{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T06:51:31Z","timestamp":1793170291861,"version":"4.5.0"},"reference-count":25,"publisher":"Society for Neuroscience","issue":"29","license":[{"start":{"date-parts":[[2015,1,16]],"date-time":"2015-01-16T00:00:00Z","timestamp":1421366400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"accepted":{"date-parts":[[2014,5,30]]},"published-print":{"date-parts":[[2014,7,16]]},"abstract":"<jats:p>Emerging evidence has shown that miRNA-mediated gene expression modulation contributes to chronic pain, but its functional regulatory mechanism remains unknown. Here, we found that complete Freund's adjuvant (CFA)-induced chronic inflammation pain significantly reduced miRNA-219 (miR-219) expression in mice spinal neurons. Furthermore, the expression of spinal CaMKII\u03b3, an experimentally validated target of miR-219, was increased in CFA mice. Overexpression of spinal miR-219 prevented and reversed thermal hyperalgesia and mechanical allodynia and spinal neuronal sensitization induced by CFA. Concurrently, increased expression of spinal CaMKII\u03b3 was reversed by miR-219 overexpression. Downregulation of spinal miR-219 in naive mice induced pain-responsive behaviors and increased p-NMDAR1 expression, which could be inhibited by knockdown of CaMKII\u03b3. Bisulfite sequencing showed that CFA induced the hypermethylation of CpG islands in the miR-219 promoter. Treatment with demethylation agent 5\u2032-aza-2\u2032-deoxycytidine markedly attenuated pain behavior and spinal neuronal sensitization, which was accompanied with the increase of spinal miR-219 and decrease of CaMKII\u03b3 expression. Together, we conclude that methylation-mediated epigenetic modification of spinal miR-219 expression regulates chronic inflammatory pain by targeting CaMKII\u03b3.<\/jats:p>","DOI":"10.1523\/jneurosci.5346-13.2014","type":"journal-article","created":{"date-parts":[[2014,7,16]],"date-time":"2014-07-16T16:34:41Z","timestamp":1405528481000},"page":"9476-9483","source":"Crossref","is-referenced-by-count":102,"title":["Epigenetic Modification of Spinal miR-219 Expression Regulates Chronic Inflammation Pain by Targeting 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