Pathophysiology of Migraine: A Disorder of Sensory Processing.
Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT1B/1Dreceptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1Freceptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; Department of Neurology, University of California, San Francisco, San Francisco, California; Department of Neurology, University of Hamburg-Eppendorf, Hamburg, Germany; and Department of Neurology, University Hospital Bern-Inselspital, University of Bern, Bern, Switzerland.
Peter J
PJ
Goadsby
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; Department of Neurology, University of California, San Francisco, San Francisco, California; Department of Neurology, University of Hamburg-Eppendorf, Hamburg, Germany; and Department of Neurology, University Hospital Bern-Inselspital, University of Bern, Bern, Switzerland.
Philip R
PR
Holland
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; Department of Neurology, University of California, San Francisco, San Francisco, California; Department of Neurology, University of Hamburg-Eppendorf, Hamburg, Germany; and Department of Neurology, University Hospital Bern-Inselspital, University of Bern, Bern, Switzerland.
Margarida
M
Martins-Oliveira
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; Department of Neurology, University of California, San Francisco, San Francisco, California; Department of Neurology, University of Hamburg-Eppendorf, Hamburg, Germany; and Department of Neurology, University Hospital Bern-Inselspital, University of Bern, Bern, Switzerland.
Jan
J
Hoffmann
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; Department of Neurology, University of California, San Francisco, San Francisco, California; Department of Neurology, University of Hamburg-Eppendorf, Hamburg, Germany; and Department of Neurology, University Hospital Bern-Inselspital, University of Bern, Bern, Switzerland.
Christoph
C
Schankin
Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom; Department of Neurology, University of California, San Francisco, San Francisco, California; Department of Neurology, University of Hamburg-Eppendorf, Hamburg, Germany; and Department of Neurology, University Hospital Bern-Inselspital, University of Bern, Bern, Switzerland.
Simon
S
Akerman
D000818:Animals; D001921:Brain / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D006801:Humans; D008881:Migraine Disorders / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D000096642:Receptor, Serotonin, 5-HT1F
D015740:Calcitonin Gene-Related Peptide; D018015:Receptors, Calcitonin Gene-Related Peptide; D011985:Receptors, Serotonin; D000096642:Receptor, Serotonin, 5-HT1F