THE AFRICAN NAKED mole rat may be one of nature’s oddest-looking creatures, but it’s also the toughest.

These small rodents can live for 32 years, they are cancer-resistant, and they are impervious to some types of pain.

Now, new research has pinpointed the evolutionary change that made the naked mole rat so uniquely pain-free, according to a study published on Tuesday in Cell Reports.

“We think evolution has selected for this tweak just subtly enough so that the pain signaling becomes non-functional, but not strong enough that it becomes a danger for the animal,” says lead author Gary R Lewin, a professor at the Max-Delbruck Center for Molecular Medicine in Berlin, Germany.

Imagine the sting of entering a hot tub with a bad sunburn. The naked mole rat wouldn’t be bothered, but most animals would sense this as thermal hyperalgesia, and the scientists who conducted the study have a good idea of what goes on at a cellular level when this happens.

In response to high temperatures and inflammation around sensory neurons, nerve growth factor (NGF) molecules bind to a receptor called TrkA.

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This kicks off a cascade of chemical signals that “sensitise” an ion channel — called TRPV1 — on the surface of the sensory neuron so that it opens. Once TRPV1 opens, it results in sensory nerve firing that tells the brain to register pain at temperatures that are not normally painful.

Through more than a dozen carefully designed experiments, Lewin and colleagues found what differentiates the naked mole rat from other animals in this process — a small change in their TrkA receptor.

For example, if the scientists swapped out the TRPV1 channels in a mouse cell for naked mole rat versions of TRPV1, then thermal hyperalgesia occurred normally. But if a cell had a common rat TRPV1 and a naked mole rat TrkA, then the cell couldn’t sense thermal hyperalgesia.

Losing thermal hyperalgesia might help the naked mole rats survive in their crowded underground colonies, where the close contact can be uncomfortably hot but thermal hyperalgesia may not be helpful in this warm environment. And it’s possible that losing sensory neurons as adults may help the animals conserve energy.

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