CGRP as a neuropeptide in migraine: lessons from mice : CGRP as a neuropeptide in migraine

Scientific evidence supports the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation, and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals. Evidence of altered brain excitability emerged from clinical and preclinical investigation of sensory auras, ictal and interictal hypersensitivity to visual, auditory, and olfactory stimulation, and reduced activation of descending inhibitory pain pathways. Data supporting the activation and sensitization of the trigeminovascular system include the progressive development of cephalic and whole-body cutaneous allodynia during a migraine attack. In addition, structural and functional alterations include the presence of subcortical white mater lesions, thickening of cortical areas involved in processing sensory information, and cortical neuroplastic changes induced by cortical spreading depression. Here, we review recent anatomical data on the trigeminovascular pathway and its activation by cortical spreading depression, a novel understanding of the neural substrate of migraine-type photophobia, and modulation of the trigeminovascular pathway by the brainstem, hypothalamus and cortex. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Migraine is a collection of perplexing neurological conditions in which the brain and its associated tissues have been implicated as major players during an attack. Once considered exclusively a disorder of blood vessels, compelling evidence has led to the realization that migraine represents a highly choreographed interaction between major inputs from both the peripheral and central nervous systems, with the trigeminovascular system and the cerebral cortex among the main players. Advances in in vivo and in vitro technologies have informed us about the significance to migraine of events such as cortical spreading depression and activation of the trigeminovascular system and its constituent neuropeptides, as well as about the importance of neuronal and glial ion channels and transporters that contribute to the putative cortical excitatory/inhibitory imbalance that renders migraineurs susceptible to an attack. This review focuses on emerging concepts that drive the science of migraine in both a mechanistic direction and a therapeutic direction.