Like CGRP, PACAP’s peripheral mechanisms include being a vasodilatory peptide that is elevated in migraine and causal in stimulating migraine responses in both humans and rodents; both preclinical and clinical trials suggest likelihood of future therapeutic success in migraine and especially for some of the more complex feature of migraine, including chronic and medication overuse headache [83–85]. This evidence concerns the gene ADCYAP1 and migraine disorder.