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2017 ; 97
(2
): 553-622
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Pathophysiology of Migraine: A Disorder of Sensory Processing
#MMPMID28179394
Goadsby PJ
; Holland PR
; Martins-Oliveira M
; Hoffmann J
; Schankin C
; Akerman S
Physiol Rev
2017[Apr]; 97
(2
): 553-622
PMID28179394
show ga
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-HT(1B/1D) receptor agonists; gepants, calcitonin gene-related peptide (CGRP)
receptor antagonists; ditans, 5-HT(1F) receptor agonists, CGRP mechanisms
monoclonal antibodies; and glurants, mGlu(5) modulators; 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.
free
free
free
