The first direct evidence that highlighted the potential significance of PACAP in the pathophysiology of migraine came from observations made in a human study [60] where intravenous administration of PACAP-38 caused headache and vasodilation in healthy subjects as well as in migraineurs, and lead to delayed-type migraine-like attacks exclusively in migraine patients without aura (65–75%), a feature remarkably similar to that previously reported after nitroglycerin infusion [61, 62]. Here, ADCYAP1 is linked to migraine disorder.