Pro-inflammatory and vasoconstricting prostanoid PGF2α causes no headache in man

Background: During two decades of migraine provocation studies with naturally occurring signalling molecules, vasodilators such as prostaglandin E-2, prostaglandin I-2 (prostacyclin) and prostaglandin D-2 were shown to be able to induce headache in man. To elucidate the role of inflammation and vasodilatation in the generation of headache, we investigated whether the pro-inflammatory and vasoconstricting prostanoid prostaglandin F-2 alpha (PGF(2 alpha)) would cause headache in a human model of headache. Methods: Twelve healthy volunteers were randomly allocated to receive 3.5 mu g/kg/min PGF(2 alpha) or placebo over 20 min in a two-way crossover study. We recorded headache intensity on a verbal rating scale, middle cerebral artery blood flow velocity (V-MCA) and the diameters of the superficial temporal artery (STA) and radial artery (RA). Results: We found no difference in the area under the curve (AUC) for immediate headache (0-90 min) between PGF(2 alpha) and placebo (p = 0.144). The McNemar's test showed no difference in the incidence of immediate and delayed headache between verum and placebo (p = 0.500 and p = 1.000, respectively). There was no difference in V-MCA (p = 0.776) and in the diameter of the STA (p = 0.460) or RA (p = 0.780) between PGF(2 alpha) and placebo. Conclusion: The present study shows that PGF(2 alpha), unlike vasodilating prostaglandins, does not provoke headache. We suggest that the vasodilating abilities of prostaglandins are important for the induction of experimental headache in healthy volunteers.