From migraine mechanisms to innovative therapeutic drugs

Abstract

Over the past 15 years there has been enormous scientific and clinical progress in the field of headache. New and more effective treatments have emerged as migraine science has been translated into clinical practice. Despite the progress, not all patients respond to available treatments, and individual patients respond differentially for different attacks. Improving the outcomes of migraine patients requires further progress in using available knowledge to develop new treatments and novel combinations of existing treatments. The scientific foundation and opportunity for the future of acute migraine therapy provide the basis of this supplement. Migraine is a primary episodic headache disorder characterized by a cascade of events that involve various combinations of neurologic, gastrointestinal, and autonomic changes. Headache is probably caused by activation of meningeal and blood vessel nociceptors combined with an alteration in central pain modulation. Headache and its associated neurovascular changes are subserved by the trigeminal system. A link also exists between the migraine aura and headache. Cortical spreading depression (CSD) activates trigeminovascular afferents, causing a long-lasting increase in middle meningeal arterial blood flow and polypeptide release within the dura mater.1 Reflex connections to the cranial parasympathetics form the trigeminoautonomic reflex. Activation of the cranial parasympathetics leads to release of vasoactive intestinal polypeptide (VIP) and to vasodilatation. Trigeminal sensory neurons contain substance P (SP), calcitonin gene-related peptide (CGRP), and neurokinin A.2 Stimulation of the trigeminal sensory neurons causes the release of SP and CGRP from sensory C-fiber terminals3 and the start of neurogenic inflammation,4 suggested by one study to occur in humans.5 The neuropeptides interact with the blood vessel wall, producing dilatation, plasma protein extravasation (PPE), …