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  • Review Article
  • Published:

Human models of migraine — short-term pain for long-term gain

Nature Reviews Neurology volume 13, pages 713–724 (2017)Cite this article

Subjects

Key Points

  • A key feature of migraine is that various factors can trigger an attack, thereby providing a unique opportunity to investigate disease mechanisms by experimentally inducing migraine attacks

  • Experimental studies in humans have provided evidence that a number of signalling compounds, including nitric oxide and the neuropeptides CGRP and PACAP, are involved in migraine pathophysiology

  • Migraine can be elicited by activation of cGMP and cAMP signalling pathways

  • Provocation studies have predicted the efficacy of CGRP-based small molecules and antibody-based antimigraine treatment

  • Migraine provocation by PACAP suggests that the PACAP receptor is a novel target for migraine treatment

  • Experimental studies in humans, combined with advanced neuroimaging, will help to improve our understanding of basic migraine neurobiology and guide the search for new mechanism-based antimigraine drugs

Abstract

Migraine is a complex disorder characterized by recurrent episodes of headache, and is one of the most prevalent and disabling neurological disorders. A key feature of migraine is that various factors can trigger an attack, and this phenomenon provides a unique opportunity to investigate disease mechanisms by experimentally inducing migraine attacks. In this Review, we summarize the existing experimental models of migraine in humans, including those that exploit nitric oxide, histamine, neuropeptide and prostaglandin signalling. We describe the development and use of these models in the discovery of molecular pathways that are responsible for initiation of migraine attacks. Combining experimental human models with advanced imaging techniques might help to identify biomarkers of migraine, and in the ongoing search for new and better migraine treatments, human models will have a key role in the discovery of future targets for more-specific and more-effective mechanism-based antimigraine drugs.

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Figure 1: The set-up of an experimental human migraine study.
Figure 2: Immediate and delayed attacks after migraine induction.
Figure 3: The trigeminovascular system.

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  1. Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, DK-2600, Denmark

    Messoud Ashina, Jakob Møller Hansen, Bára Oladóttir á Dunga & Jes Olesen

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All authors researched data for the article, discussed the content, wrote the text, and reviewed and edited the manuscript before submission.

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M. Ashina is a consultant, speaker or scientific advisor for Allergan, Amgen, Alder, ATI, Eli Lilly, Novartis and Teva. The other authors declare no competing interests.

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Ashina, M., Hansen, J., á Dunga, B. et al. Human models of migraine — short-term pain for long-term gain. Nat Rev Neurol 13, 713–724 (2017). https://doi.org/10.1038/nrneurol.2017.137

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