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PATHOPHYSIOLOGY OF MIGRAINE: A DISORDER OF SENSORY PROCESSING

Published on Apr 1, 2017in Physiological Reviews24.25
· DOI :10.1152/physrev.00034.2015
Peter J. Goadsby111
Estimated H-index: 111
,
Philip R. Holland27
Estimated H-index: 27
(UCSF: University of California, San Francisco)
+ 3 AuthorsSimon Akerman29
Estimated H-index: 29
(UCSF: University of California, San Francisco)
Sources
Abstract
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/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5 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.
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  • References (872)
  • Citations (220)
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References872
Newest
#1Catherine D. Chong (Mayo Clinic)H-Index: 12
#2Nathan Gaw (ASU: Arizona State University)H-Index: 4
Last. Todd J. Schwedt (Mayo Clinic)H-Index: 28
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BackgroundThis study used machine-learning techniques to develop discriminative brain-connectivity biomarkers from resting-state functional magnetic resonance neuroimaging (rs-fMRI) data that distinguish between individual migraine patients and healthy controls.MethodsThis study included 58 migraine patients (mean age = 36.3 years; SD = 11.5) and 50 healthy controls (mean age = 35.9 years; SD = 11.0). The functional connections of 33 seeded pain-related regions were used as input for a brain cla...
20 CitationsSource
#1J. GoldsteinH-Index: 1
#2Cgh DahlöfH-Index: 9
Last. Timothy J. SteinerH-Index: 49
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Alniditan is a new 5HT1D receptor agonist, belonging to a different chemical class from sumatriptan and other indole derivatives used or being developed for the treatment of acute migraine. In a multinational double-blind randomized parallel-groups dose-finding trial, alniditan was given subcutaneously in hospital to patients with migraine headache of moderate or severe intensity at doses of 0.8 mg (n = 44), 1.0 mg (n = 42), 1.2 mg (n=46) and 1.4 mg (n=39). Efficacy, tolerability and safety of e...
1 CitationsSource
The International Symposium in London, organized by The Migraine Trust, has been a regular biennial event for over twenty years. It has always provided an excellent forum for the dissemination of the latest observations in headache research. Now, through the generous cooperation of the Editor, the Trust is delighted to have the opportunity for the research to be presented in September to reach a wider audience by publication of the abstracts in this journal.
1 CitationsSource
#2Simon Akerman (NYU: New York University)H-Index: 29
Last. Peter J. GoadsbyH-Index: 111
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AbstractMigraine is a painful neurologic disorder with premonitory symptomatology that can include disturbed appetite. Migraine pathophysiology involves abnormal activation of trigeminocervical complex (TCC) neurons. Neuropeptide Y (NPY) is synthesized in the brain and is involved in pain modulation
14 CitationsSource
#1N. J. Giffin (RUH: Royal United Hospital)H-Index: 12
#2Richard B. LiptonH-Index: 97
Last. Peter J. Goadsby (Wellcome Trust)H-Index: 111
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Objective: To report migraine postdrome symptoms in patients who report nonheadache symptoms as part of their attacks. Methods: A prospective daily electronic diary study was conducted over 3 months in 120 patients with migraine. Nonheadache symptoms before, during, and after headache were collected on a daily basis. Visual analogue scales were used to capture the overall level of functioning and the severity of the headache. The postdrome was defined as the time from resolution of troublesome h...
36 CitationsSource
Functional imaging using positron emission tomography and later functional magnetic resonance imaging revealed a particular brainstem area that is believed to be specifically activated in migraine during, but not outside of the attack, and consequently has been coined the ‘migraine generator’ . However, the pathophysiological concept behind this term is not undisputed and typical migraine premonitory symptoms such as fatigue and yawning, but also a typical association of attacks to circadian and...
130 CitationsSource
#1Anna P. Andreou (UCSF: University of California, San Francisco)H-Index: 16
#2Philip R. Holland ('KCL': King's College London)H-Index: 27
Last. Peter J. Goadsby (UCSF: University of California, San Francisco)H-Index: 111
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A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activ...
