Induction of Migraine Attacks With Aura Using Pituitary Adenylate Cyclase Activating Polypeptide-38

Pituitary Adenylate Cyclase Activating Polypeptide-38 (PACAP-38) is a key neuropeptide in migraine pathophysiology and treatment. This study investigates whether PACAP-38 administration can trigger aura in individuals with a diagnosis of migraine with aura.

In a series of studies, pharmacological triggers of migraine headache were able to induce aura as well migraine headache. Recent open-label findings show that calcitonin gene-related peptide (CGRP) can trigger aura attacks-despite its limited ability to cross the blood-brain barrier. This suggests CGRP might induce migraine aura via trigeminovascular activation, the same pathway involved in migraine headache. To further explore this concept, it is fundamental to examine whether other migraine-inducing signaling molecules that pass the BBB to a minimal degree, such as PACAP-38, are able to induce aura as well. If PACAP-38 is able to induce aura, the anti-PACAP monoclonal antibody may provide a promising therapeutic option for preventing migraine with aura. To validate this effect, a randomized, double-blind, placebo-controlled trial is essential. Its outcomes could inform future therapies targeting the migraine-aura connection.