Tfelt-Hansen P, Daugaard D, Lassen L H, Iversen H K, Olesen J
Department of Neurology, Danish Headache Centre, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark.
Eur J Neurol. 2009 Oct;16(10):1106-11. doi: 10.1111/j.1468-1331.2009.02654.x. Epub 2009 Jul 14.
Glyceryl trinitrate (GTN) induces delayed migraine attacks in migraine patients. The purpose of this study was to investigate whether pre-treatment with prednisolon could decrease this effect of GTN.
In this double-blind, randomized and placebo-controlled, crossover study 15 migraineurs with migraine without aura were pre-treated with 150 mg of prednisolone or placebo followed by a 20-min infusion of GTN (0.5 ug/kg/min). One hour after the GTN-infusion, the participants were sent home, but continued to rate headache and possible associated symptoms by filling out a headache diary every hour for 12 h. There were two equal primary efficacy end-points: frequency of delayed migraine and intensity of delayed headache.
Nine patients experienced a GTN headache fulfilling the diagnostic criteria for migraine without aura on the placebo day compared with four patients on the prednisolone day (P = 0.14). Prednisolone pre-treatment did not alter the summed or peak immediate headache responses to GTN significantly (P = 0.08, P = 0.07), whereas the peak headache scores during the following 12 h were significantly lower after prednisolone pre-treatment (median peak score = 1, range 0-8) compared with placebo (median = 4, range 0-8) (P < 0.01). There was no difference between the two treatment days in the effect of GTN on blood flow velocity of the middle cerebral artery (a decrease) or on the dilation of the superficial temporal artery or the radial artery.
Pre-treatment with prednisolone did not reduce the immediate GTN-induced headache, did not inhibit the frequency of delayed headache but significantly decreased the intensity of delayed GTN-induced headache. These findings suggest that GTN causes induction of inflammatory mediators, and that this is the mechanism of delayed GTN-induced migraine. They also support a role of inflammatory mediators in spontaneous migraine attacks.
硝酸甘油(GTN)可诱发偏头痛患者出现延迟性偏头痛发作。本研究旨在调查泼尼松龙预处理是否能降低GTN的这种作用。
在这项双盲、随机、安慰剂对照的交叉研究中,15名无先兆偏头痛患者先接受150mg泼尼松龙或安慰剂预处理,随后静脉输注GTN(0.5μg/kg/min)20分钟。GTN输注1小时后,参与者被送回家,但需通过每小时填写头痛日记,持续12小时来评估头痛及可能的相关症状。有两个同等重要的主要疗效终点:延迟性偏头痛的发作频率和延迟性头痛的强度。
在安慰剂日,9名患者经历了符合无先兆偏头痛诊断标准的GTN头痛,而在泼尼松龙日这一数字为4名患者(P = 0.14)。泼尼松龙预处理并未显著改变对GTN的即时头痛总反应或峰值反应(P = 0.08,P = 0.07),然而,与安慰剂(中位数 = 4,范围0 - 8)相比,泼尼松龙预处理后接下来12小时内的头痛峰值评分显著更低(中位数峰值评分 = 1,范围0 - 8)(P < 0.01)。在GTN对大脑中动脉血流速度(降低)、颞浅动脉或桡动脉扩张的影响方面,两个治疗日之间没有差异。
泼尼松龙预处理并未减轻GTN即时诱发的头痛,未抑制延迟性头痛的发作频率,但显著降低了GTN诱发的延迟性头痛的强度。这些发现表明GTN可诱导炎症介质的产生,这是GTN诱发延迟性偏头痛的机制。它们还支持炎症介质在自发性偏头痛发作中的作用。