This story is a supplement to the feature "Why Migraines Strike" which was printed in the August 2008 issue of Scientific American.

Whether headache is initiated by the brain stem, by the cortex or by the subcortex remains an active debate.

SCENARIO 1: BLAME THE CORTEX
In this view, cortical spreading depression, caused by hypersensitive neurons in the cortex, induces both aura and pain. In patients without aura, a wave of neuronal hyperexcitability resembling cortical spreading depression might take place in subcortical regions.

1. Cortical spreading depression is triggered by neurons prone to hyperexcitability.

2. Those neurons release substances that activate trigeminal nerves, which send pain signals to the trigeminal nucleus in the brain stem.

3. The trigeminal nucleus conveys the signals to the thalamus, which relays them to the sensory cortex, involved in the sensation of pain.

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