We focussed on the CGRP-ergic system because of its prominent role in migraine [23] We investigated DNA methylation in the Calcitonin related peptide alpha (Calca), receptor activity-modifying protein 1 (Ramp1), calcitonin receptor component protein (Crcp), calcitonin receptor-like receptor (Calcrl), upstream stimulating factor 2 (Usf2), Estrogen receptor 1 (Esr1), G-protein coupled estrogen receptor 1 (Gper), nitric oxide synthase 3 (Nos3)) and Mthfr genes in several tissues relevant to the pathophysiology of migraine (dura mater, trigeminal ganglion and trigeminal caudal nucleus). This evidence concerns the gene NOS3 and migraine disorder.