The vascular theory of migraine—a great story wrecked by the facts

The vascular theory of migraine—a great story wrecked by the facts

http://brain.oxfordjournals.org/cgi/content/long/132/1/6Peter J. GoadsbyDepartment of Neurology, University of California, San Francisco, CA, USA E-mail: peter.goadsby@ucsf.edu

Brain 2009 132(1):6-7; doi:10.1093/brain/awn321

Summary: If you trace history, migraine was theorized to be due to cranial vasodilatation by Willis (1664) and Wolf (1948). But later neuronal theories emerged (Liveing, 1873 and Gowers, 1888). Human experimental studies, observations on vascular change and therapeutics in the mid to late 20th century revived the vascular theory. But the same three key approaches, has put migraine back into the brain. Pituitary adenylate cyclase activating peptide (PACAP-38) produced cranial vasodilatation and triggered delayed migraine in sufferers (but not in controls or migraineurs infused with placebo) Vasoactive Intestinal Peptide (VIP) can induce an equal craniovascular vasodilatation, but doesn’t trigger migraine at all. So, it is not the dilation but receptor site activation that is important in migraine.So, vasodilatation is an epiphenomenon, neither necessary nor sufficient for the symptoms.The anti-migraine medication is shifting its target from vascular to neural action. This can free the patient from any potential vascular complication of anti-migraine therapeuticsTriptans, serotonin 5-HT 1B/1D receptor agonists are extremely effective treatments. They were initially developed as cranial vasoconstrictors. They are known to have effects on neuronal transmission in the brain.CGRP receptor antagonists (olcegepant, telcagepant)are also effective without vascular effects.Vasoconstriction is not required since dilation is not a key part of the process.In the new light, migraine becomes a disorder of the brain, with a new class of treatment available – CGRP receptor agonists (gepants)The author also feels that the demise of the vascular theory ushers in a new era for medicine development resulting in better management of migraine.

Also see the article:
PACAP38 induces migraine-like attacks in patients with migraine without aura (Henrik Winther Schytz, Steffen Birk, Troels Wienecke, Christina Kruuse, Jes Olesen and Messoud Ashina)

http://brain.oxfordjournals.org/cgi/content/long/132/1/16