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A DNA methylation signature in the stress driver gene Fkbp5 indicates a neuropathic component in chronic pain

Maiarù, M. ORCID:, Acton, R. J., Woźniak, E. L., Mein, C. A., Bell, C. G. ORCID: and Géranton, S. M. ORCID: (2023) A DNA methylation signature in the stress driver gene Fkbp5 indicates a neuropathic component in chronic pain. Clinical Epigenetics, 15. 155. ISSN 1868-7083

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To link to this item DOI: 10.1186/s13148-023-01569-8


Background: Epigenetic changes can bring insight into gene regulatory mechanisms associated with disease pathogenicity, including chronicity and increased vulnerability. To date, we are yet to identify genes sensitive to epigenetic regulation that contribute to the maintenance of chronic pain and with an epigenetic landscape indicative of the susceptibility to persistent pain. Such genes would provide a novel opportunity for better pain management, as their epigenetic profile could be targeted for the treatment of chronic pain or used as an indication of vulnerability for prevention strategies. Here, we investigated the epigenetic profile of the gene Fkbp5 for this potential, using targeted bisulphite sequencing in rodent pre-clinical models of chronic and latent hypersensitive states. Results: The Fkbp5 promoter DNA methylation (DNAm) signature in the CNS was significantly different between models of persistent pain, and there was a significant correlation between CNS and peripheral blood Fkbp5 DNAm, indicating that further exploration of Fkbp5 promoter DNAm as an indicator of chronic pain pathogenic origin is warranted. We also found that maternal separation, which promotes the persistency of inflammatory pain in adulthood, was accompanied by long-lasting reduction in Fkbp5 DNAm, suggesting that Fkbp5 DNAm profile may indicate the increased vulnerability to chronic pain in individuals exposed to trauma in early life. Conclusions: Overall, our data demonstrate that the Fkbp5 promoter DNAm landscape brings novel insight into the differing pathogenic origins of chronic pain, may be able to stratify patients and predict the susceptibility to chronic pain.

Item Type:Article
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:113588
Uncontrolled Keywords:DNA methylation, Vulnerability, Chronic pain, Preclinical Models, Fkbp5, Humans, Tacrolimus Binding Proteins, Maternal Deprivation, DNA Methylation, Gene Expression Regulation, Epigenesis, Genetic, Chronic Pain


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