Prostaglandins in migraine: update.
This review presents recent findings on the role of prostaglandins in migraine pathophysiology. Experimental studies have shown that prostaglandins are distributed in the trigeminal-vascular system and its receptors are localized in the trigeminal ganglion and the trigeminal nucleus caudalis. Prostaglandins were found in smooth muscles of cranial arteries, and functional studies in vivo showed that prostaglandins induced dilatation of cranial vessels. Human studies showed that intravenous infusion of vasodilating prostaglandins such as prostaglandin E₂ (PGE₂), prostaglandin I₂ (PGI₂) and prostaglandin D₂ (PGD₂) induced headache and dilatation of intra-cranial and extra-cranial arteries in healthy volunteers. In contrast, infusion of non-dilating prostaglandin F₂α (PGF₂α) caused no headache or any vascular responses in cranial arteries. PGE₂ and PGI₂ triggered migraine-like attacks in migraine patients without aura, accompanied by dilatation of the intra-cerebral and extra-cerebral arteries. A novel EP4 receptor antagonist could not prevent PGE₂-induced headache in healthy volunteers. Recent in-vitro/in-vivo data demonstrated presence and action of prostaglandins within the trigeminal pain pathways. Migraine induction after intravenous administration of PGE₂ and PGI₂ suggests a specific blockade of their receptors, EP and IP respectively, as a new potential drug target for the acute treatment of migraine.