Peripheral Projections of the Trigeminovascular System as Antimigraine Target

Background: The exact mechanisms underlying the onset of a migraine attack are not completely understood. It is, however, now well accepted that the onset of the excruciating headache of migraine is mediated by the activation and increased mechanosensitivity (i.e. sensitization) of trigeminal nociceptive afferents that innervate the cranial meninges and their related large blood vessels.
Objective: To provide a critical summary of current understanding of the role that the cranial meninges, their associated vasculature, and immune cells play in meningeal nociception and the ensuing migraine headache.
Methods: We discuss the anatomy of the cranial meninges, their associated vasculature, innervation and immune cell population. We then debate the meningeal neurogenic inflammation hypothesis of migraine and its putative contribution to migraine pain. Finally, we provide insights into potential sources of meningeal inflammation and nociception beyond neurogenic inflammation and their potential contribution to migraine headache.