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An epigenetic hypothesis for the genomic memory of pain
Chronic pain is accompanied with long-term sensory, affective and cognitive disturbances. What are the mechanisms that mediate the long-term consequences of painful experiences and embed them in the genome? We hypothesize that alterations in DNA methylation, an enzymatic covalent modification of cyt...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371710/ https://www.ncbi.nlm.nih.gov/pubmed/25852480 http://dx.doi.org/10.3389/fncel.2015.00088 |
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author | Alvarado, Sebastian Tajerian, Maral Suderman, Matthew Machnes, Ziv Pierfelice, Stephanie Millecamps, Magali Stone, Laura S. Szyf, Moshe |
author_facet | Alvarado, Sebastian Tajerian, Maral Suderman, Matthew Machnes, Ziv Pierfelice, Stephanie Millecamps, Magali Stone, Laura S. Szyf, Moshe |
author_sort | Alvarado, Sebastian |
collection | PubMed |
description | Chronic pain is accompanied with long-term sensory, affective and cognitive disturbances. What are the mechanisms that mediate the long-term consequences of painful experiences and embed them in the genome? We hypothesize that alterations in DNA methylation, an enzymatic covalent modification of cytosine bases in DNA, serve as a “genomic” memory of pain in the adult cortex. DNA methylation is an epigenetic mechanism for long-term regulation of gene expression. Neuronal plasticity at the neuroanatomical, functional, morphological, physiological and molecular levels has been demonstrated throughout the neuroaxis in response to persistent pain, including in the adult prefrontal cortex (PFC). We have previously reported widespread changes in gene expression and DNA methylation in the PFC many months following peripheral nerve injury. In support of this hypothesis, we show here that up-regulation of a gene involved with synaptic function, Synaptotagmin II (syt2), in the PFC in a chronic pain model is associated with long-term changes in DNA methylation. The challenges of understanding the contributions of epigenetic mechanisms such as DNA methylation within the PFC to pain chronicity and their therapeutic implications are discussed. |
format | Online Article Text |
id | pubmed-4371710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-43717102015-04-07 An epigenetic hypothesis for the genomic memory of pain Alvarado, Sebastian Tajerian, Maral Suderman, Matthew Machnes, Ziv Pierfelice, Stephanie Millecamps, Magali Stone, Laura S. Szyf, Moshe Front Cell Neurosci Neuroscience Chronic pain is accompanied with long-term sensory, affective and cognitive disturbances. What are the mechanisms that mediate the long-term consequences of painful experiences and embed them in the genome? We hypothesize that alterations in DNA methylation, an enzymatic covalent modification of cytosine bases in DNA, serve as a “genomic” memory of pain in the adult cortex. DNA methylation is an epigenetic mechanism for long-term regulation of gene expression. Neuronal plasticity at the neuroanatomical, functional, morphological, physiological and molecular levels has been demonstrated throughout the neuroaxis in response to persistent pain, including in the adult prefrontal cortex (PFC). We have previously reported widespread changes in gene expression and DNA methylation in the PFC many months following peripheral nerve injury. In support of this hypothesis, we show here that up-regulation of a gene involved with synaptic function, Synaptotagmin II (syt2), in the PFC in a chronic pain model is associated with long-term changes in DNA methylation. The challenges of understanding the contributions of epigenetic mechanisms such as DNA methylation within the PFC to pain chronicity and their therapeutic implications are discussed. Frontiers Media S.A. 2015-03-24 /pmc/articles/PMC4371710/ /pubmed/25852480 http://dx.doi.org/10.3389/fncel.2015.00088 Text en Copyright © 2015 Alvarado, Tajerian, Suderman, Machnes, Pierfelice, Millecamps, Stone and Szyf. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Alvarado, Sebastian Tajerian, Maral Suderman, Matthew Machnes, Ziv Pierfelice, Stephanie Millecamps, Magali Stone, Laura S. Szyf, Moshe An epigenetic hypothesis for the genomic memory of pain |
title | An epigenetic hypothesis for the genomic memory of pain |
title_full | An epigenetic hypothesis for the genomic memory of pain |
title_fullStr | An epigenetic hypothesis for the genomic memory of pain |
title_full_unstemmed | An epigenetic hypothesis for the genomic memory of pain |
title_short | An epigenetic hypothesis for the genomic memory of pain |
title_sort | epigenetic hypothesis for the genomic memory of pain |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371710/ https://www.ncbi.nlm.nih.gov/pubmed/25852480 http://dx.doi.org/10.3389/fncel.2015.00088 |
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