Clinical studies have shown that CGRP levels are heightened both during and between migraine attacks (Goadsby et al., 1990, Ashina et al., 2000, Russo, 2019), that peripheral infusion of CGRP prompts the onset of migraine-like headaches in ∼ 66% of migraine patients (Russo, 2019, Ashina et al., 2019), and that CGRP-based drugs that are believed to primarily act in the periphery (Johnson, 2019) are effective in about 50% of patients (Edvinsson et al., 2018, Rapoport and McAllister, 2020). This evidence concerns the gene CALCA and migraine disorder.