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No beauty, no pain: How naked mole rats handle the heat

The mole rat could eat as many hot peppers as it wanted. Here's how. (Thomas Park/University of Illinois at Chicago)

Naked mole rats are, frankly, outrageously weird. The hairless rodents are basically coldblooded, a freakish quirk for a mammal. They live for decades, while mice — nearly identical from a genetic standpoint — live for just a few years. They experience a shockingly low rate of cancer. And perhaps most intriguingly, they're impervious to certain kinds of pain.

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Researchers have noted that Heterocephalus glaber (also known as the “sand puppy,” which seems generous) doesn't experience “thermal hyperalgesia.” That's a phenomenon most animals, including humans, are familiar with: When you get a bit of sunburn, you know that a warm shower will hurt like the dickens. It's the increased sensitivity of pain receptors in damaged tissues, telling your body to be gentle with a wounded area. In some humans, this sensitivity can go haywire and cause chronic pain. In others, a hyposensitivity can leave one dangerously insensitive to pain, making it difficult to judge when tissue is being injured.

Naked mole rats don't really experience this sensation, probably because they live in huge colonies that pack into close, hot quarters where such sensitivity would make life miserable. In a study published Tuesday in Cell Reports, scientists tried to figure out the mechanism behind their (metaphorically) thick skin.

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“I call them extremophile mammals. That’s the way I treat them, just like extremophile bacteria,” said lead study author Gary R. Lewin, a professor at the Max-Delbruck Center for Molecular Medicine in Berlin. He's fascinated by their ability to live in hot, cramped quarters with little food. He thinks that their insensitivity to pain — and most of their other strange quirks, including the inability to regulate body temperature — simply serve to make their bodies more efficient.

Because most animals experience thermal hyperalgesia, Lewin and his colleagues had a good understanding of how the pain pathway works: When the tissue around sensory neurons is inflamed and exposed to heat, the body releases a substance called nerve growth factor (NGF). When NGF binds to a pain receptor called TrkA, it triggers the opening of a pore in the neuron's membrane, signaling the brain to feel pain even though temperatures aren't necessarily high enough to cause harm. It's the same pathway that causes hot peppers to burn your mouth.

The question was where in this chain of events naked mole rats jumped ship.

By isolating neurons from mole rats and closely-related rodents, Lewin and his team found that the buck stops at the TrkA receptor: It took 10 times as much NGF to make a naked mole rat TrkA receptor behave the same way as one from a mouse, or even from another species of mole rat.

“Only maybe one to three amino acids were really unique to the naked mole rat,” Lewin said. “Fiddling with just a couple of those amino acids was enough to make this receptor hyposensitive.”

Naked mole rats might not be pretty, but they managed to evolve an efficient system for sensing pain without giving it up entirely, which is a condition that usually proves disastrous for animals.

Lewin thinks that's a great takeaway for researchers working on tweaking TrkA receptors in humans to fight chronic pain.

"This study is not going to tell them how to do that,” he said, "but I think it’s cool that 30 million years ago, the naked mole rat figured it all out. Evolution has already done it.”

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