Prostaglandin E2 induces immediate migraine-like attack in migraine patients without aura

Background: Prostaglandin E-2 (PGE(2)) has been suggested to play an important role in the pathogenesis of migraine. In the present experiment we investigated if an intravenous infusion of PGE(2) would induce migraine-like attacks in patients with migraine. Methods: Twelve patients with migraine without aura were randomly allocated to receive 0.4 mu g/kg/min PGE(2) (Prostin (R) E-2, dinoprostone) or placebo over 25 minutes in a two-way, crossover study. Headache intensity was recorded on a verbal rating scale, middle cerebral artery blood flow velocity (V-MCA) was measured by transcranial Doppler (TCD) and diameter of the superficial temporal artery (STA) was obtained by c-series scan (Dermascan C). Results: In total, nine migraine patients (75%) experienced migraine-like attacks after PGE(2) compared to none after placebo (p = 0.004). Seven out of 9 (58%) patients reported the migraine-like attacks during the immediate phase (0-90 min) (p = 0.016). Only two patients experienced the delayed migraine-like attacks several hours after the PGE(2) infusion stop (p = 0.500). The V-MCA decreased during the PGE(2) infusion (p = 0.005) but there was no significant dilatation of the STA (p = 0.850). Conclusion: The migraine-like attacks during, and immediately after, the PGE(2) infusion contrast with those found in previous provocation studies, in which the other pharmacological compounds triggered the delayed migraine-like attacks several hours after the infusion. We suggest that PGE(2) may be one of the important final products involved in the generation of migraine attacks.