Background and aim: A key element in the cluster headache (CH) attack is activation of the trigemino-autonomic reflex of which the vasoactive peptides calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) are known mediators. This evidence concerns the gene ADCYAP1 and Cluster headache.