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Sildenafil and calcitonin gene-related peptide dilate intradural arteries: A 3T MR angiography study in healthy volunteers

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  1. Exploration of purinergic receptors as potential anti-migraine targets using established pre-clinical migraine models

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  2. Sleep in cluster headache revisited: Results from a controlled actigraphic study

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  3. Calcitonin-gene related peptide and disease activity in cluster headache

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  4. Migraine is associated with high brain 5-HT levels as indexed by 5-HT4 receptor binding

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  1. Diagnostic yield of high-density versus low-density EEG: The effect of spatial sampling, timing and duration of recording

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  2. Electroconvulsive therapy increases cortical thickness in depression

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  3. Cortical thickness following electroconvulsive therapy in patients with depression - a longitudinal MRI study

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  4. Electroconvulsive therapy increases cortical thickness in depression

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Background Sildenafil and calcitonin gene-related peptide are vasoactive substances that induce migraine attacks in patients. The intradural arteries are thought to be involved, but these have never been examined in vivo. Sildenafil is the only migraine-inducing compound for which cephalic, extracranial artery dilation is not reported. Here, we investigate the effects of sildenafil and calcitonin gene-related peptide on the extracranial and intradural parts of the middle meningeal artery. Methods In a double-blind, randomized, three-way crossover, placebo-controlled head-to-head comparison study, MR-angiography was recorded in healthy volunteers at baseline and twice after study drug (sildenafil/ calcitonin gene-related peptide/saline) administration. Circumferences of extracranial and intradural middle meningeal artery segments were measured using semi-automated analysis software. The area under the curve for circumference change was compared using paired t-tests between study days. Results Twelve healthy volunteers completed the study. The area under the curveBaseline-120min was significantly larger on both the sildenafil and the calcitonin gene-related peptide day in the intradural middle meningeal artery (calcitonin gene-related peptide, p = 0.013; sildenafil, p = 0.027) and the extracranial middle meningeal artery (calcitonin gene-related peptide, p = 0.0003; sildenafil, p = 0.021), compared to placebo. Peak intradural middle meningeal artery dilation was 9.9% (95% CI [2.9-16.9]) after sildenafil (T30min) and 12.5% (95% CI [8.1-16.8]) after calcitonin gene-related peptide (T30min). Peak dilation of the extracranial middle meningeal artery after calcitonin gene-related peptide (T30min) was 15.7% (95% CI [11.2-20.1]) and 18.9% (95% CI [12.8-24.9]) after sildenafil (T120min). Conclusion An important novel finding is that both sildenafil and calcitonin gene-related peptide dilate intradural arteries, supporting the notion that all known pharmacological migraine triggers dilate cephalic vessels. We suggest that intradural artery dilation is associated with headache induced by calcitonin gene-related peptide and sildenafil.

Original languageEnglish
JournalCephalalgia
Volume39
Issue number2
Pages (from-to)264-273
Number of pages10
ISSN0333-1024
DOIs
Publication statusPublished - Feb 2019

    Research areas

  • human migraine models, middle meningeal artery, Neuroimaging

ID: 54888897