{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:05:41Z","timestamp":1791270341453,"version":"4.1.0"},"reference-count":58,"publisher":"Society for Neuroscience","issue":"13","license":[{"start":{"date-parts":[[2010,9,30]],"date-time":"2010-09-30T00:00:00Z","timestamp":1285804800000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2010,3,31]]},"abstract":"<jats:p>\n                    Peripheral nerve injury causes neuropathic pain, which is characterized by the paradoxical sensations of positive and negative symptoms. Clinically, negative signs are frequently observed; however, their underlying molecular mechanisms are largely unknown. Dysfunction of C-fibers is assumed to underlie negative symptoms and is accompanied by long-lasting downregulation of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 sodium channel and \u03bc-opioid receptor (MOP) in the dorsal root ganglion (DRG). In the present study, we found that nerve injury upregulates neuron-restrictive silencer factor (NRSF) expression in the DRG neurons mediated through epigenetic mechanisms. In addition, chromatin immunoprecipitation analysis revealed that nerve injury promotes NRSF binding to the neuron-restrictive silencer element within MOP and Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 genes, thereby causing epigenetic silencing. Furthermore, NRSF knockdown significantly blocked nerve injury-induced downregulations of MOP and Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 gene expressions, C-fiber hypoesthesia, and the losses of peripheral morphine analgesia and Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8-selective blocker-induced hypoesthesia. Together, these data suggest that NRSF causes pathological and pharmacological dysfunction of C-fibers, which underlies the negative symptoms in neuropathic pain.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.5541-09.2010","type":"journal-article","created":{"date-parts":[[2010,3,31]],"date-time":"2010-03-31T13:00:19Z","timestamp":1270040419000},"page":"4806-4814","source":"Crossref","is-referenced-by-count":179,"title":["Epigenetic Gene Silencing Underlies C-Fiber Dysfunctions in Neuropathic Pain"],"prefix":"10.1523","volume":"30","author":[{"given":"Hitoshi","family":"Uchida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2010,3,31]]},"reference":[{"key":"2023041303432649000_30.13.4806.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2007.12.002"},{"key":"2023041303432649000_30.13.4806.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1156916"},{"key":"2023041303432649000_30.13.4806.3","doi-asserted-by":"publisher","DOI":"10.1038\/9195"},{"key":"2023041303432649000_30.13.4806.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2005.08.015"},{"key":"2023041303432649000_30.13.4806.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.03.013"},{"key":"2023041303432649000_30.13.4806.6","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneuro0113"},{"key":"2023041303432649000_30.13.4806.7","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5073fje"},{"key":"2023041303432649000_30.13.4806.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.10.012"},{"key":"2023041303432649000_30.13.4806.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401827101"},{"key":"2023041303432649000_30.13.4806.10","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1523\/JNEUROSCI.23-06-02112.2003","article-title":"Ischemic insults derepress the gene silencer REST in neurons destined to die","volume":"23","author":"Calderone","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303432649000_30.13.4806.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007383"},{"key":"2023041303432649000_30.13.4806.12","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181bef710"},{"key":"2023041303432649000_30.13.4806.13","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90298-8"},{"key":"2023041303432649000_30.13.4806.14","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135531"},{"key":"2023041303432649000_30.13.4806.15","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn093"},{"key":"2023041303432649000_30.13.4806.16","doi-asserted-by":"crossref","unstructured":"Devor M (2006) in Wall and Melzack's textbook of pain, Response of nerves to injury in relation to neuropathic pain, eds McMahon SB Koltzenburg M (Churchill Livingstone, Oxford), pp 905\u2013927.","DOI":"10.1016\/B0-443-07287-6\/50063-1"},{"key":"2023041303432649000_30.13.4806.17","doi-asserted-by":"crossref","unstructured":"Dickenson A Kieffer B (2006) in Wall and Melzack's textbook of pain, Opiates: basic mechanisms, eds McMahon SB Koltzenburg M (Churchill Livingstone, Oxford), pp 427\u2013442.","DOI":"10.1016\/B0-443-07287-6\/50032-1"},{"key":"2023041303432649000_30.13.4806.18","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1998.0204"},{"key":"2023041303432649000_30.13.4806.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611704104"},{"key":"2023041303432649000_30.13.4806.20","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90026-7"},{"key":"2023041303432649000_30.13.4806.21","doi-asserted-by":"crossref","unstructured":"H\u00f6kfelt T Zhang X Xu XJ Wiesenfeld-Hallin Z (2006) in Wall and Melzack's textbook of pain, Central consequences of peripheral nerve damage, eds McMahon SB Koltzenburg M (Churchill Livingstone, Oxford), pp 947\u2013959.","DOI":"10.1016\/B0-443-07287-6\/50065-5"},{"key":"2023041303432649000_30.13.4806.22","doi-asserted-by":"publisher","DOI":"10.1038\/nm1060"},{"key":"2023041303432649000_30.13.4806.