Much is still to be discovered regarding the mechanisms of CGRP action and the prevention of its signalling on trigeminal afferents, which causes sensitization in both migraine-related preclinical studies [14,23,24,25,26,27] and in patients suffering from primary headaches, triggering their specific types of headaches [9,28,29,30,31]. The gene discussed is CALCA; the disease is Headache.