Migraine is a class of recurrent headache sometimes preceded by an "aura." The aura typically involves visual changes -- seeing lines, spots, or even hallucinations.
Auras have consistently been tied to "cortical spreading depression," during which a wave of decreased brain cell activity crosses the cortex, the outermost part of the brain. This presumed connection contributed to the theory that cortical depression could spark the aura and, subsequently, the pain of migraine.
But a number of clinical and experimental observations conflict with this theory, especially the evidence that only one in five migraine patients experiences an aura preceding the pain and other symptoms (e.g., difficulty with speech or movement, tingling sensations, or vertigo).
This makes the dominant contemporary theory seeking to explain migraine headaches unlikely to be correct, say the researchers of a report published in the January 2001 issue of Annals of Neurology, the scientific journal of the American Neurological Association.
The German researchers, working in an animal model, failed to find a link between the wave of brain activity known as cortical spreading depression, postulated to underlie migraine symptoms, and various markers of the inflammation that accompanies migraine headache pain.
"We suspect that a still-unidentified stimulus causes spreading depression on the one hand and headache pain on the other," said senior author Frank Richter, Ph.D., a researcher at the University of Jena in Germany.
Dr. Richter and his colleagues decided to test the theory by triggering spreading depression in the cortex of rats and then probing for activity in the nervous system and blood circulation that would reflect the instigation of migraine headache.
What they discovered cast even further doubt on the presently accepted theory.
The researchers found no change in the activity of nerve centers that should have been the "output station" if spreading depression causes an inflammation in the dura mater, a membrane that covers the brain.
The dura mater becomes inflamed during migraine in humans.
The researchers also failed to detect evidence of spreading depression-induced dura mater inflammation; in particular, they found no increases in the chemicals calcitonin gene-related peptide (CGRP) and prostaglandin E-2, which typically increase in concentration during migraine headaches.
"Absence of CGRP release is a pivotal negative finding, because it is a reliable finding in migraine patients during headache that can link human and experimental studies," wrote Peter J. Goadsby, MD, PhD, of the National Hospital Institute of Neurology in London, in an accompanying editorial.
Richter and his colleagues believe that the best explanation for the observed anomaly is that cortical spreading depression is a process parallel to, but detached from, the phenomenon that causes the pain of migraine. The researchers emphasize that further research must be conducted before changes in the conventional treatment for migraine headaches can occur.
"Our data will not influence current migraine therapy," says Richter. Instead, the researchers will now focus on finding the common source of the pain processes in the dura and the spreading depression and aura.