The methyl donor S-adenosyl methionine reverses the DNA methylation signature of chronic neuropathic pain in mouse frontal cortex
Introduction:. Chronic pain is associated with persistent but reversible structural and functional changes in the prefrontal cortex (PFC). This stable yet malleable plasticity implicates epigenetic mechanisms, including DNA methylation, as a potential mediator of chronic pain–induced cortical pathol...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2021-08-01
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| Series: | PAIN Reports |
| Online Access: | http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000000944 |
| _version_ | 1818671576269193216 |
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| author | Lucas Topham Stephanie Gregoire HyungMo Kang Mali Salmon-Divon Elad Lax Magali Millecamps Moshe Szyf Laura Stone |
| author_facet | Lucas Topham Stephanie Gregoire HyungMo Kang Mali Salmon-Divon Elad Lax Magali Millecamps Moshe Szyf Laura Stone |
| author_sort | Lucas Topham |
| collection | DOAJ |
| description | Introduction:. Chronic pain is associated with persistent but reversible structural and functional changes in the prefrontal cortex (PFC). This stable yet malleable plasticity implicates epigenetic mechanisms, including DNA methylation, as a potential mediator of chronic pain–induced cortical pathology. We previously demonstrated that chronic oral administration of the methyl donor S-adenosyl methionine (SAM) attenuates long-term peripheral neuropathic pain and alters global frontal cortical DNA methylation. However, the specific genes and pathways associated with the resolution of chronic pain by SAM remain unexplored.
Objective:. To determine the effect of long-term therapeutic exposure to SAM on the DNA methylation of individual genes and pathways in a mouse neuropathic pain model.
Methods:. Male CD-1 mice received spared nerve injury or sham surgery. Three months after injury, animals received SAM (20 mg/kg, oral, 3× a week) or vehicle for 16 weeks followed by epigenome-wide analysis of frontal cortex.
Results:. Peripheral neuropathic pain was associated with 4000 differentially methylated genomic regions that were enriched in intracellular signaling, cell motility and migration, cytoskeletal structure, and cell adhesion pathways. A third of these differentially methylated regions were reversed by SAM treatment (1415 regions representing 1013 genes). More than 100 genes with known pain-related function were differentially methylated after nerve injury; 29 of these were reversed by SAM treatment including Scn10a, Trpa1, Ntrk1, and Gfap.
Conclusion:. These results suggest a role for the epigenome in the maintenance of chronic pain and advance epigenetic modulators such as SAM as a novel approach to treat chronic pain. |
| first_indexed | 2024-12-17T07:26:12Z |
| format | Article |
| id | doaj.art-dfd6c4579eac464fa9757f78618a80ad |
| institution | Directory Open Access Journal |
| issn | 2471-2531 |
| language | English |
| last_indexed | 2024-12-17T07:26:12Z |
| publishDate | 2021-08-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | PAIN Reports |
| spelling | doaj.art-dfd6c4579eac464fa9757f78618a80ad2022-12-21T21:58:37ZengWolters KluwerPAIN Reports2471-25312021-08-0162e94410.1097/PR9.0000000000000944202107000-00015The methyl donor S-adenosyl methionine reverses the DNA methylation signature of chronic neuropathic pain in mouse frontal cortexLucas Topham0Stephanie Gregoire1HyungMo Kang2Mali Salmon-Divon3Elad Lax4Magali Millecamps5Moshe Szyf6Laura Stone7a Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canadaa Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canadaa Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canadac Department of Molecular Biology, Ariel University, Ariel, Israelc Department of Molecular Biology, Ariel University, Ariel, Israela Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canadad Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canadaa Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, CanadaIntroduction:. Chronic pain is associated with persistent but reversible structural and functional changes in the prefrontal cortex (PFC). This stable yet malleable plasticity implicates epigenetic mechanisms, including DNA methylation, as a potential mediator of chronic pain–induced cortical pathology. We previously demonstrated that chronic oral administration of the methyl donor S-adenosyl methionine (SAM) attenuates long-term peripheral neuropathic pain and alters global frontal cortical DNA methylation. However, the specific genes and pathways associated with the resolution of chronic pain by SAM remain unexplored. Objective:. To determine the effect of long-term therapeutic exposure to SAM on the DNA methylation of individual genes and pathways in a mouse neuropathic pain model. Methods:. Male CD-1 mice received spared nerve injury or sham surgery. Three months after injury, animals received SAM (20 mg/kg, oral, 3× a week) or vehicle for 16 weeks followed by epigenome-wide analysis of frontal cortex. Results:. Peripheral neuropathic pain was associated with 4000 differentially methylated genomic regions that were enriched in intracellular signaling, cell motility and migration, cytoskeletal structure, and cell adhesion pathways. A third of these differentially methylated regions were reversed by SAM treatment (1415 regions representing 1013 genes). More than 100 genes with known pain-related function were differentially methylated after nerve injury; 29 of these were reversed by SAM treatment including Scn10a, Trpa1, Ntrk1, and Gfap. Conclusion:. These results suggest a role for the epigenome in the maintenance of chronic pain and advance epigenetic modulators such as SAM as a novel approach to treat chronic pain.http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000000944 |
| spellingShingle | Lucas Topham Stephanie Gregoire HyungMo Kang Mali Salmon-Divon Elad Lax Magali Millecamps Moshe Szyf Laura Stone The methyl donor S-adenosyl methionine reverses the DNA methylation signature of chronic neuropathic pain in mouse frontal cortex PAIN Reports |
| title | The methyl donor S-adenosyl methionine reverses the DNA methylation signature of chronic neuropathic pain in mouse frontal cortex |
| title_full | The methyl donor S-adenosyl methionine reverses the DNA methylation signature of chronic neuropathic pain in mouse frontal cortex |
| title_fullStr | The methyl donor S-adenosyl methionine reverses the DNA methylation signature of chronic neuropathic pain in mouse frontal cortex |
| title_full_unstemmed | The methyl donor S-adenosyl methionine reverses the DNA methylation signature of chronic neuropathic pain in mouse frontal cortex |
| title_short | The methyl donor S-adenosyl methionine reverses the DNA methylation signature of chronic neuropathic pain in mouse frontal cortex |
| title_sort | methyl donor s adenosyl methionine reverses the dna methylation signature of chronic neuropathic pain in mouse frontal cortex |
| url | http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000000944 |
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