title: Basic mechanisms of migraine and its acute treatment.
abstract: Migraine is a neurovascular disorder characterized by recurrent unilateral headaches accompanied by nausea, vomiting, photophobia and phonophobia. Current theories suggest that the initiation of a migraine attack involves a primary event in the central nervous system (CNS), probably involving a combination of genetic changes in ion channels and environmental changes, which renders the individual more sensitive to environmental factors; this may, in turn, result in a wave of cortical spreading depression (CSD) when the attack is initiated. Genetically, migraine is a complex familial disorder in which the severity and the susceptibility of individuals are most likely governed by several genes that vary between families. Early PET studies have suggested the involvement of a migraine active region in the brainstem. Migraine headache is associated with trigeminal nerve activation and calcitonin gene-related peptide (CGRP) release from the trigeminovascular system. Administration of triptans (5-HT(1B/1D) receptor agonists) causes the headache to subside and the levels of CGRP to normalize. Moreover, administration of CGRP receptor antagonists aborts the headache. Recent immunohistochemical and pharmacological results suggest that the trigeminal system has receptors for CGRP; further, 5-HT(1B/1D) receptors, which inhibit the action of CGRP in pain transmission when activated, have been demonstrated. This offers an explanation for the treatment response. The present review provides an updated analysis of the basic mechanisms involved in the pathophysiology of migraine and the various pharmacological approaches (including 5-HT(1B/1D) receptor agonists, CGRP receptor antagonists and glutamate receptor antagonists) that have shown efficacy for the acute treatment of this disorder.
authors.affiliation: Department of Internal Medicine, Lund University Hospital, S-221 85 Lund, Sweden. lars.edvinsson@med.lu.se
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
authors.forename: Antoinette
authors.initials: A
authors.lastname: MaassenVanDenBrink
mesh_terms: D001341:Autonomic Nervous System / Q000502:physiology; D001808:Blood Vessels / Q000294:innervation; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D012018:Reflex; D014276:Trigeminal Nerve / Q000502:physiology
chemical_list: D015740:Calcitonin Gene-Related Peptide