Yan-Gang Sun and Zhou-Feng Chen, Nature (7 July 2007)

Relief?
The itch protein GRPR (red) in a section of spinal column.

Scratch That Gene

Scratchers of the world take heart. Researchers have identified the first gene in the central nervous system that is responsible for itching. Although other itch genes are known, this is the first one directly linked to the brain and could pave the way for novel drugs to sooth serious itching.

The irritating culprit made by the gene is gastrin-releasing peptide receptor (GRPR). Researchers have been studying the gene for its role in pain, but no one ever tied it to itching. A team led by geneticist Zhou-Feng Chen of Washington University School of Medicine in St. Louis, Missouri, started looking at GRPR because it was interested in pain genes. GRPR is found only in a few spinal nerve cells that send pain and itch signals to the brain. The team soon discovered that the receptor wasn't essential to perceiving pain; mice whose GRPR genes had been knocked out responded normally to various types of pain from heat, inflammation, and mechanical pressure.

The researchers then tested whether GRPR is required for feeling itchy by injecting several itch-inducing compounds into the knockout mice, including histamines--the substances responsible for the itchiness of allergies. The mutant mice didn't scratch anywhere near as much as the normal mice did in response to the injections. Conversely, when the scientists injected normal mice with a substance mimicking the gastrin-releasing peptide, they scratched even more, the team reports online today in Nature.

The authors believe this signaling pathway offers a promising new target for chronic itching. This problem, often intractable, stems from a host of maladies, from skin disorders to tumors.

"It's an excellent study and provides a new molecular target ... that may be exploited to relieve itch," says Earl Carstens, a neuroscientist at the University of California, Davis.

Jeffrey Mogil, who heads the pain genetics lab at McGill University in Montreal, Canada, seconds that conclusion, calling GRPR "an eminently druggable target."

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