Pharmacologically Induced Headache Accompanied by Dilated Cephalic Vessels

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Sildenafil- and CGRP-induced headaches may be related to the dilation of the intradural middle meningeal artery.
Sildenafil- and CGRP-induced headaches may be related to the dilation of the intradural middle meningeal artery.

Headache induced by calcitonin gene-related peptide and sildenafil occurs with dilation of cephalic blood vessels, according to a study published in Cephalalgia. The dilation of intradural arteries may serve as pharmacological indicators of perivascular trigeminal activation in migraine.

This randomized, double-blind, head-to-head comparison study included 12 healthy volunteers whose MR-angiography was recorded at baseline and 2 times after administration of sildenafil, calcitonin gene-related peptide, or saline. The area under the curve for arterial circumference change was measured and compared between different study days. At baseline to 120 minutes, both sildenafil and calcitonin gene-related peptide showed a greater area under the curve in the extracranial middle meningeal artery (P=.021, sildenafil; P=.0003, calcitonin gene-related peptide) and intradural middle meningeal artery than placebo (P=.027, sildenafil; P=.013, calcitonin gene-related peptide). 

The maximum dilation of the intradural middle meningeal artery was 12.5% a half-hour after calcitonin gene-related peptide (95% CI, 8.1-16.8) and 9.9% a half-hour after sildenafil (95% CI, 2.9-16.9). Maximum dilation of extracranial middle meningeal artery 120 minutes after sildenafil was 18.9% (95% CI, 12.8-24.9) and 15.7% a half-hour after calcitonin gene-related peptide (95% CI, 11.2-20.1).

This three-way crossover study was placebo-controlled and included healthy individuals of both genders between the ages of 18 and 50. Patients were randomly assigned to oral sildenafil 100 mg, intravenous calcitonin gene-related peptide (20 minutes at 1.5 mg/min), or a placebo saline capsule. The study was performed on 3 days, with a mean of 23.5 days between study days.

The study researchers conclude that “[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.”

Multiple investigators declare affiliations with the pharmaceutical industry. Please refer to reference for a complete list of authors' disclosures.

Reference

Christensen CE, Amin FM, Younis S, et al. Sildenafil and calcitonin gene-related peptide dilate intradural arteries: A 3T MR angiography study in healthy volunteers [published online July 5, 2018]. Cephalalgia. doi: 10.1177/0333102418787336

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