Prostaglandin I2 (epoprostenol) triggers migraine-like attacks in migraineurs

Abstract

Prostacyclin [prostaglandin I2 (PGI2)] activates and sensitizes meningeal sensory afferents. In healthy subjects PGI2 triggers headache in healthy subjects. However, the migraine-eliciting effect of PGI2 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 PGI2 or placebo over 25 min in 12 migraineurs without aura in a controlled, double-blind, cross-over study and recorded headache intensity and associated symptons, velocity in the middle cerebral artery (VMCA) and diameter in the superficial temporal artery. In the period 0–14 h, 12 subjects reported headache on PGI2 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 PGI2 was significantly larger than on placebo ( P < 0.05). There was a significant VMCA decrease ( P = 0.015) and superficial temporal artery diameter increase ( P < 0.001) on PGI2 compared with placebo. In conclusion, PGI2 may trigger a migraine-like attack in migraine sufferers. We suggest sensitization of perivascular nociceptors and arterial dilation as the mode of action of PGI2-induced headache and migraine-like attacks.