No-pain gene discovered

Genetic culprit for inability to perceive pain could lead to new treatments for chronic pain

pain path

HOW IT HURTS  Rare mutations in the gene PRDM12 prevent proper development of pain-sensing fibers that carry pain signals from the skin to the brain, rendering people impervious to pain, a new study suggests. 

E. Otwell

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, scratched corneas and missing digits. A deeper understanding of how pain is blocked in these rare cases could ultimately lead to better treatments for people who suffer from pain.

“It’s promising, but there’s a long way to go,” says neuroscientist Simon Halegoua of 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 in England and colleagues identify 11 families who carry mutations in PRDM12. The gene contains 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 study suggests. “You need PRDM12 present to grow your pain neurons,” Woods says.

The PRDM12 protein probably helps orchestrate nociceptor development early in gestation, Woods says. But the protein is also present after birth, hinting that it helps keep fully formed pain-sensing neurons working well. 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 several other locations.

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

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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