Abstract：
BACKGROUND: The cAMP and cGMP pathways are implicated in the initiation of migraine attacks, but their interactions remain unclear. Calcitonin gene-related peptide (CGRP) triggers migraine attacks via cAMP, whereas the phosphodiesterase-5 inhibitor sildenafil induces migraine attacks via cGMP. Our objective was to investigate whether sildenafil could induce migraine attacks in individuals with migraine pre-treated with the CGRP-receptor antibody erenumab.
METHODS: In this randomized, double-blind, placebo-controlled, cross-over study, adults with migraine without aura received a single subcutaneous injection of 140 mg erenumab on day 1. They were then randomized to receive sildenafil 100 mg or placebo on two experimental days, each separated by at least one week, between days 8 and 21. The primary endpoint was the difference in the incidence of migraine attacks between sildenafil and placebo during the 12-h observation period after administration.
RESULTS: In total, 16 participants completed the study. Ten participants (63%) experienced a migraine attack within 12 h after sildenafil administration compared to three (19%) after placebo (p = 0.016). The median headache intensity was higher after sildenafil than after placebo (area under the curve (AUC) for the 12-h observation period, p = 0.026). Furthermore, sildenafil induced a significant decrease in mean arterial blood pressure (AUC, p = 0.026) and a simultaneous increase in heart rate (AUC, p < 0.001) during the first hour after administration compared to placebo.
CONCLUSIONS: These findings provide evidence that migraine induction via the cGMP pathway can occur even under CGRP receptor blockade.
BACKGROUND: ClinicalTrials.gov: Identifier NCT05889455.
METHODS: In this randomized, double-blind, placebo-controlled, cross-over study, adults with migraine without aura received a single subcutaneous injection of 140 mg erenumab on day 1. They were then randomized to receive sildenafil 100 mg or placebo on two experimental days, each separated by at least one week, between days 8 and 21. The primary endpoint was the difference in the incidence of migraine attacks between sildenafil and placebo during the 12-h observation period after administration.
RESULTS: In total, 16 participants completed the study. Ten participants (63%) experienced a migraine attack within 12 h after sildenafil administration compared to three (19%) after placebo (p = 0.016). The median headache intensity was higher after sildenafil than after placebo (area under the curve (AUC) for the 12-h observation period, p = 0.026). Furthermore, sildenafil induced a significant decrease in mean arterial blood pressure (AUC, p = 0.026) and a simultaneous increase in heart rate (AUC, p < 0.001) during the first hour after administration compared to placebo.
CONCLUSIONS: These findings provide evidence that migraine induction via the cGMP pathway can occur even under CGRP receptor blockade.
BACKGROUND: ClinicalTrials.gov: Identifier NCT05889455.
摘要：
背景：cAMP和cGMP通路与偏头痛的发作有关，但它们的相互作用仍不清楚。降钙素基因相关肽（CGRP）通过cAMP触发偏头痛发作，而磷酸二酯酶-5抑制剂西地那非通过cGMP诱导偏头痛发作.我们的目的是研究西地那非是否可以诱导使用CGRP受体抗体erenumab预处理的偏头痛患者的偏头痛发作。
方法：在本随机分组中，双盲,安慰剂对照,交叉研究，无先兆偏头痛患者在第1天接受单次皮下注射140mgerenumab.然后他们在两个实验日随机接受西地那非100毫克或安慰剂，每个间隔至少一周，在第8天和第21天之间。主要终点是西地那非和安慰剂在给药后12小时观察期间偏头痛发作发生率的差异。
结果：总计，16名参与者完成了这项研究。10名参与者（63％）在服用西地那非后12小时内经历了偏头痛发作，而安慰剂后3名（19％）（p=0.016）。西地那非后的中位头痛强度高于安慰剂后（12小时观察期的曲线下面积（AUC），p=0.026)。此外，西地那非诱导平均动脉血压显著降低(AUC，p=0.026）和同时增加心率（AUC，与安慰剂相比，p<0.001）。
结论：这些发现提供了证据，证明即使在CGRP受体阻断下，也可以通过cGMP途径诱导偏头痛。
背景：ClinicalTrials.gov：标识符NCT05889455。
方法：在本随机分组中，双盲,安慰剂对照,交叉研究，无先兆偏头痛患者在第1天接受单次皮下注射140mgerenumab.然后他们在两个实验日随机接受西地那非100毫克或安慰剂，每个间隔至少一周，在第8天和第21天之间。主要终点是西地那非和安慰剂在给药后12小时观察期间偏头痛发作发生率的差异。
结果：总计，16名参与者完成了这项研究。10名参与者（63％）在服用西地那非后12小时内经历了偏头痛发作，而安慰剂后3名（19％）（p=0.016）。西地那非后的中位头痛强度高于安慰剂后（12小时观察期的曲线下面积（AUC），p=0.026)。此外，西地那非诱导平均动脉血压显著降低(AUC，p=0.026）和同时增加心率（AUC，与安慰剂相比，p<0.001）。
结论：这些发现提供了证据，证明即使在CGRP受体阻断下，也可以通过cGMP途径诱导偏头痛。
背景：ClinicalTrials.gov：标识符NCT05889455。
