Abstract

Despite considerable research into the pathogenesis of migraine, the pathophysiological mechanisms that underlie migraine headache remain poorly understood. Migraine is thought to be caused by a disten- sion of meningeal blood vessels, the activation of trigeminal sensory neurones and the development of a central sensitization within the trigeminal nucleus caudalis. Neurogenic inflammation within the menin- geal vasculature is elicited by neuropeptide release from trigeminal sensory fibers and characterized by plasma protein extravasation, vasodilation and histamine release from mast cells. Antimigraine agents such as ergots, triptans, opioids, and valproate inhibit neurogenic dural extravasation, suggesting that this activity may be a predictor of potential clinical efficacy of novel agents. Alternatively, it has been sugges- ted that neurogenic vasodilation of meningeal blood vessels could be also a key component of the inflammatory process during migraine headache. This view is supported by the observation that calcitonin gene-related peptide(CGRP), a potent vasodilator, has been detected in increased amounts in external jugular venous blood during migraine attacks and normalized by successful sumatriptan treatment. Nitric oxide donor glyceryl trinitrate provokes delayed migraine attacks when infused into migraineuers and results in NF-kB activation, iNOS expression and subsequent dural inflammation. These findings suggest that CGRP and NO release with associated neurogenic dural inflammation may be important in the generation of migraine headache. Targeting inflammatory response by selectively inhibiting mediators of neurogenic inflammation offers a new approach to the pharmacological treatment of migraine. Korean Journal of Headache 4(1):1-6, 2003