There is no solid evidence yet of PACAP38 passing the BBB following exogenous infusion in migraine models that can lead to brain function and brain vessel changes, so it is possible that the PACAP migraine inducing effect is caused by peripheral mechanisms, which could be via inducing changes in the meninges or affecting nociceptors in extracranial vessels both devoid of the BBB. This evidence concerns the gene ADCYAP1 and migraine disorder.