Peripheral and central sensitization during migraine.

Abstract

Current theories propose that the pain of migraine is caused by chemical activation of meningeal perivascular fibers. In an animal model of migraine, we have recently shown that chemical activation of meningeal primary afferent nociceptors that innervate the dura could lead to the following: a) peripheral sensitization of these nociceptors to intracranial mechanical stimulation; b) central sensitization of second-order trigeminovascular neurons that receive convergent input from the dura and skin to extracranial mechanical and thermal stimulation; and c) facilitated cardiovascular pressor responses that are usually indicative of pain. These findings provide the first set of evidence for the induction of peripheral and central sensitization along trigeminovascular pain pathways by visceral input from the intracranial dura. We propose that the throbbing pain of migraine is mediated mainly through peripheral and to a lesser extent through central sensitization, and that the development of scalp tenderness is mediated mainly through central sensitization.