Association of acetazolamide infusion with headache and cranial artery dilation in healthy volunteers.

Abstract

The carbonic anhydrase inhibitor acetazolamide causes extracellular acidosis and dilatation of cerebral arterioles. In this study, we tested the hypothesis that acetazolamide also may induce headache and dilatation of cranial arteries. In a randomized double-blind crossover study design, 12 young healthy women were allocated to injection of 1 g acetazolamide or placebo on 2 separate days. We recorded headache on a verbal rating scale from 0 to 10 during an immediate phase (0-90 minutes) and a delayed phase (2-12 hours). The circumference of cranial arteries was measured using 3T high-resolution magnetic resonance angiography 30 and 60 minutes after injection. Acetazolamide provoked immediate headache in 9 participants compared to 3 participants after placebo (P=.031). Eleven participants reported headache in the delayed phase after acetazolamide, compared with 4 after placebo (P=.016). The area under the curve for headache was increased after acetazolamide compared to placebo in the delayed phase (2-12 h) (P=.005). Compared to placebo, arterial circumference increased after acetazolamide in the basilar artery (P=.002) as well as the cerebral (P=.003), cavernous (P=.002), and cervical (P=.005) parts of the internal carotid artery, but no other extracranial arteries changed after acetazolamide. In conclusion, acetazolamide caused immediate and delayed headache as well as dilatation of intracranial arteries in healthy volunteers. It is possible that extracellular acidosis induced by acetazolamide causes sensitization of cephalic perivascular nociceptors, which, in combination with vasodilatation, leads to delayed headache.

• Authors: Nanna Arngrim, Henrik Winther Schytz, Mohammad Sohail Asghar, Faisal Mohammad Amin, Anders Hougaard, Vibeke Andrée Larsen, Patrick J H de Koning, Henrik Bo Wiberg Larsson, Jes Olesen, Messoud Ashina
• Journal: Pain (Pain) Vol. 155 Issue 8 Pg. 1649-1658 (Aug 2014) ISSN: 1872-6623 [Electronic] United States
• PMID: 24861583 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Chemical References

• Carbonic Anhydrase Inhibitors
• Acetazolamide

Topics

• Acetazolamide (pharmacology)
• Adult
• Arteries (drug effects)
• Carbonic Anhydrase Inhibitors (pharmacology)
• Cerebrovascular Circulation (drug effects)
• Cross-Over Studies
• Double-Blind Method
• Female
• Headache (chemically induced)
• Healthy Volunteers
• Humans
• Vasodilation (drug effects)
• Young Adult