Prostaglandin I2 (epoprostenol) triggers migraine-like attacks in migraineurs.
Prostacyclin [prostaglandin I(2) (PGI(2))] activates and sensitizes meningeal sensory afferents. In healthy subjects PGI(2) triggers headache in healthy subjects. However, the migraine-eliciting effect of PGI(2) has not been systematically studied in patients with migraine. We hypothesized that intravenous infusion of the stable prostacyclin analogue epoprostenol would trigger migraine-like attacks in migraineurs. We infused 10 ng kg(-1) min(-1) PGI(2) or placebo over 25 min in 12 migraineurs without aura in a controlled, double-blind, cross-over study and recorded headache intensity and associated symptoms, velocity in the middle cerebral artery (V(MCA)) and diameter in the superficial temporal artery. In the period 0-14 h, 12 subjects reported headache on PGI(2) day compared with three subjects on placebo day (P = 0.004), and six subjects fulfilled the criteria for an experimentally induced migraine-like attack compared with two subjects on placebo (P = 0.219). During infusion and post-infusion phases the AUC under the headache curve on PGI(2) was significantly larger than on placebo (P < 0.05). There was a significant V(MCA) decrease (P = 0.015) and superficial temporal artery diameter increase (P < 0.001) on PGI(2) compared with placebo. In conclusion, PGI(2) may trigger a migraine-like attack in migraine sufferers. We suggest sensitization of perivascular nociceptors and arterial dilation as the mode of action of PGI(2)-induced headache and migraine-like attacks.
Wienecke
T
T
Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Danish Headache Centre, Glostrup, Copenhagen, Denmark.
Olesen
J
J
Ashina
M
M
D000328:Adult; D019540:Area Under Curve; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D011464:Epoprostenol / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects; D008881:Migraine Disorders / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D012372:ROC Curve; D013699:Temporal Arteries / Q000187:drug effects
D011464:Epoprostenol