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

Treatments for migraine, both for prevention and for alleviation during an attack, have been problematic because they have not been tailored specifically to the disorder. Recent understanding of the neurobiology of migraine and the way the medicines work is leading to the development of more refined compounds with fewer side effects. Such compounds could intervene at various sites (marked on the diagram with Xs) and work in several ways.

The wave of hyperexcitability called cortical spreading depression involves ion transfer from glia (a class of brain cell) to neurons, through a form of ion channel called a gap junction. Gap junctions allow calcium to flow between glia and neurons, which activates the neurons. Compounds currently in clinical trials close these cellular pores to stop the wave in its tracks.

One of the ways that trigeminal nerves convey pain signals is by releasing the neurotransmitter calcitonin gene–related peptide (CGRP), which activates neurons in the trigeminal nucleus. A class of drugs called triptans alleviates migraine by blocking the release of CGRP. New treatments in advanced trials block the effects of CGRP.

Illustration Credit: Tami Tolpa (top); Jen Christiansen (bottom)