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Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2

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 understa...

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Autores principales: Oliveira, Ana MM, Litke, Christian, Paldy, Eszter, Hagenston, Anna M, Lu, Jianning, Kuner, Rohini, Bading, Hilmar, Mauceri, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362517/
https://www.ncbi.nlm.nih.gov/pubmed/30638145
http://dx.doi.org/10.1177/1744806919827469
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author Oliveira, Ana MM
Litke, Christian
Paldy, Eszter
Hagenston, Anna M
Lu, Jianning
Kuner, Rohini
Bading, Hilmar
Mauceri, Daniela
author_facet Oliveira, Ana MM
Litke, Christian
Paldy, Eszter
Hagenston, Anna M
Lu, Jianning
Kuner, Rohini
Bading, Hilmar
Mauceri, Daniela
author_sort Oliveira, Ana MM
collection PubMed
description 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’s 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’s 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.
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spelling pubmed-63625172019-02-15 Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2 Oliveira, Ana MM Litke, Christian Paldy, Eszter Hagenston, Anna M Lu, Jianning Kuner, Rohini Bading, Hilmar Mauceri, Daniela Mol Pain Research Article 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’s 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’s 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. SAGE Publications 2019-02-04 /pmc/articles/PMC6362517/ /pubmed/30638145 http://dx.doi.org/10.1177/1744806919827469 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) 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
Oliveira, Ana MM
Litke, Christian
Paldy, Eszter
Hagenston, Anna M
Lu, Jianning
Kuner, Rohini
Bading, Hilmar
Mauceri, Daniela
Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2
title Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2
title_full Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2
title_fullStr Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2
title_full_unstemmed Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2
title_short Epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo DNA methyltransferase Dnmt3a2
title_sort epigenetic control of hypersensitivity in chronic inflammatory pain by the de novo dna methyltransferase dnmt3a2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362517/
https://www.ncbi.nlm.nih.gov/pubmed/30638145
http://dx.doi.org/10.1177/1744806919827469
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