西地那非对伴先兆偏头痛患者的头痛及诱发先兆的作用。

The headache and aura-inducing effects of sildenafil in patients with migraine with aura.

作者信息

Butt Jawad H, S Eddelien Heidi, Kruuse Christina

机构信息

Department of Neurology, Neurovascular Research Unit, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.

出版信息

Cephalalgia. 2022 Sep;42(10):984-992. doi: 10.1177/03331024221088998. Epub 2022 Mar 25.

DOI:10.1177/03331024221088998

PMID:35332812

Abstract

INTRODUCTION

It has not been established if migraine headache and migraine aura share common pathophysiological mechanisms. Sildenafil, a phosphodiesterase-5 inhibitor, causes cGMP accumulation and provokes migraine-like headache in patients with migraine without aura. We investigated if sildenafil induced aura and migraine-like headache in patients with migraine with aura.

METHODS

In a randomized, double-blinded, placebo-controlled crossover study, 16 patients with migraine with aura (of whom 11 patients exclusively had attacks of migraine with aura) received 100 mg sildenafil or placebo on two separate days. The development, duration, and characteristics of aura and headache were recorded using a questionnaire. The primary outcome was the incidence of migraine aura.

RESULTS

Aura symptoms were induced in three patients (19%) after sildenafil and none after placebo (P < 0.001). After administration of sildenafil, 12 patients (75%) developed headache compared with two patients (12.5%) after placebo (Fisher's exact test, P < 0.001). The headache in nine patients (56%) after sildenafil and one patient (6%) after placebo fulfilled the criteria for migraine-like attacks (Fisher's exact test, P = 0.002). All patients, who fulfilled the criteria for migraine-like attacks, reported that the attack mimicked the headache phase during their usual migraine attacks.

DISCUSSION

Sildenafil have a moderate migraine headache-inducing and a modest aura-inducing effect in patients with migraine with aura, even in those who exclusively experienced attacks of migraine with aura in their spontaneous attacks. These findings suggest that accumulation of cGMP by PDE5-inhibition do not play any significant role in the initiation of migraine aura and refute the hypothesis of sildenafil being a tool for pharmacological provocation of this phenomenon. These findings further support dissociation between the aura and the headache phase. ClinicalTrials.gov - NCT02795351.

摘要

引言

偏头痛性头痛和偏头痛先兆是否共享共同的病理生理机制尚未明确。西地那非是一种磷酸二酯酶-5抑制剂，可导致环磷酸鸟苷（cGMP）蓄积，并在无先兆偏头痛患者中引发类似偏头痛的头痛。我们研究了西地那非是否会在有先兆偏头痛患者中诱发先兆和类似偏头痛的头痛。

方法

在一项随机、双盲、安慰剂对照的交叉研究中，16例有先兆偏头痛患者（其中11例仅发作有先兆偏头痛）在两个不同日期分别接受100毫克西地那非或安慰剂。使用问卷记录先兆和头痛的发生、持续时间及特征。主要结局是偏头痛先兆的发生率。

结果

服用西地那非后3例患者（19%）出现先兆症状，服用安慰剂后无患者出现（P<0.001）。服用西地那非后，12例患者（75%）出现头痛，而服用安慰剂后为2例患者（12.5%）（Fisher精确检验，P<0.001）。服用西地那非后9例患者（56%）的头痛和服用安慰剂后1例患者（6%）的头痛符合类似偏头痛发作的标准（Fisher精确检验，P=0.002）。所有符合类似偏头痛发作标准的患者均报告发作类似于其通常偏头痛发作时的头痛阶段。

讨论

西地那非在有先兆偏头痛患者中具有中度的诱发偏头痛性头痛和轻度的诱发先兆的作用，即使是那些在自发发作中仅经历有先兆偏头痛发作的患者。这些发现表明，通过抑制磷酸二酯酶5使cGMP蓄积在偏头痛先兆的起始过程中未发挥任何重要作用，并反驳了西地那非是药理学激发这一现象的工具的假说。这些发现进一步支持了先兆和头痛阶段之间的分离。ClinicalTrials.gov - NCT02795351。