RETINAL PLASMA EXTRAVASATION IN ANIMALS BUT NOT IN HUMANS - IMPLICATIONS FOR THE PATHOPHYSIOLOGY OF MIGRAINE

High-intensity electrical stimulation of the trigeminal ganglion is ac companied by mast cell degranulation, vasodilatation, increased endoth elial permeability and leakage of albumin from postcapillary venules w ithin the dura mater. Overall, the histological appearance suggests an evolving sterile inflammatory response. This neurogenic inflammation within the meninges has been suggested as a model to explain the pain in migraine and cluster headache, and has been used to characterize th e pharmacology of anti-migraine compounds. Using the rat model of neur ogenic inflammation, the albumin extravasation ratio (stimulated : uns timulated side) in vehicle-treated animals in the dura and retina was 1.60 +/- 0.11 and 1.76 +/- 0.18, respectively (n = 10; values are mean +/- SEM). Pretreatment with sumatriptan (n = 9) produced a highly sig nificant reduction in the ratio of extravasation within the dura to 1. 10 +/- 0.06 (P = 0.002) and in the retina to 0.96 +/- 0.06 (P +/- 0.00 1), as did the neurokinin-l receptor antagonist RP 67580 (Iz = 12) in the dura (1.04 +/- 0.11, P = 0,002) and retina (1.08 +/- 0,06, P = 0,0 01), These data demonstrate increased endothelial permeability and lea kage of albumin not only in the dura but also in the retina. In a seco nd stage we investigated possible extravasation in the human retina in acute migraine (n = 8) and cluster headache (Iz = 5) using fluorescei n or indocyanine angiography, No increased endothelial permeability or leakage of dye could be found in the human retinal or choroidal vesse ls during headache attacks or in the headache-free interval in persons suffering from both migraine and cluster headache. These data raise t he possibility that neurogenic inflammation is not a major factor in h eadache attacks in migraine or cluster headache.