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Under the skin

Science is now not just scratching the surface to understand why we itch

By: New York Times | Published: February 23, 2014 12:58:30 am

The experiment was not for the squirmish. Volunteers were made to itch like crazy on one arm, but not allowed to scratch. Then they were whisked into an MRI scanner to see what parts of their brains lit up when they itched, when researchers scratched them and when they were allowed to scratch themselves. The scientific question was this: Why does it feel so good to scratch an itch?

“It’s quite intriguing to see how many brain centres are activated,” said Dr Gil Yosipovitch, chairman of dermatology at the Temple University School of Medicine and director of the Temple Center for Itch. “There is no one itch centre. Everyone wants that target, but it doesn’t work in real life like that.”

Instead, itching and scratching engage brain areas involved not only in sensation, but also in mental processes that help explain why we love to scratch: motivation and reward, pleasure, craving and even addiction. What an itch turns on, a scratch turns off — and scratching oneself does it better than being scratched by someone else. The study results were published in the journal PLOS One.

Itching was long overshadowed by pain in both research and treatment, and was considered just a mild form of pain. But millions of people suffer from itching, and times have changed. Research has found nerves, molecules and cellular receptors that are specific for itching and set it apart from pain, and the medical profession has begun to take it seriously as a debilitating problem.

Within the last decade, there has been a flurry of research into what causes itching and how to stop it. Along with brain imaging, studies have begun to look at gene activity and to map the signals that flow between cells in the skin, the immune system, the spinal cord and the brain.

The concern is not so much the fleeting nastiness of mosquito bites and poison ivy, but the misery caused by chronic itching and that often resists remedies.

For the first time in the US, itching research and treatment centres have opened. “Itch is now where pain was probably 20 years ago,” said Dr Lynn Cornelius, chief of the dermatology division at Washington University School of Medicine. “The science has to lead to treatment, I believe. Clinicians won’t just look upon someone itching as someone who needs antihistamines.”

Itching appears widespread in the animal kingdom —  though no one knows for sure why animals claw, bite or peck themselves, or scrape against trees or fences. Even fruit flies engage in “robust grooming behaviours” that look a lot like scratching, said Diana Bautista, an assistant professor of cell and developmental biology at the University of California, Berkeley. Her research includes studying various strains of itchy mice that are models for human ailments.
Recent research has shown that substances other than histamine, released from inflammatory cells, are involved in chronic itching, along with three types of nerve cells, Bautista said. Drug companies are trying to find ways to block those substances.

One of the most important advances in the field was reported in the journal Nature in 2007 by a Washington University team led by Zhou-Feng Chen, who is now director of the itch centre. Working with mice, his team was studying receptors, molecules on cells that respond to certain chemical signals to change the cells’ behaviour.

The group was the first to find a receptor in the spinal cord that was specific for itching, called gastrin-releasing peptide receptor. The discovery helped prove that signals for itching and pain travel on different pathways.

Chen said that mice with the receptor blocked did not itch. Nor was the group without a receptor harmed by the lack of it. “If you block function of this receptor alone, you pretty much stop chronic itching,” he said. The receptor is present in humans too, and Chen said it might be possible to develop a drug to block it.

For many patients, new treatments cannot come soon enough. One of them was a boy who had scratched his arms and legs raw. Doctors had referred him and his family to a psychiatrist. Now 18, Joshua Riegel said, “They said I was doing it to manipulate my parents.” Thus began what he calls “that weird part of my life where they thought I was mentally ill”.

He was 12 or 13 when the psychiatrist prescribed antidepressants, which he dutifully took for two or three years. But they brought on terrible side effects: at one point, he was hospitalised with suicidal thoughts.

As a last resort, his parents took him from their home in Hillsville, Virginia, to see Yosipovitch. Tests found a rare form of a genetic disease that was causing a particularly destructive set of symptoms: intense itching and skin so fragile that scratching ripped it to shreds.

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