ADCYAP1R1 and Headache: Abnormal activation and sensitization of the central trigeminovascular pain pathway mediate migraine and the release of these peptides.5 Intravenous infusion of PACAP38 but not VIP induces delayed migraine-like headaches, indicating that PAC1R is playing a major role in migraine6 and suggesting PACAP38-PAC1R as a potential therapeutic target for migraine treatment.7