Wyns et al. (2026)
- Authors: Arne Wyns, Jolien Hendrix, Jente Van Campenhout, Yanthe Buntinx, Huan-Yu Xiong, Elke De Bruyne, Lode Godderis, Jo Nijs, David Rice, Daniel Chiang, Andrea Polli
- Institutes: Pain in Motion (PiM) International Research Group, Vrije Universiteit Brussel, Belgium, Department of Public Health and Primary Care, KU Leuven, Belgium, Flanders Research Foundation—FWO, Brussels, Belgium, Translational Oncology Research Center (TORC), Vrije Universiteit Brussel, Belgium
- Publisher: International Journal of Molecular Sciences (MDPI)
- Link: DOI
Summary
This study is the first to identify specific epigenetic changes in the mu-opioid receptor 1 gene (OPRM1) in patients with ME/CFS and Fibromyalgia. The discovery of hypermethylation suggests that the body’s natural pain-relief system may be biologically ‘silenced’ at the genetic level, contributing to chronic pain and fatigue. These findings provide a new potential biomarker and a target for future treatments aimed at restoring normal opioid receptor function.
What was researched?
The researchers investigated whether epigenetic modifications, specifically the methylation of the OPRM1 💊 gene promoter, contribute to the dysfunction of the endogenous opioid system in patients with ME/CFS and Fibromyalgia.
Why was it researched?
The study aimed to understand the biological mechanisms behind chronic pain and fatigue, focusing on the hypothesis that the opioid system—responsible for natural pain modulation—is deregulated in these conditions.
How was it researched?
In a repeated-measures design, 28 female patients and 26 healthy controls underwent blood sampling, clinical questionnaires, and quantitative sensory testing (QST) twice within four days. DNA methylation was analyzed using liquid chromatography–tandem mass spectrometry and targeted pyrosequencing of the OPRM1, COMT, and BDNF gene regions.
What has been found?
Patients showed significantly higher OPRM1 promoter methylation compared to controls, a state often linked to gene silencing. This hypermethylation was independent of symptom severity or pain sensitivity scores. Additionally, OPRM1 methylation strongly correlated with the methylation patterns of the BDNF gene, which is involved in central sensitization.
Discussion
A key strength was the use of a repeated-measures design to ensure findings were stable over time. However, the study was limited by the lack of direct measurement of OPRM1 protein levels and the use of peripheral blood cells as a proxy for central nervous system activity.
Conclusion & Future Work
The findings support the hypothesis of a dysregulated opioidergic system in ME/CFS and FM driven by epigenetic silencing. Future research should include functional assays to confirm if these genetic changes directly lead to reduced opioid receptor availability in the brain.