Wednesday, October 12, 2016

How naked mole rats conquered pain—and what it could mean for us | Science | AAAS

Although it has a face—and body—that only a mother could love, the naked mole rat has a lot to offer biomedical science. It lives 10 times longer than a mouse, almost never gets cancer, and doesn't feel pain from injury and inflammation. Now, researchers say they've figured out how the rodents keep this pain away.

"It's an amazing result," says Harold Zakon, an evolutionary neurobiologist at the University of Texas, Austin, who was not involved with the work. "This study points us to important areas … that might be targeted to reduce this type of pain."

Naked mole rats are just plain weird. They live almost totally underground in coloniesstructured like honey bee hives, with hundreds of workers servicing a single queen and her few consorts. To survive, they dig kilometers of tunnels in search of large underground tubers for food. It's such a tough life that—to conserve energy—this member of the rodent family gave up regulating its temperature, and they are able to thrive in a low-oxygen, high–carbon dioxide environment that would suffocate or be very painful to humans. "They might as well be from another planet," says Thomas Park, a neuroscientist at the University of Illinois, Chicago.

Gary Lewin, a neuroscientist at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association in Berlin, began working with naked mole rats because a friend in Chicago was finding that the rodent's pain fibers were not the same as other mammals'. In 2008, the studies led to the finding that naked mole rats didn't feel pain when they came into contact with acid and didn't get more sensitive to heat or touch when injured, like we and other mammals do. Lewin was hooked and has been raising the rodents in his lab ever since. They are a little more challenging than rats or mice, he notes, because with just one female per colony producing young, he never really has quite enough individuals for his studies.

So instead of studying the whole animals, he began isolating single nerve cells from the mole rats and investigating them in lab dishes to track the molecular basis of the rodent's pain insensitivity. The pain pathway is kicked off when a substance called nerve growth factor is released by injured or inflamed cells. This factor binds to a protein on the pain-cell surface, a so-called receptor named TrkA, which relays the "pain" message throughout the cell. In us and other mammals, that message increases the activity of a molecular pore, called the TRPV1 ion channel, causing the cell to become more sensitive to touch or heat. "So the cell says 'It hurts more,'" Lewin explains.

But that doesn't happen in naked mole rats. Lewin evaluated the workings of the animal's pain pathway components by mixing them with those of standard rats and putting the combinations in immature frog eggs. For example, the naked mole rat TRPV1 channel sensitized the egg to acid and heat when the rat TrkA was put into the egg cell with it. Thus, Lewin and his colleagues narrowed down the breakdown in this pathway to the TrkA receptor itself. The naked mole rat version of TrkA failed to activate the ion channel as efficiently as the rat version of TrkA, Lewin and his colleagues reveal today in Cell Reports.

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