Cephalalgia
Volume 29 Issue 12, Pages 1294 - 1300
Published Online: 11 May 2009
© 2008 International Headache Society
D Daugaard, LL Thomsen, HK Iversen & J Olesen
Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Copenhagen, Denmark
Correspondence to Jes Olesen MD, PhD, Department of Neurology, Glostrup Hospital, Nordre Ringvej, Glostrup, 2600 Denmark. Tel. + 45-4323-3036, e-mail jeol@glo.regionh.dk
ABSTRACT
Glyceryl trinitrate (GTN) is a pro-drug dissociating nitric oxide throughout the body. It dilates cephalic arteries without increasing cerebral blood flow (CBF). GTN induces headache in healthy volunteers and migraine attacks in migraineurs. Acetazolamide (Az) increases CBF but does not dilate cerebral arteries. The hypothesis tested here was that Az, by dilating cerebral arterioles but not arteries and thereby decreasing pulsatile stretching of the wall of the large arteries and their perivascular sensory nerves, would reduce or prevent the GTN-induced headache We tested this hypothesis in 14 healthy volunteers. In a randomized, double-blind, cross-over study, they were pretreated with Az or placebo followed on both study days by a GTN infusion of 0.5 µg kg−1 min−1 for 20 min. Headache was scored on a verbal rating scale and a headache diary was kept for 12 h. Mean blood velocity of the middle cerebral artery was measured (transcranial Doppler). Our hypothesis was disproved, as Az did not decrease GTN-induced headache. Unexpectedly but interestingly, GTN combined with Az induced more delayed headache than GTN alone. Furthermore, a migraine-like headache was observed in three volunteers, who did not develop migraine after GTN alone. The fact that a suitable pharmacological intervention may trigger migraine in individuals with no prior migraine may suggest that the ability to develop migraine without aura is a quantitative genetic trait.
Received 18 December 2008, accepted 15 February 2009
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