Recent advances in the elucidation of migraine pathophysiology

Abstract

Three hypotheses have been proposed so far regarding the pathophysiology of migraine: one is the "vascular theory", which posits cerebral vascular dysfunction as the etiological factor. The second is the "neuronal theory", which suggests that migraine is triggered by cortical spreading depression. The third is the "trigemino-vascular theory", which postulates that migraine is triggered by inflammation of trigeminal nerves and vessels around trigeminal ganglion cells. Nowadays, the "trigemino-vascular theory" is widely accepted. However, recent advances in imaging analysis indicate that the origin of migraine lies in a premonitory phase which precedes the aura phase. Modern imaging techniques such as functional MRI and PET reveal high activity of the hypothalamic area during the premonitory phase of migraine. These findings suggest that hypothalamic activation might be a generator of a migraine attack. On the other hand, current analyses show that the photosensitivity of migraine (photophobia) could be caused by dysfunction of the newly discovered intrinsically photosensitive retinal ganglion cells (ipRGCs). In the absence of visual signaling from rods and cones, light activation of ipRGCs expressing melanopsin photopigment is sufficient to produce photophobia during migraine. The ipRGCs project to the hypothalamus; their activation might be the trigger for migraine attacks. Significant advances in molecular biology and imaging in recent years have clarified the previous hypotheses of migraine pathophysiology.