The Role of Endothelin in the Pathophysiology of Migraine—a Systematic Review

  • Afrim Iljazi
  • Cenk Ayata
  • Messoud Ashina
  • Anders Hougaard
Episodic Migraine (S Nahas, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Episodic Migraine


Purpose of Review

Vasoactive peptides play a key role in the attack-initiating cascade of migraine. Recent studies have highlighted a potentially important role for endothelin-1, a potent vasoconstrictor peptide, in migraine pathophysiology. Here, we review the current data on endothelin’s involvement in migraine.

Recent Findings

We identified 23 articles. Nine studies reported on endothelin-1 plasma concentrations in patients with migraine, eight studies investigated relevant genetic associations, five studies investigated endothelin-1 and spreading depression in animals, and one randomized controlled clinical trial tested the efficacy of an endothelin antagonist in the acute treatment of migraine in patients both with and without aura. Elevated endothelin-1 plasma levels have been reported in the early phase of migraine attacks. Genetic abnormalities related to the endothelin type A receptor have been reported in migraineurs. Endothelin-1 potently induces spreading depression in animals, which may explain the connection between endothelial irritation and migraine aura.


Endothelin-1 could be a primary factor in the attack-triggering cascade of migraine attacks with and without aura. Additional studies in humans and animal models are needed to further elucidate the role of endothelin-1 in migraine.


Endothelium Vascular Aura Spreading depression 


Funding Information

The study was supported by the Lundbeck Foundation (R221-2016-1002 and R155-2014-171), the Frimodt-Heineke Foundation, and the Cool Sorption Foundation.

Compliance with Ethical Standards

Conflict of Interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Afrim Iljazi
    • 1
  • Cenk Ayata
    • 2
  • Messoud Ashina
    • 1
    • 3
  • Anders Hougaard
    • 1
  1. 1.Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical SciencesUniversity of CopenhagenGlostrupDenmark
  2. 2.Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General HospitalHarvard Medical SchoolCharlestownUSA
  3. 3.Institute of Clinical Medicine, Faculty of Health and Medical ScienceUniversity of CopenhagenCopenhagenDenmark

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