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