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Gene crucial for feeling pain found: discovery may lead to better drugs for chronic sufferers.

Mutations in a previously unscrutinized gene can leave people dangerously indifferent to harm, researchers report May 25 in Nature Genetics.

Certain changes to this gene, PRDM12, rob people of the ability to feel pain, leading to unintentional injuries such as scarred tongues or scratched corneas. A deeper understanding of how pain is blocked in these rare cases could ultimately lead to better pain treatments.

"It's promising, but there's a long way to go," says Simon Halegoua, a neuroscientist at Stony Brook University in New York.

Scientists already knew that mutations in another gene, SCN9A, can cause congenital insensitivity to pain (SN: 6/30/12, p. 22). In the new study, Geoff Woods of the University of Cambridge and colleagues identified 11 families that carry mutations in PRDM12. The gene encodes instructions for making a protein that helps pain-sensing nerve cells, called nociceptors, develop. Affected people are missing some nociceptor fibers that carry pain signals to the brain, the researchers found. "You need PRDM12 present to grow your pain neurons," Woods says.

The PRDM12 protein helps orchestrate nociceptor development early in gestation, studies on human cells and frog and mouse embryos suggest. But the protein is also present after birth, hinting that it helps keep fully formed pain-sensing neurons working. The protein seems to be present only in pain cells and their precursors, as opposed to the protein made by SCN9A, which is found in the pancreas and some other locations.

"What's exciting is that this is probably the most pain neuron-specific gene that we know of," Woods says. That specificity raises tantalizing prospects for developing a drug that could tamp down chronic pain without causing problems elsewhere. "The more we can understand about how these nociceptors work," he says, "the more likely we are to have treatments for the vast numbers of people with chronic pain conditions."

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Title Annotation:BODY & BRAIN
Author:Sanders, Laura
Publication:Science News
Date:Jun 27, 2015
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