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.

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.

Alternatively, hypersensitive or malfunctioning nerve cells in three nuclei in the brain stem might be the catalyst.

1. Parts of the brain stem, specifically the raphe nucleus, the locus coeruleus and the periaqueductal gray, behave abnormally.

2. The abnormal brain stem activity triggers spreading depression in the cortex or subcortex, thereby activating the trigeminal system.

3. In addition, the brain stem misbehavior can independently activate the pain pathways leading to the sensory cortex. 

Illustration Credit: Tami Tolpa