The neurobiology of migraine

Abstract

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.

Copyright © 2011 Elsevier B.V. All rights reserved.

Figures

Fig. 7.1

Cortical spreading depression (CSD) and astrocyte calcium waves. (A) Optical imaging of the cortical surface in a mouse. Far left panel shows image of mouse cortex visualized through the thinned skull of an anesthetized mouse (a recording electrode is seen in the upper right of the field; image scale = 1200 × 1200 μm). Subsequent images show change in reflectance of this area of cortex over time associated with a CSD wave. A change in optical signal of the parenchyma spreads slowly across the cortex. Dilation (darkening) of surface arteries propagates ahead of the CSD wavefront, followed by constriction of these vessels accompanying the CSD wave. (B) Astrocyte calcium wave. Images show fluorescence of the calcium indicator fluo-4 with an inverse gray scale (darker gray indicates higher intracellular calcium; image scale = 400 × 400 μm). Mechanical stimulation of a single cell with a micropipette evokes a wave of increased calcium concentration that spreads from cell to cell over as many as hundreds of cells. The temporal and spatial characteristics of this wave are remarkably similar to those of CSD.

Fig. 7.2

Schematic of hypothesized sequence of events in migraine. Each step in the sequence may have discrete thresholds, and involve distinct molecular, cellular, and neurochemical pathways. This complexity may underlie the heterogeneous and variable clinical presentation of migraine. BBB, blood–brain barrier.