Epigenetic DNA methylation changes in Chronic and Episodic migraine

Background: No valid biomarkers are available to detect among patients who suffer from Episodic (EM) and Chronic migraine (CM) those at greatest risk of develop a Medication Overuse Headache (MOH). Several evidences confirmed that pain vulnerability and attitude to chronic pain sensitivity are heritable via genetic but also epigenetic pathways though changes in DNA expression. Epigenetic mechanisms would have the potential to link early life events, neuro-inflammation and brain plasticity in the aetiology of migraine chronification. Method: The aim of this pilot study was to identify changes in DNA methylation associated with headache chronification comparing controls without headache (HC), episodic migraineurs and patients suffering from MOH. In all selected subjects, genome-wide DNA methylation levels were characterized longitudinally at baseline and during follow-up using the Infinium HumanMethylationEPIC Bead-Chip. Results: A total of 25 patients with MOH were enrolled at baseline (T0), of these 18 completed the 6 months follow up (T3). In the group of EM, 20 patients were enrolled and completed the 6-month follow up (T1). 13 HC subjects were enrolled at T0, and 11 completed study. Comparing MOH vs HC group at T0, none differentially methylated regions (DMRs) reached statistical significance. Nevertheless 29 DMRs had a delta of at least 0.05 in at least one CpG site. One of the most significant CpG site identified was at the chr10:76993892 island, which maps in the COMT (catechol-O-methyltransferase) gene and resulted hypermethylated in MOH. Discussion: These preliminary data suggest a role in MOH of epigenetic processes involved in aberrant immune-inflammatory responses and deregulation of dopaminergic neurotransmission theoretically implied in mechanisms of brain plasticity which control drug addiction and cognitive-emotional processes. However, all these data are preliminary and require replication and validation in a larger sample.