A9 Migraine (spread cortical depression)

Topic

The cerebral cortex normally maintains a stable concentration of potassium in the extracellular space surrounding its neurons. In migraine with aura, something disrupts this balance: the cerebral cortex releases potassium into the extracellular space, and this extracellular potassium diffuses across the cortex. When the extracellular potassium concentration exceeds a local threshold within the cerebral cortex, a wave of depolarization is triggered and propagates slowly across the cortex; the migraine aura is associated with this cortical depolarization wave.

The speed at which this depolarization wave advances across the cerebral cortex depends on two factors: the higher the diffusivity of extracellular potassium, the faster the wave advances; likewise, the higher the rate of extracellular potassium release, the faster the wave advances. This type of propagation—governed by the release and diffusion of a substance within the cerebral cortex—is analogous to that previously used to describe the propagation of electrical discharge in another model of the nervous system.

As the depolarization wave passes, the cerebral cortex also undergoes a change in blood flow: a phase of hypoperfusion occurs first, during which blood flow to the cortex decreases; this is followed by a phase of hyperemia, during which blood flow to the cortex increases above normal levels. This follows the same blood flow dynamics previously used to describe the blood supply to the cerebral cortex in another model.

Furthermore, the passage of the depolarization wave across the cerebral cortex activates the trigeminovascular system, which releases a specific vasoactive peptide in response to this activation. This specific vasoactive peptide is directly responsible for two effects: on the one hand, it causes vasodilation of the meninges surrounding the cerebral cortex, and on the other, it promotes the progressive sensitization of central pain pathways.

This progressive sensitization of central pain pathways—triggered by the vasoactive peptide released by the trigeminovascular system following the passage of the depolarization wave across the cerebral cortex—transforms the migraine aura episode into the characteristic migraine headache; it is also the same mechanism that, more broadly, is revisited later to describe chronic neuropathic pain. Overall, it is the abnormal activity of the cerebral cortex—ranging from the initial release of extracellular potassium to the sensitization of pain pathways—that accounts for both the aura and the pain of the migraine.

ID:4291