Phosphodiesterase 3 inhibitor cilostazol induces migraine-like attacks via cyclic AMP increase
Phosphodiesterase 3 inhibitor cilostazol induces migraine-like attacks via cyclic AMP increase
复制标题
DOI：
10.1093/brain/awu244
复制
发表时间：
2014-11-01
期刊：
影响因子：
14.5
通讯作者：
Ashina, Messoud
中科院分区：
文献类型：
--
作者：
Guo, Song;Olesen, Jes;Ashina, Messoud
偏头痛发作的起始机制非常复杂，但可能涉及环AMP信号通路。目前尚不清楚细胞内环磷酸腺苷的积累是否会诱发偏头痛。我们研究了服用西洛他唑（导致环磷酸腺苷积累）是否可能诱发偏头痛发作。我们在一项双盲、安慰剂对照交叉研究中纳入了 14 名无先兆偏头痛患者。所有参与者在不同的两天内接受口服西洛他唑或安慰剂。我们通过问卷记录了偏头痛的特征、相关症状和服用救援药物的时间。西洛他唑诱导 12 名患者 (86%) 出现迟发性偏头痛样发作，而安慰剂组则有 2 名患者 (14%) (P = 0.002)。偏头痛样发作的中位时间为 6 小时（范围 3-11 小时）。患者报告说，这些发作模仿了他们通常的偏头痛发作，并且西洛他唑引起的发作对他们通常的偏头痛治疗有反应。服药时间中位数为 6 小时（范围 4-11 小时）。目前的研究表明细胞内环磷酸腺苷的积累在偏头痛的诱发中起着至关重要的作用。这一知识使我们对偏头痛发生的细胞内途径的理解又向前迈进了一步。
The initiating mechanisms of migraine attacks are very complex but may involve the cyclic AMP signalling pathway. It is unknown whether intracellular cyclic AMP accumulation induces migraine attacks. We investigated whether administration of cilostazol, which causes cyclic AMP accumulation, may induce migraine attacks. We included 14 migraine patients without aura in a double-blind, placebo-controlled crossover study. All participants received oral cilostazol or placebo on two separate days. We recorded migraine headache characteristics, associated symptoms and time of rescue medication intake using a questionnaire. Cilostazol induced delayed migraine-like attacks in 12 patients (86%) compared with two (14%) patients after placebo (P = 0.002). The median time to onset for migraine-like attacks was 6 h (range 3-11 h). Patients reported that the attacks mimicked their usual migraine attacks and that cilostazol-induced attacks responded to their usual migraine treatment. Median time of medication intake was 6 h (range 4-11 h). The present study suggests that intracellular cyclic AMP accumulation plays a crucial role in migraine induction. This knowledge is a further step in our understanding of the intracellular pathway of migraine initiation.