Migraine pain, meningeal inflammation, and mast cells

Migraine pain has been attributed to an episode of local sterile meningeal inflammation and the subsequent activation of trigeminal primary afferent nociceptive neurons that supply the intracranial meninges and their related large blood vessels. However, the origin of this inflammatory insult and the endogenous factors that contribute to the activation of meningeal nociceptors remain largely speculative. A particular class of inflammatory cells residing within the intracranial milieu, known as meningeal mast cells, was suggested to play a role in migraine pathophysiology more than five decades ago, but until recently the exact nature of their involvement remained largely unexplored. This review examines the evidence linking meningeal mast cells to migraine and highlights current experimental data implicating these immune cells as potent modulators of meningeal nociceptors' activity and the genesis of migraine pain.