The painfully sensitive skin that accompanies many migraines has revealed a new understanding of the debilitating headaches. The latest findings from Boston researchers are the first that may explain why current medications are ineffective in many cases and suggest a new target for the next generation of migraine drugs.
Researchers from Beth Israel Deaconess Medical Center documented extreme skin sensitivity in 79 percent of migraine sufferers who were tested several hours after their headache pain began. The other 21 percent of people with migraines showed no increase in skin sensitivity. The study of 42 people is published in the May issue of the Annals of Neurology.
“Patients tell us they can’t brush their hair, wear earrings or eyeglasses, or shave their beards because it’s so painful,” says first author Rami Burstein, a pain researcher in the Beth Israel Deaconess anesthesiology department. “The immediate implication of this finding, and the understanding of the neuronal mechanism behind it, is that patients need to treat their migraines as soon as the pain starts.” Burstein is also an associate professor at Harvard Medical School.
Migraines affect an estimated 25 million Americans, mostly women. There is no known cure for migraine disease, only treatments for the symptoms, and the treatments are ineffective in many cases. In addition to the throbbing pain in the head or around the eyes, migraine symptoms can include flashing lights, zigzag lines, or temporary vision loss; speech difficulty; tingling of the face or hands; and nausea. Although hypersensitive skin may not come as a surprise to some patients and experienced doctors, this is believed to be the first time these symptoms have been documented in rigorous testing.
“This is the most important paper on headache in a long time,” says Stephen Silberstein, professor of neurology at Thomas Jefferson University in Philadephia. “It’s a logical approach to the problem of headaches, beginning with a laboratory model, validating it in the clinic and suggesting therapeutic options.”
Researchers Surprised by Findings
The study verifies in humans for the first time a migraine model proposed by Burstein and his colleagues four years ago. Experimental headaches in rats had suggested the underlying mechanism of the throbbing, pounding sensation of migraines. Pain signals from blood vessels inside the head made the nerves hypersensitive, converting routine blood pulsing into throbbing pain during a migraine.
Further animal studies also predicted increased skin sensitivity in people, especially around the eyes on the side of the head where the migraine occurs. The same pain signals that sensitize the nerve also sensitize spinal cord neurons at the base of the skull. There, where other nerves connect, the sensitized neurons distort normal sensory signals from skin around the eyes and send a message of pain up to the brain.
In the latest study, researchers were surprised to find that some people reported skin sensitivity on their faces or heads, not just around their eyes, and 42 percent with hypersensitive skin reported sensitivity all over their bodies.
It’s possible that hypersensitive neurons in the spinal cord at the base of the skull may sensitize yet another set of neurons, the ones in the thalamus region of the brain. This may explain why tight clothes, jewelry, a shower, and even the weight of a blanket become painful and irritating. In turn, the thalamus may misinterpret normal signals from other parts of the body as painful.
Burstein and his colleagues will test this idea.
“This study breaks new ground in this field,” says Michael Moskowitz, professor of neurology at Harvard Medical School and Massachusetts General Hospital. “It provides the first explanation of certain migraine symptoms not previously understood.”
Lessons for Doctors, Patients
Currently approved migraine medications act on the blood vessels and pain fibers that carry the initial pain signals, not at the level of the spinal cord where the sensitization is taking place, Burstein says. For people with skin sensitivity, the study suggests that current migraine medications are most effective if taken immediately at the onset of a migraine attack. Then, they can prevent the distorted signals from being sent to the brain. Unfortunately, the cost of medications, the uncertainty of early migraine warning signs, and the onset of migraines during sleep may discourage effective use of current medications for some people.
The study suggests a target for a new generation of migraine drugs that would prevent hypersensitivity of the spinal cord neurons at the base of the skull. Burstein and his colleagues continue to work on understanding the molecular basis of changes in the properties of the neurons in hopes of eventually preventing changes or reversing the sensitization.