23 April 1999
Migraine pain - It's all in your head
A research team from John Hopkins University believes they have located the source of pain in migraines, or at least are much closer to finding it. This shifts the research focus away from explanations that involve dilating or constricting blood vessels to the back of the head. Instead the findings point to changes in the meninges, the protective tissue layers covering the brain, as the cause of such pain.
The research greatly assists a confident diagnosis of the condition, the validity or even existence of which some people have questioned, even though many millions of people around the world suffer from the condition. Establishing appropriate and effective treatment will also be greatly furthered. The study was presented at this week's American Academy of Neurology meetings in Toronto by Hopkins neurologist Marco Pappagallo, M.D., who headed the research team.
Patients in the study came to Hopkins in the midst of a migraine attack and located the exact site of their headache on a diagram. They then received an injection of the common blood plasma protein, albumen, that contained 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 - an indication of inflammation - at areas in the meninges that precisely matched places where patients said they felt their headaches, linking abnormalities in the meninges with the pain. This explains why migraine sufferers demonstrate similar symptoms to diseases that affect the meninges. "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" says Pappagallo.
However, this inflammation is a symptom not the cause of pain. Rather, pain is caused from abnormal nerve activity. And animal studies have shown 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.
However, while much research has been done on disorder, the exact cause remains unclear. Established views contend that a 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.