The New York Times - April 7, 2009
Benedict Carey

Perhaps neither one, a new study suggests. Neuroscientists at the University of Minnesota report that specialized cells in the spinal cord appear to be critically involved in producing the sensation of itch and the feeling of relief after the application of fingernails, at least in healthy individuals. The study appears in the current issue of the journal Nature Neuroscience.

"It's as if there's a little brain in there that creates this state in which scratching -- which normally excites pain cells -- instead inhibits them," said Glenn J. Giesler, a co-author of the study. The same cells that register the itch also are sensitive to pain.

"It's a very important study; itching is a major problem for millions of patients," said Dr. Gil Yosipovitch, a dermatologist at the Wake Forest University School of Medicine and founder of the International Forum for the Study of Itch.

Dr. Yosipovitch cautioned that the findings may not apply to the sort of chronic itch that plagues people with atopic eczema, H.I.V. or chronic kidney problems. "But this is the kind of work that should help open this area up to more research."

In the study, led a postdoctoral student, Steve Davidson, researchers isolated in monkeys cellular connections that run from the surface of the foot to the spinal cord and then to the thalamus, a clearinghouse for sensations in the brain, down through the spinal cord to the surface of the foot. They induced the sensation by injecting histamines under the skin.

The scientists took single-cell recordings in an area at the base of the spinal cord, in the lower back, in so-called spinothalamic neurons. These cells are sprinkled throughout the spinal cord. Most are sensitive to pain, and some to both pain and itch. The cells apparently detected the injection and began firing immediately afterward. And when the researchers scratched the itchy skin on the monkeys' feet, it quieted the cells' activity.

"It's the first time I've ever seen a noxious stimulus -- the scratching -- stop the firing of cells," Dr. Giesler said. His co-authors, along with Mr. Davidson, were Xijing Zhang, Sergey G. Khasabov and Donald A. Simone.

Scientists argue that itching is most likely related to grooming, and evolved to protect animals against some toxic plants, as well as insects, along with the diseases they can transmit, like malaria, yellow fever and river blindness. But the biology of itch has been a mystery, and neglected for years by researchers, who have been far more focused on pain.

Some 50 diseases leave people in a misery of itching which usually cannot be treated. Studies among kidney disease patients and psychiatric inpatients have found that itch is among the top complaints. And when it is severe it keeps people up at night, often worsening their condition.

The new study suggests that itch, like pain, may be a "gated" system in which signals from other nerve cells can interfere with or moderate the sensation. Scratching the skin near, but not directly on, the spot that itches often provides relief, just as rubbing an aching limb can reduce pain. Perceptions in the brain, too, probably moderate the urge to scratch: some chronic, compulsive cases of itching suggest that the brain is not properly reading the effect of outside signals at all but is instead acting on a mistaken internal representation of what is happening to the skin.

As with some kinds of pain, subtle reminders of an itching sensation can get people scratching, often without being entirely aware of it.

"I give lectures about itching," Dr. Giesler said, "and I'll stand up there in front of a whole roomful of people, show a few slides and pretty soon I'll look out and 90 percent of the audience is scratching."

Like yawning, itching also seems to be contagious, which suggests a significant top-down influence from the brain.

Dr. Yosipovitch said there was a long way to go before doctors could expect treatments. For one thing, the miserable, chronic itch common in many medical problems most likely involves other mechanisms in addition to those identified in the study. And the brain may be critically involved in escalating itch, in ways that are not yet understood. "But as a clinician, I feel excited about the finding," he said. "It's a sign that this field is really evolving."
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