Altogether these data, along with the failure of a monoclonal antibody targeting the PAC1 receptor (AMG 301) in migraine prevention, raise some questions about the role of PAC1 receptor in the ignition of migraine-like attacks after both PACAP38 and VIP intravenous infusion, strongly suggesting the momentous role of VPAC1 and VPAC2 receptors as possible targets. Here, VIP is linked to migraine disorder.