Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Glostrup, Denmark.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Headache. 2020 Apr;60(4):724-734. doi: 10.1111/head.13753. Epub 2020 Jan 29.
To investigate whether intravenously infused provokes migraine aura and migraine headache in migraine patients with aura.
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.
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).
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.
Provocation of migraine aura by procedures or conditions involving vascular irritation is unlikely to be mediated by ET-1.
探讨静脉内输注是否会诱发有先兆偏头痛患者的偏头痛先兆和偏头痛头痛。
有先兆偏头痛与血管内皮功能障碍和中风风险增加有关。偏头痛先兆症状的起始机制尚不清楚。使用血管活性肽实验性诱发偏头痛头痛已经在偏头痛病理生理学的理解方面取得了巨大进展，但尚未确定能够诱发偏头痛先兆的物质。内皮素-1（ET-1）是一种内源性的、强效的血管收缩肽，从血管内皮释放出来，据报道，它可以触发偏头痛先兆。这一假说基于偏头痛发作早期血浆 ET-1 水平升高的报道，以及观察到 ET-1 施加于皮质表面时在动物中强烈诱导偏头痛先兆的皮质扩散性去极化，这是偏头痛先兆的潜在电生理现象。此外，已知血管内皮损伤，例如颈动脉穿刺和血管病理学，会引发先兆发作。
我们研究了血管内 ET-1 是否会在偏头痛患者中诱发偏头痛先兆。采用双盲、随机、安慰剂对照的双向交叉设计，我们在有典型先兆的偏头痛患者中静脉内输注高剂量（8ng/kg/min 持续 20 分钟）ET-1。主要终点是 ET-1 和安慰剂之间偏头痛先兆发生率的差异。实验在一家公立三级头痛中心（丹麦头痛中心，格罗斯特鲁普的里格医院，丹麦）进行。
14 名患者接受了静脉内 ET-1 输注。在 ET-1 输注期间或之后 24 小时内，没有患者报告偏头痛先兆症状或偏头痛头痛。4 名患者仅在 ET-1 日报告轻度至中度头痛，3 名患者在安慰剂日报告中度头痛，1 名患者在两天都报告轻度头痛。输注过程中和输注后均未发生严重不良事件。
涉及血管刺激的程序或条件诱发偏头痛先兆不太可能由 ET-1 介导。
