title: 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.affiliation: Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark Functional Imaging Unit, Diagnostic Department, Glostrup Hospital, Glostrup, Denmark Department of Radiology, Rigshospitalet, Copenhagen, Denmark Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Nanna
authors.initials: N
authors.lastname: Arngrim
authors.forename: Henrik Winther
authors.initials: HW
authors.lastname: Schytz
authors.forename: Mohammad Sohail
authors.initials: MS
authors.lastname: Asghar
authors.forename: Faisal Mohammad
authors.initials: FM
authors.lastname: Amin
authors.forename: Anders
authors.initials: A
authors.lastname: Hougaard
authors.forename: Vibeke Andrée
authors.initials: VA
authors.lastname: Larsen
authors.forename: Patrick J H
authors.initials: PJH
authors.lastname: de Koning
authors.forename: Henrik Bo Wiberg
authors.initials: HBW
authors.lastname: Larsson
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
authors.forename: Messoud
authors.initials: M
authors.lastname: Ashina
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000328:Adult; D001158:Arteries / Q000187:drug effects*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced*; D064368:Healthy Volunteers; D006801:Humans; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide
keywords: Acetazolamide; Cranial arteries; Extracellular acidosis; Headache; Magnetic resonance angiography; Migraine; Pain; Perivascular nociceptors; Sensitization; Vasodilatation