BOSTON—In patients with migraine, activity in a central pain modulation center may be aberrant even between attacks, according to David Borsook, MD, PhD, and colleagues. The finding sheds light on how migraine affects the brain and may provide a biomarker for investigating new therapies, the researchers reported at the 50th Annual Scientific Meeting of the American Headache Society.
Previous studies have found changes in the brain during migraine attacks, Dr. Borsook said, but little is known about migraine-related functional changes in the brain during the interictal period. To explore those changes, the researchers compared the brain activity of 12 patients with migraine with that of 12 healthy controls, using fMRI to determine brain regions where activity changed in response to warmth or noxious heat. At the time of the study, the patients had been free of migraine for at least seven days.
Compared with controls, patients with migraine had highly significant hypoactivity in the nucleus cuneiformis (NCF), the investigators found. These differences were not correlated with any clinically apparent hypersensitivity to pain.
“One can’t differentiate these patients clinically,” said Dr. Borsook, who is an Associate Professor of Psychiatry at the Harvard Medical School in Boston. “This is an example of the power of fMRI to detect changes in processing of neural signals” that cannot be found otherwise.
The involvement of the NCF is significant, because it is known as part of a descending processing pathway for pain signals, noted Dr. Borsook. “Our interpretation of the findings is that the NCF is inherently dysfunctional, perhaps hypofunctional, in migraineurs,” he said, “and thus is less effective in filtering out pain signals from reaching higher brain areas.”
The cause of the changes in the NCF is unknown, but Dr. Borsook speculated that they may be the result of long-term stimulation from central trigeminovascular neurons, from which the NCF receives direct input. It is possible, he said, that over time the NCF loses its ability to turn down pain messages it is receiving, exacerbating migraine and leading into a vicious circle, possibly setting the stage for transition from acute intermittent to chronic migraine. More work will be needed to test this hypothesis, Dr. Borsook asserted.
The potential therapeutic implications of these findings could be “quite large,” Dr. Borsook said, if interictal hypoactivity proves to be a reliable biomarker. “This could open a number of doors,” including using changes in the signal for investigating migraine prophylactic drugs.