Introduction

Preclinical data implicate large conductance calcium-activated potassium (BK_Ca) channels in the pathogenesis of headache and migraine, but the exact role of these channels is still unknown. Here, we investigated whether opening of BK_Ca channels would cause headache and vascular effects in healthy volunteers.

Methods

In a randomized, double-blind, placebo-controlled, cross-over study, 21 healthy volunteers aged 18–39 years were randomly allocated to receive an intravenous infusion of 0.05 mg/min BK_Ca channel opener MaxiPost and placebo on two different days. The primary endpoints were the difference in incidence of headache and the difference in area under the curve (AUC) for headache intensity scores (0–12 hours) and for middle cerebral artery blood flow velocity (V_MCA) (0–2 hours) between MaxiPost and placebo. The secondary endpoints were the differences in area under the curve for superficial temporal artery and radial artery diameter (0–2 hours) between MaxiPost and placebo.

Results

Twenty participants completed the study. Eighteen participants (90%) developed headache after MaxiPost compared with six (30%) after placebo (p = 0.0005); the difference of incidence is 60% (95% confidence interval 36–84%). The area under the curve for headache intensity (AUC_{0–12 hours}, p = 0.0003), for mean V_MCA (AUC_{0–2 hours}, p = 0.0001), for superficial temporal artery diameter (AUC_{0–2 hours}, p = 0.003), and for radial artery diameter (AUC_{0–2 hours}, p = 0.03) were significantly larger after MaxiPost compared to placebo.

Conclusion

MaxiPost caused headache and dilation in extra- and intracerebral arteries. Our findings suggest a possible role of BK_Ca channels in headache pathophysiology in humans. ClinicalTrials.gov, ID: NCT03887325.

中文翻译：

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BKCa 通道的开放会改变脑血流动力学并导致健康志愿者头痛。

介绍

临床前数据表明大电导钙激活钾 (BK _Ca ) 通道与头痛和偏头痛的发病机制有关，但这些通道的确切作用尚不清楚。在这里，我们调查了 BK _Ca通道的开放是否会导致健康志愿者的头痛和血管影响。

方法

在一项随机、双盲、安慰剂对照、交叉研究中，21 名年龄在 18-39 岁之间的健康志愿者被随机分配在两个不同的日子接受 0.05 mg/min BK _Ca通道开放剂 MaxiPost 和安慰剂的静脉输注。主要终点是头痛发生率的差异以及头痛强度评分（0-12 小时）和大脑中动脉血流速度（V _MCA）（0-2 小时）曲线下面积 (AUC ) 的差异。 MaxiPost 和安慰剂。次要终点是 MaxiPost 和安慰剂之间颞浅动脉和桡动脉直径（0-2 小时）曲线下面积的差异。

结果

二十名参与者完成了这项研究。MaxiPost 后有 18 名参与者 (90%) 出现头痛，而安慰剂后有 6 名参与者 (30%) ( p  = 0.0005)；发生率的差异为 60%（95% 置信区间为 36-84%）。头痛强度曲线下面积（AUC _{0-12 小时}，p  = 0.0003），平均 V _MCA（AUC _{0-2 小时}，p  = 0.0001），颞浅动脉直径（AUC _{0-2 小时}，p  = 0.003），并且 与安慰剂相比，MaxiPost 后桡动脉直径（AUC _{0-2 小时}，p = 0.03）显着更大。

结论

MaxiPost 引起头痛和脑外和脑内动脉扩张。我们的研究结果表明 BK _Ca通道可能在人类头痛病理生理学中发挥作用。ClinicalTrials.gov，ID：NCT03887325。