30 CitationsSource
#1Christoph J. Schankin (University of Bern)H-Index: 21
#2Farooq H. Maniyar (UCSF: University of California, San Francisco)H-Index: 8
Last. Peter J. Goadsby (UCSF: University of California, San Francisco)H-Index: 111
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SEE DREIER DOI 101093/AWW112 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: For many decades a breakdown of the blood-brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood-brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced m...
33 CitationsSource
#1Maggie W. Waung (UCSF: University of California, San Francisco)H-Index: 5
#2Simon Akerman (UCSF: University of California, San Francisco)H-Index: 29
Last. Peter J. Goadsby (UCSF: University of California, San Francisco)H-Index: 111
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Introduction Many patients suffering from migraine gain little relief from existing treatments partly because many existing acute and preventive therapies used in migraine have been adopted from other neurologic conditions such as depression or epilepsy. Here, we present data supporting a new migraine-specific target, the mGlu5 receptor. Methods We studied the effect of mGlu5 blockade using ADX10059, on neuronal firing in the trigeminocervical complex (TCC) and durovascular effects of nociceptiv...
16 CitationsSource
#1Tiffini Voss (MSD: Merck & Co.)H-Index: 9
#2Richard B. Lipton (Albert Einstein College of Medicine)H-Index: 97
Last. David Michelson (MSD: Merck & Co.)H-Index: 48
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AimThe aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP-RA), for the acute treatment of migraine....
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#1Zhaoxia Qin (ECNU: East China Normal University)H-Index: 1
#2Jingjing Su (SJTU: Shanghai Jiao Tong University)H-Index: 10
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BACKGROUND: Migraine is a severe and disabling brain disorder, and the exact neurological mechanisms remain unclear. Migraineurs have altered pain perception, and headache attacks disrupt their sensory information processing and sensorimotor integration. The altered functional connectivity of sub-regions of sensorimotor brain areas with other brain cortex associated with migraine needs further investigation. METHODS: Forty-eight migraineurs without aura during the interictal phase and 48 age- an...
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#1M Torres-Ferrus (Autonomous University of Barcelona)
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Chronic migraine is a neurological disorder characterized by 15 or more headache days per month of which at least 8 days show typical migraine features. The process that describes the development from episodic migraine into chronic migraine is commonly referred to as migraine transformation or chronification. Ample studies have attempted to identify factors associated with migraine transformation from different perspectives. Understanding CM as a pathological brain state with trigeminovascular p...
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IntroductionCurrent treatment options for the prevention of cluster headache are largely unsatisfactory. The therapies have a limited evidence base and often significant side effects issues. The involvement of the calcitonin gene-related peptide (CGRP) pathway in primary headache disorders, especially migraine, had led to recent success in the development of new migraine therapies. The CGRP pathway also plays a role in the pathophysiology of cluster headache, so CGRP pathway monoclonal antibodie...
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Migraine is the third most prevalent disease worldwide and current therapies provide only partial relief. Greater insight into molecular migraine mechanisms would create novel therapies. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on microtubule dynamicity. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, α-tubulin. We use validated models of chronic migraine to show that HDAC6-inhibition is an effective migr...
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#1Samar S. Ayache (University of Paris)H-Index: 20
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Migraine, a benign yet disturbing condition, is one of the frequent neurological disorders, affecting up to 15–20% of the worldwide population [...]
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Herbal treatments are often used as a treatment for migraine. Therefore, an evaluation of their safety and efficacy is important. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and Cochrane Collaboration's tool for assessing the risk of bias, a systematic literature review of randomised, controlled human trials assessing the effects of herbal treatments delivered as a single ingredient for the acute or prophylactic treatment of migraine were conducted...
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#1Y. Lévêque (UCBL: Claude Bernard University Lyon 1)
#2Rémy Masson (UCBL: Claude Bernard University Lyon 1)H-Index: 2
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BACKGROUND: Attention is the process which enables to preferentially select salient or relevant stimuli and to attenuate the response to irrelevant incoming stimuli. Migraine is characterized by both attentional alterations and an abnormal sensory processing to external stimulations. The aim of the study was to investigate potential interactions between self-perceived attentional difficulties and sensory hypersensitivity in migraine patients. METHODS: Forty-six episodic migraineurs without aura ...
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