Role of PACAP in migraine headaches

Migraine is a complex disorder with a wide spectrum of clinical symptoms, and affects more than 16% of the general population. Despite its high heritability, the genetic basis of migraine remains unclear in most cases, and appropriate prophylactic and clinical therapy is not always available. Recent years have nevertheless seen considerable progress in understanding the cellular and circuit mechanisms of migraine (Vecsei et al. , 2013). In this issue of Brain , Faisal Amin and colleagues add to this progress by identifying the PAC1 receptor as a potentially important candidate therapeutic target (Amin et al. , 2014).Since the 1990s, a central theme of migraine research has been the trigeminovascular theory (Moskowitz, 1992). The trigeminovascular system provides an important pain-transmission link between the vascular (dural and cortical) and neuronal (brainstem and thalamus) regions. The sensory trigeminal unit is controlled by the descending pathways from the monoaminergic nuclei, and a number of neuropeptides, such as calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), have …