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Review
. 2019 Aug;18(8):795-804.
doi: 10.1016/S1474-4422(19)30185-1. Epub 2019 May 31.

Migraine and the trigeminovascular system-40 years and counting

Messoud Ashina  1 , Jakob Møller Hansen  2 , Thien Phu Do  2 , Agustin Melo-Carrillo  3 , Rami Burstein  3 , Michael A Moskowitz  4
Affiliations
Review

Migraine and the trigeminovascular system-40 years and counting

Messoud Ashina et al. Lancet Neurol. 2019 Aug.

Abstract

The underlying causes of migraine headache remained enigmatic for most of the 20th century. In 1979, The Lancet published a novel hypothesis proposing an integral role for the neuropeptide-containing trigeminal nerve. This hypothesis led to a transformation in the migraine field and understanding of key concepts surrounding migraine, including the role of neuropeptides and their release from meningeal trigeminal nerve endings in the mechanism of migraine, blockade of neuropeptide release by anti-migraine drugs, and activation and sensitisation of trigeminal afferents by meningeal inflammatory stimuli and upstream role of intense brain activity. The study of neuropeptides provided the first evidence that antisera directed against calcitonin gene-related peptide (CGRP) and substance P could neutralise their actions. Successful therapeutic strategies using humanised monoclonal antibodies directed against CGRP and its receptor followed from these findings. Nowadays, 40 years after the initial proposal, the trigeminovascular system is widely accepted as having a fundamental role in this highly complex neurological disorder and provides a road map for future migraine therapies.

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Conflict of interest statement

Declaration of interests

MA has received personal fees from Alder BioPharmaceuticals, Allergan, Amgen, Alder, Eli Lilly, Novartis, and Teva. MA also participated in clinical trials as the principal investigator for Alder, Amgen, electroCore, Novartis, and Teva. MA also serves as an associated editor of Cephalalgia, associated editor of the Journal of Headache and Pain, is President-elect of the International Headache Society, and General Secretary of the European Headache Federation. RB has received grant support for his studies on migraine pathophysiology from Teva, Allergan, Dr Reddy, and Trigemina; he also serves as a consultant to Alder Biopharm, Allergan, Amgen, Autonomic Technologies, Avanir, Biohaven, Depomed, Dr Reddy, Electrocore, Johnson and Johnson, Neurolief, Percept, Pernix, Strategic Science and Technologies, Teva, Theranica, and Trigemina. RB and Beth Israel Deaconess Medical Center hold a provisional patent on the use of narrow band green light for the treatment of photophobia in migraine. MAM serves as a consultant for Pear Therapeutics and NeuroTrauma Sciences. JMH, TPD and AM-C declare that they have no competing interests.

Figures

Figure:
Figure:. Schematic overview of the trigeminovascular system
Adapted from Burstein et al. Thalamic trigeminovascular neurons project to a wide array of cortical areas that mediate symptoms associated with migraine, such as transient amnesia and cognitive decline, phonophobia, photophobia, and expressive aphasia. Inputs to SpV arise from meningeal dural blood vessels and pial blood vessels (not shown). Green: projections from SpV. Blue: thalamo-cortical projections. Yellow: afferent projections from meningeal blood vessels. Orange: afferent projections from cervical dorsal root ganglions.Peach: efferent projections to meningeal blood vessels. Au=Auditory cortex. ECT= ectorhinal cortex. Ins=insular cortex. LP=lateral posterior thalamic nucleus. M1=primary motor cortex. M2=secondary motor cortex. PAG=periaqueductal gray. PB=parabrachial nucleus. Po=posterior. PtA=parietal association cortex. Pul=pulvinar. RS=retrosplenial cortex. S1=primary somatosensory cortex. S2=secondary somatosensory cortex. SpV=spinal trigeminal nucleus. SSN=superior salivatory nucleus. V1=primary visual cortex. V2=secondary visual cortex. VPM=ventral posteromedial
See this image and copyright information in PMC

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