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611364104"},{"key":"2023041303432649000_30.13.4806.24","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2000.0360"},{"key":"2023041303432649000_30.13.4806.25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.28.16483"},{"key":"2023041303432649000_30.13.4806.26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403633200"},{"key":"2023041303432649000_30.13.4806.27","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10768"},{"key":"2023041303432649000_30.13.4806.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050578797"},{"key":"2023041303432649000_30.13.4806.29","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-1-13"},{"key":"2023041303432649000_30.13.4806.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.05.035"},{"key":"2023041303432649000_30.13.4806.31","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90218-3"},{"key":"2023041303432649000_30.13.4806.32","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.22.12508-12518.2004"},{"key":"2023041303432649000_30.13.4806.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2007.08.009"},{"key":"2023041303432649000_30.13.4806.34","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.bbadis.2007.01.008","article-title":"TRP channels: targets for the relief of pain","volume":"1772","author":"Levine","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"2023041303432649000_30.13.4806.35","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(98)00045-1"},{"key":"2023041303432649000_30.13.4806.36","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.103614"},{"key":"2023041303432649000_30.13.4806.37","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-4-25"},{"key":"2023041303432649000_30.13.4806.38","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90219-4"},{"key":"2023041303432649000_30.13.4806.39","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(01)00286-X"},{"key":"2023041303432649000_30.13.4806.40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0091-07.2007"},{"key":"2023041303432649000_30.13.4806.41","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1523\/JNEUROSCI.18-04-01280.1998","article-title":"Neuronal expression of zinc finger transcription factor REST\/NRSF\/XBR gene","volume":"18","author":"Palm","year":"1998","journal-title":"J Neurosci"},{"key":"2023041303432649000_30.13.4806.42","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.010751"},{"key":"2023041303432649000_30.13.4806.43","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.046250"},{"key":"2023041303432649000_30.13.4806.44","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.060582"},{"key":"2023041303432649000_30.13.4806.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.01.005"},{"key":"2023041303432649000_30.13.4806.46","first-page":"219","article-title":"Neurological disease: listening to gene silencers","volume":"1","author":"Roopra","year":"2001","journal-title":"Mol Interv"},{"key":"2023041303432649000_30.13.4806.47","doi-asserted-by":"publisher","DOI":"10.1126\/science.7871435"},{"key":"2023041303432649000_30.13.4806.48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9881"},{"key":"2023041303432649000_30.13.4806.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.04.013"},{"key":"2023041303432649000_30.13.4806.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.08.041"},{"key":"2023041303432649000_30.13.4806.51","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-001-0083-1"},{"key":"2023041303432649000_30.13.4806.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.12.021"},{"key":"2023041303432649000_30.13.4806.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.06.003"},{"key":"2023041303432649000_30.13.4806.54","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-4-11"},{"key":"2023041303432649000_30.13.4806.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.7635"},{"key":"2023041303432649000_30.13.4806.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.04.017"},{"key":"2023041303432649000_30.13.4806.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.11.025"},{"key":"2023041303432649000_30.13.4806.58","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(83)90201-4"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.5541-09.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T15:51:42Z","timestamp":1681401102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.5541-09.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,31]]},"references-count":58,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2010,3,31]]},"published-print":{"date-parts":[[2010,3,31]]}},"alternative-id":["10.1523\/JNEUROSCI.5541-09.2010"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.5541-09.2010","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.2953960.2624060","asserted-by":"object"}]},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,31]]}}}