Induction of cGMP-mediated migraine attacks is independent of CGRP receptor activation.

IF 5 2区医学 Q1 CLINICAL NEUROLOGY

Cephalalgia Pub Date : 2024-06-01 DOI:10.1177/03331024241259489

Bianca Raffaelli, Thien Phu Do, Håkan Ashina, Josefin Snellman, Tina Maio-Twofoot, Messoud Ashina

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引用次数: 0

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.

Conclusion: These findings provide evidence that migraine induction via the cGMP pathway can occur even under CGRP receptor blockade.

Trial registration: ClinicalTrials.gov: Identifier NCT05889455.

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诱导 cGMP 介导的偏头痛发作与 CGRP 受体激活无关。

背景：cAMP和cGMP途径与偏头痛发作的起因有关，但它们之间的相互作用仍不清楚。降钙素基因相关肽（CGRP）通过cAMP诱发偏头痛发作，而磷酸二酯酶-5抑制剂西地那非则通过cGMP诱发偏头痛发作。我们的目的是研究西地那非是否会诱发预先接受CGRP受体抗体艾伦单抗治疗的偏头痛患者发作偏头痛：在这项随机、双盲、安慰剂对照、交叉研究中，患有无先兆偏头痛的成人在第 1 天皮下注射 140 毫克艾伦单抗。然后在第8天和第21天之间的两个实验日随机接受西地那非100毫克或安慰剂，每个实验日至少间隔一周。主要终点是西地那非和安慰剂在用药后12小时观察期内偏头痛发作发生率的差异：共有 16 人完成了研究。10名参与者（63%）在服用西地那非后12小时内发作偏头痛，而服用安慰剂后只有3人（19%）发作偏头痛（p = 0.016）。服用西地那非后，头痛强度的中位数高于服用安慰剂后（12小时观察期内的曲线下面积（AUC），p = 0.026）。此外，西地那非还能显著降低平均动脉血压（AUC，p = 0.026），并同时增加心率（AUC，p 结论：西地那非能显著降低平均动脉血压（AUC，p = 0.026），并同时增加心率（AUC，p = 0.026）：这些发现提供了证据，表明即使在CGRP受体阻断的情况下，通过cGMP途径诱发偏头痛的情况也可能发生：试验注册：ClinicalTrials.gov：试验注册：ClinicalTrials.gov：Identifier NCT05889455。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cephalalgia 医学-临床神经学

CiteScore

10.10

自引率

6.10%

发文量

108

审稿时长

4-8 weeks

期刊介绍： Cephalalgia contains original peer reviewed papers on all aspects of headache. The journal provides an international forum for original research papers, review articles and short communications. Published monthly on behalf of the International Headache Society, Cephalalgia''s rapid review averages 5 ½ weeks from author submission to first decision.