Mast Cell Degranulation Mediates Compound 48/80-İnduced Meningeal Vasodilatation Underlying Migraine Pain

Objective: The cranial dura mater contains plenty of mast cells and is principally supplied by the middle meningeal artery which has a key role in the generation of headaches. Neurogenic inflammation caused by perivascular nerve activation and dural vasodilation is held responsible for migraine pain. Dural mast cells contribute neurogenic inflammation and migraine via vasoactive and proinflammatory mediators in their secretory granules. In the present study, it was aimed to investigate vasoactive effect of mast cell degranulating agent compound 48/80 induced dural mast cell degranulation on the middle meningeal artery and its anterior and posterior branches. Methods: Isolated skulls obtained from male Wistar rats were divided into 2 halves. The skull cavities with intact the dura mater were applied synthetic interstitial fluid for control group or mast cell degranulating agent compound 48/80 (10 μg/ml) in synthetic interstitial fluid for treated group at 37 o C for 15 min. Diameters of middle meningeal artery and its anterior and posterior branches were measured and mast cells were counted from whole-mount preparations of meningeal dura mater. Results: While compound 48/80 induced massive degranulation of dural mast cells (P<0.01), it did not change the number of mast cells in the dura mater. Moreover, compound 48/80 increased diameter of middle meningeal artery (P<0.01) and its anterior (P<0.05) and posterior (P<0.01) branches, respectively compared to synthetic interstitial fluid treatment. Conclusion: Dural mast cell degranulation causes dilatation of middle meningeal artery which is involved in the pathophysiology of migraine, therefore testing of mast cell stabilizing agents in vivo models of migraine pain may promise hope for the next big things in the treatment of migraine headaches.