Migraine Pain: Not Mainly In The Brain

April 21, 1999

Hopkins researchers think they've found the source of pain in migraines.

The research shifts explanations away from traditional ones involving dilating or constricting blood vessels to the back of the head and focuses instead on changes within the meninges, the protective tissue layers covering the brain.

The research, which involved SPECT scans of patients in the midst of a headache, points to a surer way to diagnose debatable migraines. It also offers scientists a straightforward method to judge therapy for the common headaches that plague millions nationwide. The study was presented at this week's American Academy of Neurology meetings in Toronto by Hopkins neurologist Marco Pappagallo, M.D., who headed a research team.

Patients in the study came to Hopkins in the midst of a well-documented migraine attack and pinpointed the site of their headache on a diagram. They then received IV injection of the common blood plasma protein, albumen, tagged with a radioactive isotope.

Radiologists took SPECT (single photon emission computerized tomography) scans of the head at 10 minutes and 3 hours, and then several days later, after headaches subsided, as a baseline. During inflammation that occurs during a migraine, Pappagallo says, blood vessels in the meninges become unusually permeable to molecules such as albumen. The SPECT scans then pick up the albumen leakage into surrounding tissues.

The images showed bright, diffuse patches -- a sign of inflammation -- at areas in the meninges that precisely matched places where patients said they felt their headaches, thus linking abnormalities in the meninges with the pain.

But the inflammation itself isn't the immediate cause of migraine pain, Pappagallo adds. That, the researchers believe, comes from abnormal nerve activity. Animal studies elsewhere show that electrically stimulating the trigeminal nerve, the major nerve leading from the brain to head and face, inflames the meninges.

Unlike inflammation sparked by trauma or infection, this "neurogenic inflammation" originates from chemicals -- neuropeptides -- released by nerve endings. "Neuropeptides trigger inflammation,"says Pappagallo, "but they also sensitize nearby pain receptors in the meninges which send the message of pain." The major drugs for migraines, ergot-based ones or sumatriptan, work because they block release of neuropeptides- a further bit of evidence, he says.

Traditional ideas on the origin of the pain looked at changes in blood flow to the head, particularly to the scalp. But Pappagallo has long suspected abnormalities in the meninges. "For one thing," he adds, "the symptoms of a bad migraine headache are the same as in meningitis, the bacterial or viral inflammation of the meninges: throbbing headache, nausea, and sensitivity to light and sound."

While the work is a very small pilot study, the SPECT images undeniably link the site of pain with the meninges, Pappagallo says. "There's no other way to explain something like this."

For all the research done on migraines, the disorder remains enigmatic. Scientists have only incomplete explanations for the overall cause. Traditional views hold that a somewhat epilepsy-like disturbance in a "trigger center" in the brainstem activates the trigeminal nerve which sends branches to the face, the scalp, to muscles surrounding blood vessels in the head and to the meninges. The other symptoms some people experience with migraines, such as numbness, tingling or visual disturbances, likely involve areas of the brain, rather than meninges, Pappagallo says.

The research was funded by Glaxo-Wellcome. Other researchers are Zsolt Szabo, Ph.D., Giuseppe Esposito, M.D., Anitha Lokesh and Lynette Velez.

Johns Hopkins Medicine

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