Meningeal mast cells, inflammation and migraine pain

Migraine is a debilitating, throbbing headache that afflicts about 15% of the Western population. While the underlying cause of migraine is still a matter of speculation, the intracranial throbbing pain of migraine is largely attributed to an episode of local sterile meningeal inflammation that promote activation of trigeminal mechanosensitive nociceptive afferents that supply the meninges. The key players responsible for triggering such nociceptive neuronal events remain poorly defined, however. Mast cells, resident inflammatory cells that populate the meninges, particularly the dura mater, were implicated in the pathophysiology of migraine more than 50 years ago. Additional clinical and preclinical data that further support their role in migraine have recently emerged. This review highlights these findings, examines the evidence of a neuroimmune interaction between meningeal nociceptors and mast cells, in particular their involvement in promoting the activation and sensitization of the trigeminovascular systems, and will finally discuss the notion that in some migraine attacks, mast cells serve as an intermediate between various migraine triggers and the persistent activation of meningeal nociceptors.