EPIGENETICS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) GENE FOR PAIN IN CHRONIC FATIGUE SYNDROME: AN EXPLORATIVE STUDY

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Polli A.1,2, Ickmans K.1,2, Ghosh M.3, Godderis L.3, Nijs J.4
1Pain in Motion International Research Group, Bruxelles, Belgium, 2Vrije Universiteit Brussel, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Bruxelles, Belgium, 3KU Leuven, Environment and Health, Leuven, Belgium, 4Vrije Universiteit Brussel, Pain in Motion (PiM) Research Group - Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy, Bruxelles, Belgium

Background: Pain is often referred as the most disabling symptom in patients with CFS. Previous knowledge showed that pain inhibitory mechanisms are impaired, complying with a picture of hypersensitivity of the central nervous system. Unravel the mechanisms of the aforementioned hypersensitivity of the central nervous system pain in patients with CFS is warranted. One of the crucial player for central sensitization is Brain-derived Neurotrophic Factor (BDNF). BDNF is a protein produced by a variety of cells, including neurons and immune cells. BDNF increases the sensitivity of the pain pathways in the CNS.
Epigenetics refers to alterations in gene expression, without changes in the underlying gene sequence. Epigenetic changes allow cells to respond to external factors. Accumulating evidence demonstrated that epigenetic modification of the expression of specific genes contributed to the pathogenesis of various disorders. This has led to breakthrough research findings and subsequent innovative treatments (e.g. new treatments for leukaemia). Understanding pain in CFS from an epigenetics viewpoint would provide a new paradigm for developing new strategies for pain treatment.

Purpose: It is hypothesized that differences in methylation patterns of the BDNF gene could play a more prevalent role in patients with CFS than in healthy controls and that epigenetic modifications would be stable in the short term period.

Methods: A cross-sectional design is set. Twenty patients with clear diagnonsis of CFS reporting persistent pain from more than 6 months, and twenty healthy controls will be recruited. Only women, between 18 and 65 years old, will be included in the study. HCs will be matched to patients´ characteristics (age, sex, BMI, levels of physical activity). Subjects undergo a comprehensive assessment, that includes blood withdrawal for the analysis of methylation in the BDNF gene, measures of cold and heat and pain thresholds using the TSA-II device (Medoc), and symptom reports assessing general health, level of physical activity, anxiety, pain, central sensitization and pain catastrophizing. To assess temporal stability of epigenetic modifications, subjects will undergo the same assessment twice within one week. Between the two assessments, subjects will wear an accelerometer, so that we have an objective measure of subjects’ physical activity. Parametric or robust statistics will be performed, according to the results from descriptive statistics. Between-subject analysis will serve to compare clinical characteristic, pain thresholds and pattern of BDNF methylation between patients and HCs. Within-subject analysis will look at temporal stability of measures in both CFS patients and controls.

Results: Data collection is nearly completed. Analysis is performed in January 2017, results will be ready by march 2017 the latest.

Conclusion(s): This is a pilot study on the role of Epigenetcs for Pain in CFS patients. Assessment is comprehensive, including clinical, neurophysiological and biological analysis. We believe this study would be a base for further research in the field of epigenetic and chronic pain.

Implications: In CFS, the field of Epigenetics is in its infancy. Our study will be the first targeting epigenetic mechanisms for pain in CFS patients and other chronic pain conditions.

Funding acknowledgements: This study was funded by the ME Research UK Association.

Topic: Pain & pain management

Ethics approval: The study was approved by the Ethical Committee of the Vrije Universiteit Brussel, Belgium.


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