Discrepancy between strong cephalic arterial dilatation and mild headache caused by prostaglandin D₂ (PGD₂)

Introduction: Prostaglandins (PGs) are involved in nociception and mast cell degranulation. Prostaglandin D₂ (PGD₂) is a vasodilatator released during mast cell degranulation. The headache-eliciting effect of PGD₂ has not been studied in man. Subjects and methods: Twelve healthy volunteers were randomly allocated to receive intravenous infusion of 384 ng/kg/min PGD₂ over 25 min in a placebo-controlled, double-blind cross-over study. We recorded headache intensity and associated symptoms, velocity in the middle cerebral artery (V_MCA) and diameter of the superficial temporal artery (STA) and radial artery (RA) using ultrasonography. Results: In the period 0-14 h, 11 subjects reported headache on PGD₂ compared to one subject on placebo (P = 0.002). During the in-hospital phase (0-120 min), the area under the headache curve was larger on PGD₂ compared to placebo (P < 0.05). Median peak headache, 1 (0-1), occurred 10 min after start of PGD₂ infusion. There was no difference in incidence of headache in the post-hospital phase between PGD ₂ (n = 3) and placebo (n = 1). There was a decrease in V _MCA (P < 0.001), increase in STA (P < 0.001) and RA (P < 0.006) diameter during PGD₂ infusion compared to placebo. Peak decrease in V_MCA was 28.3% after 10 min and peak increase in STA was 55.7% after 20 min on the PGD₂ day. Conclusions: The present study shows that PGD₂ is a very strong vasodilator of MCA, STA and RA, but causes only mild headache.