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To Itch or Not to Itch? It's in the Genes

THURSDAY, July 26 -- Researchers at the Washington University School of Medicine in St Louis were scratching their heads over the genetic roots of pain when they stumbled on GRPR, the gene for itchiness.

The discovery could lead to more targeted remedies for chronic itching caused by everything from eczema to liver and kidney diseases.

GRPR codes for a receptor found in a small group of spinal cord nerve cells where pain and itch signals are transmitted from the skin to the brain. Mice who do not have this gene scratch less in the presence of known itch-inducers, the researchers found.

Traditionally, researchers have had a greater interest in the genetic underpinnings of pain than of itching.

"Many genes have been identified in the pain pathway," lead researcher Zhou-Feng Chen, said in a prepared statement. "But itch research has lived in the shadow of pain research, and no one knew which gene was responsible for itching in the brain or in the spinal cord, until now."

Chronic itching is a widespread problem. Skin disorders such as eczema, illnesses such as kidney failure or liver disease, and cancer therapies and powerful painkillers such as morphine can all lead to itchiness. For some people, itching is bad enough to interfere with sleep or result in scarring from scratching. Effective treatment options for itchy patients are limited.

Writing in the July 25 online issue of Nature, Chen and his team describe research that came about as a result of an effort to find genes in the pain pathway. They identified GRPR as a potential candidate and performed studies on mice missing GRPR in comparison to normal mice.

Although they saw no difference between the mice in terms of pain response, they found a striking change when the mice were presented with itchy substances. While normal mice scratched vigorously, those lacking GRPR scratched little if at all.

The researchers also injected a substance that stimulates the GRPR gene and witnessed an increase in scratching behavior

In the long term, the research results suggest a way to develop anti-itch medication that does not dull pain response. In fact, the researchers noted that there are already pharmaceuticals in the pipeline that could help ease itching.

"Scientists have been studying [the GRPR] receptor for more than a decade," Chen said. "One interesting thing they've found is that GRPR is implicated in tumor growth. As a result of research like this, a lot of substances have been made that block the activity of GRPR. So now, researchers can study the effect of these agents on the itch sensation and possibly move that research to clinical applications fairly soon."

More information

To learn more about itching and the conditions that cause it, visit the U.S. National Institutes of Health.

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Posted: July 2007