bibr37-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2900"},{"key":"bibr38-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.09.003"},{"key":"bibr39-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2015.02.001"},{"key":"bibr40-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1186\/gm416"},{"key":"bibr41-1744806919827469","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.68"},{"key":"bibr42-1744806919827469","volume":"517","author":"Guo X","year":"2015","journal-title":"Nature"}],"container-title":["Molecular Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1744806919827469","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1744806919827469","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1744806919827469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:17:00Z","timestamp":1777709820000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1744806919827469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1]]},"references-count":42,"alternative-id":["10.1177\/1744806919827469"],"URL":"https:\/\/doi.org\/10.1177\/1744806919827469","relation":{},"ISSN":["1744-8069","1744-8069"],"issn-type":[{"value":"1744-8069","type":"print"},{"value":"1744-8069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1]]},"article-number":"1744806919827469"}}