Prostaglandin E₂ (PGE₂) induces headache in healthy subjects

The role of prostanoids in nociception is well established. The headache-eliciting effects of prostaglandin E₂ (PGE₂) and its possible mechanisms have previously not been systematically studied in man. We hypothesized that infusion of PGE₂ might induce headache and vasodilation of cranial vessels. PGE₂ (0.40 μg kg^-1 min^-1) or saline was infused for 25 min into 11 healthy subjects in a cross-over, double-blind study. Headache intensity was scored on a verbal rating scale from 0 to 10. In addition, we recorded mean flow in the middle cerebral artery (V_MCA) by transcranial Doppler and diameter of the superficial temporal artery (STA) by high-resolution ultrasonography. All 11 subjects reported headache on the PGE₂ day and no subjects reported headache on the placebo day (P = 0.001). During the immediate phase (0-30 min) (P = 0.005) and the postinfusion phase (30-90 min) (P = 0.005), the area under the curve for headache score was significantly larger on the PGE₂ day compared with the placebo day. PGE₂ caused dilatation of the STA (23.5%; 95% CI 14.0, 37.8) and the MCA (8.3%; 95% CI 4.0, 12.6). We suggest that PGE₂ induces headache by activation and sensitization of cranial perivascular sensory afferents.