The neurobiology of migraine.

The understanding of migraine has moved well beyond its traditional characterization as a "vascular headache." In considering the basic neurobiology of migraine, it is important to begin with the concept of migraine as not merely a headache, but rather a heterogeneous array of episodic symptoms. Among the array of phenomena experienced by migraine patients are visual disturbances, nausea, cognitive dysfunction, fatigue, and sensitivity to light, sound, smell, and touch. These symptoms may occur independently or in any combination, and in some patients occur even in the absence of headache. The diversity and variability of symptoms experienced by migraine patients belies a complex neurobiology, involving multiple cellular, neurochemical, and neurophysiological processes occurring at multiple neuroanatomical sites. Migraine is a multifaceted neurobiological phenomenon that involves activation of diverse neurochemical and cellular signaling pathways in multiple regions of the brain. Propagated waves of cellular activity in the cortex, possibly involving distinct glial and vascular signaling mechanisms, can occur along with activation of brainstem centers and nociceptive pathways. Whether different brain regions become involved in a linear sequence, or as parallel processes, is uncertain. The modulation of brain signaling by genetic factors, and by sex and sex hormones, provides important clues regarding the fundamental mechanisms by which migraine is initiated and sustained. Each of these mechanisms may represent distinct therapeutic targets for this complex and commonly disabling disorder.