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Intravenous Endothelin-1 Infusion Does Not Induce Aura or Headache in Migraine Patients With Aura

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@article{cd187816d70748b49f840dccf6a1f5c1,
title = "Intravenous Endothelin-1 Infusion Does Not Induce Aura or Headache in Migraine Patients With Aura",
abstract = "OBJECTIVE: To investigate whether intravenously infused provokes migraine aura and migraine headache in migraine patients with aura.BACKGROUND: Migraine with aura has been associated with endothelial dysfunction and increased stroke risk. The initiating mechanism of migraine aura symptoms is not known. Experimental provocation of migraine headache using vasoactive peptides has provided tremendous advances in the understanding of migraine pathophysiology but substances that can induce migraine aura have not been identified. Endothelin-1 (ET-1), an endogenous, potent vasoconstrictor peptide released from the vascular endothelium, has been proposed to trigger migraine aura. This hypothesis is based on reports of increased plasma ET-1 levels early during the migraine attacks and the observation that ET-1 applied to the cortical surface potently induces the cortical spreading depolarization, the underlying electrophysiological phenomenon of migraine aura, in animals. Further, endothelial damage due to, for example, carotid puncture and vascular pathology is known to trigger aura episodes.METHODS: We investigated whether intravascular ET-1 would provoke migraine aura in patients. Using a two-way crossover, randomized, placebo-controlled, double-blind design, we infused high-dose (8 ng/kg/minutes for 20 minutes) intravenous ET-1 in patients with migraine with typical aura. The primary end-point was the difference in incidence of migraine aura between ET-1 and placebo. Experiments were carried out at a public tertiary headache center (Danish Headache Center, Rigshospitalet Glostrup, Denmark).RESULTS: Fourteen patients received intravenous ET-1. No patients reported migraine aura symptoms or migraine headache during or up to 24 hours following the ET-1 infusion. Four patients reported mild to moderate headache only on the ET-1 day, 3 patients reported moderate headache on the placebo day, and 1 patient reported mild headache on both days. No serious adverse events occurred during or after infusion.CONCLUSIONS: Provocation of migraine aura by procedures or conditions involving vascular irritation is unlikely to be mediated by ET-1.",
keywords = "endothelium, human, provocation, trigger, vascular",
author = "Anders Hougaard and Samaira Younis and Afrim Iljazi and Kazutaka Sugimoto and Cenk Ayata and Messoud Ashina",
note = "{\textcopyright} 2020 American Headache Society.",
year = "2020",
month = apr,
doi = "10.1111/head.13753",
language = "English",
volume = "60",
pages = "724--734",
journal = "Headache",
issn = "0017-8748",
publisher = "Wiley-Blackwell Publishing, Inc",
number = "4",

}

RIS

TY - JOUR

T1 - Intravenous Endothelin-1 Infusion Does Not Induce Aura or Headache in Migraine Patients With Aura

AU - Hougaard, Anders

AU - Younis, Samaira

AU - Iljazi, Afrim

AU - Sugimoto, Kazutaka

AU - Ayata, Cenk

AU - Ashina, Messoud

N1 - © 2020 American Headache Society.

PY - 2020/4

Y1 - 2020/4

N2 - OBJECTIVE: To investigate whether intravenously infused provokes migraine aura and migraine headache in migraine patients with aura.BACKGROUND: Migraine with aura has been associated with endothelial dysfunction and increased stroke risk. The initiating mechanism of migraine aura symptoms is not known. Experimental provocation of migraine headache using vasoactive peptides has provided tremendous advances in the understanding of migraine pathophysiology but substances that can induce migraine aura have not been identified. Endothelin-1 (ET-1), an endogenous, potent vasoconstrictor peptide released from the vascular endothelium, has been proposed to trigger migraine aura. This hypothesis is based on reports of increased plasma ET-1 levels early during the migraine attacks and the observation that ET-1 applied to the cortical surface potently induces the cortical spreading depolarization, the underlying electrophysiological phenomenon of migraine aura, in animals. Further, endothelial damage due to, for example, carotid puncture and vascular pathology is known to trigger aura episodes.METHODS: We investigated whether intravascular ET-1 would provoke migraine aura in patients. Using a two-way crossover, randomized, placebo-controlled, double-blind design, we infused high-dose (8 ng/kg/minutes for 20 minutes) intravenous ET-1 in patients with migraine with typical aura. The primary end-point was the difference in incidence of migraine aura between ET-1 and placebo. Experiments were carried out at a public tertiary headache center (Danish Headache Center, Rigshospitalet Glostrup, Denmark).RESULTS: Fourteen patients received intravenous ET-1. No patients reported migraine aura symptoms or migraine headache during or up to 24 hours following the ET-1 infusion. Four patients reported mild to moderate headache only on the ET-1 day, 3 patients reported moderate headache on the placebo day, and 1 patient reported mild headache on both days. No serious adverse events occurred during or after infusion.CONCLUSIONS: Provocation of migraine aura by procedures or conditions involving vascular irritation is unlikely to be mediated by ET-1.

AB - OBJECTIVE: To investigate whether intravenously infused provokes migraine aura and migraine headache in migraine patients with aura.BACKGROUND: Migraine with aura has been associated with endothelial dysfunction and increased stroke risk. The initiating mechanism of migraine aura symptoms is not known. Experimental provocation of migraine headache using vasoactive peptides has provided tremendous advances in the understanding of migraine pathophysiology but substances that can induce migraine aura have not been identified. Endothelin-1 (ET-1), an endogenous, potent vasoconstrictor peptide released from the vascular endothelium, has been proposed to trigger migraine aura. This hypothesis is based on reports of increased plasma ET-1 levels early during the migraine attacks and the observation that ET-1 applied to the cortical surface potently induces the cortical spreading depolarization, the underlying electrophysiological phenomenon of migraine aura, in animals. Further, endothelial damage due to, for example, carotid puncture and vascular pathology is known to trigger aura episodes.METHODS: We investigated whether intravascular ET-1 would provoke migraine aura in patients. Using a two-way crossover, randomized, placebo-controlled, double-blind design, we infused high-dose (8 ng/kg/minutes for 20 minutes) intravenous ET-1 in patients with migraine with typical aura. The primary end-point was the difference in incidence of migraine aura between ET-1 and placebo. Experiments were carried out at a public tertiary headache center (Danish Headache Center, Rigshospitalet Glostrup, Denmark).RESULTS: Fourteen patients received intravenous ET-1. No patients reported migraine aura symptoms or migraine headache during or up to 24 hours following the ET-1 infusion. Four patients reported mild to moderate headache only on the ET-1 day, 3 patients reported moderate headache on the placebo day, and 1 patient reported mild headache on both days. No serious adverse events occurred during or after infusion.CONCLUSIONS: Provocation of migraine aura by procedures or conditions involving vascular irritation is unlikely to be mediated by ET-1.

KW - endothelium

KW - human

KW - provocation

KW - trigger

KW - vascular

U2 - 10.1111/head.13753

DO - 10.1111/head.13753

M3 - Journal article

C2 - 31994720

VL - 60

SP - 724

EP - 734

JO - Headache

JF - Headache

SN - 0017-8748

IS - 4

ER -

ID: 59482976