Migraine is a highly prevalent disabling disorder affecting approximately 1 billion people worldwide.1 Its pathophysiology involves activation and sensitisation of the trigeminovascular system, resulting in the release of neuropeptides, such as pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and calcitonin gene-related peptide (CGRP).2

Infusion of either peptide in human experimental models can trigger migraine-like attacks, providing the rationale for targeting these pathways therapeutically.3 4 Accordingly, highly effective anti-CGRP agents are now available for both acute and preventive migraine treatment,5 and an anti-PACAP-38 monoclonal antibody has recently shown efficacy in a phase 2 trial.6 Although plasma CGRP levels are elevated in patients with migraine compared with healthy controls (HCs), its clinical utility is limited by a short half-life and low circulating concentrations.7 8

Plasma PACAP-38 concentrations have been investigated with conflicting results: some studies reported higher ictal levels during…