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. This evidence concerns the gene VIPR2 and migraine disorder.