Epigenetics in migraine: the Junior Editorial Board Members' vision.

backgroundMigraine represents the third leading cause of disability-adjusted life years among young females worldwide, responsible for physical and emotional distress along with reduced social functioning. The matter is further complicated by resistance and even refractoriness to the available treatments. Indeed, despite the several therapeutic strategies, remarkably improved by the development of the novel, specific drugs directed towards calcitonin-gene related peptide (CGRP) signalling, 40% patients, also undergoing anti-CGRP therapy, are still difficult-to-treat. The potential role of environmental factors and epigenetic modifications in the pathogenesis of migraine and in the responsiveness to treatments still remains poorly investigated. Moreover, the expression of a wide panel of serum microRNAs was recently related to frequency and features of migraine attacks. Thus, the aim of the present study is to analyze the possible epigenetic mechanisms at the root of differences in migraine features and response to treatments.

methodsEligibility criteria, search strategy and information sources are established a priori. PubMed, Scopus and Web of Science were inspected for studies published from database inception to the date of last search on October 2nd, 2025.

resultsA few studies so far support the role of DNA methylation in migraine chronification, indicating that these stable but reversible epigenetic modifications may influence the process of progression and transformation from episodic to chronic migraine. Altered DNA methylation sites were linked to genes involved in synaptic plasticity and estrogen receptor signaling. Up-regulation of circulating miRNAs was reduced following treatment with gepants. Within this complex figure, the role of the transient receptor potential (TRP) vanilloid 1 (TRPV1) in the trigeminal ganglia deserves deep investigation, including the prediction of response to first-line therapies such as triptans. Likewise, TRP ankyrin 1 (TRPA1) expression is subjected to pain-induced epigenetic modifications. DNA methylation and the modulation of histone deacetylase activity are implicated in the mechanisms of action of currently used preventative drugs, such as valproic acid and topiramate, and could serve as biomarkers of drug response. Finally, the role of miRNAs as potential biomarker for predicting the response to novel monoclonal antibodies, such as erenumab, has emerged in recent studies.

conclusionsThe role of epigenetic modifications of genes involved in the CGRP pathway, synaptic plasticity and TRPV1, TRPA1 and estrogen receptor signaling in migraine is emerging. Therefore, a deeper understanding of the impact of epigenetics in migraine pathophysiology and neuropharmacology is needed to revert chronification and personalize medicine in the field of migraine, improving efficacy and safety of treatments and widening the therapeutic armamentarium.