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G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury
Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction o...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153028/ https://www.ncbi.nlm.nih.gov/pubmed/27927796 http://dx.doi.org/10.1177/1744806916682242 |
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author | Liang, Lingli Zhao, Jian-Yuan Gu, Xiyao Wu, Shaogen Mo, Kai Xiong, Ming Marie Lutz, Brianna Bekker, Alex Tao, Yuan-Xiang |
author_facet | Liang, Lingli Zhao, Jian-Yuan Gu, Xiyao Wu, Shaogen Mo, Kai Xiong, Ming Marie Lutz, Brianna Bekker, Alex Tao, Yuan-Xiang |
author_sort | Liang, Lingli |
collection | PubMed |
description | Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia. Blocking these increases rescued dorsal root ganglia Oprm1, Oprk1, and Oprd1 gene expression and morphine or loperamide analgesia and prevented the development of morphine or loperamide-induced analgesic tolerance under neuropathic pain conditions. Conversely, mimicking these increases reduced the expression of three opioid receptors and promoted the mu opioid receptor-gated release of primary afferent neurotransmitters. Mechanistically, nerve injury-induced increases in the binding activity of G9a and H3K9me2 to the Oprm1 gene were associated with the reduced binding of cyclic AMP response element binding protein to the Oprm1 gene. These findings suggest that G9a participates in the nerve injury-induced reduction of the Oprm1 gene likely through G9a-triggered blockage in the access of cyclic AMP response element binding protein to this gene. |
format | Online Article Text |
id | pubmed-5153028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-51530282016-12-19 G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury Liang, Lingli Zhao, Jian-Yuan Gu, Xiyao Wu, Shaogen Mo, Kai Xiong, Ming Marie Lutz, Brianna Bekker, Alex Tao, Yuan-Xiang Mol Pain Research Article Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia. Blocking these increases rescued dorsal root ganglia Oprm1, Oprk1, and Oprd1 gene expression and morphine or loperamide analgesia and prevented the development of morphine or loperamide-induced analgesic tolerance under neuropathic pain conditions. Conversely, mimicking these increases reduced the expression of three opioid receptors and promoted the mu opioid receptor-gated release of primary afferent neurotransmitters. Mechanistically, nerve injury-induced increases in the binding activity of G9a and H3K9me2 to the Oprm1 gene were associated with the reduced binding of cyclic AMP response element binding protein to the Oprm1 gene. These findings suggest that G9a participates in the nerve injury-induced reduction of the Oprm1 gene likely through G9a-triggered blockage in the access of cyclic AMP response element binding protein to this gene. SAGE Publications 2016-12-07 /pmc/articles/PMC5153028/ /pubmed/27927796 http://dx.doi.org/10.1177/1744806916682242 Text en © The Author(s) 2016 http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Research Article Liang, Lingli Zhao, Jian-Yuan Gu, Xiyao Wu, Shaogen Mo, Kai Xiong, Ming Marie Lutz, Brianna Bekker, Alex Tao, Yuan-Xiang G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury |
title | G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury |
title_full | G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury |
title_fullStr | G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury |
title_full_unstemmed | G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury |
title_short | G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury |
title_sort | g9a inhibits creb-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153028/ https://www.ncbi.nlm.nih.gov/pubmed/27927796 http://dx.doi.org/10.1177/1744806916682242 |
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