Naked mole-rat pain resistance puzzle solved

They might not be the prettiest, but naked mole-rats have an extraordinary tolerance to pain, and a new study might have worked out why.

Published: October 11, 2016 at 1:00 pm

Naked mole-rats are fascinating, if a little unsightly, creatures. Long living and cancer resistant, with incredibly low rates of metabolism pushing the boundaries of what it means to be a warm-blooded mammal.

In 2003, the accidental discovery of their extraordinary tolerance to pain added to the mysteries surrounding them, but a new study hopes that by understanding how they acquired this resistance, we may be able to better understand our own pain mechanisms.

Stopping the pain train

Anyone who’s eaten a spicy meal knows the sensation their mouth feeling a lot hotter after the first mouthful, however your food hasn’t suddenly warmed up. This sensation is known as thermal hyperalgesia and this is one of the struggles of modern life that the naked mole-rat manages to avoid.

This response is caused when heat or inflammation causes molecules to bind around a sensory neuron receptor called TrkA, starting a signalling cascade, telling the brain to feel a burning sensation, even at normal temperatures.

In the study, published in Cell Reports, it was discovered that a small change in this TrkA receptor is what differentiates naked mole-rats from other animals.

When compared to similar molecules in mice cells, the study revealed a 3-amino acid change in the naked mole-rat TrkA molecule that significantly reduces it’s sensitivity, requiring roughly ten times the amount of stimulation.

"Even though the naked mole rat's version of the TrkA receptor is almost identical to that of a mouse or a rat, it has a very significant effect on the animal's ability to feel pain," says Gary R. Lewin, professor at the Max-Delbruck Center for Molecular Medicine in Berlin, Germany, and lead author of the study.

It may even be that evolution has selected the path of TrkA to be less functional, but not to the extent of putting the animal in danger.

To this same end by adulthood a naked mole rat will lose around two-thirds of their pain receptors when compared to other mammals.

Stay cool, mole rat

Although naked mole-rats are unlikely to encounter the spicy molecule capsaicin found in a chilli pepper, they do work surprisingly hard in the harsh desert climate and their underground burrows are tight quarters, where close contact could make the thermal hyperalgesia reaction uncomfortably hot. Limiting this reaction allows the naked mole rats to waste less energy, making them feel more comfortable in these hot environments.

"They live in desert regions underground, and they have to do a lot of work to get their food," says Lewin. "They have the lowest metabolic rate of any mammal. Evolution has shut down everything that is not absolutely necessary - including extra nerve receptors."

Next Professor Lewin and his team plan to continue their research by breeding the naked mole-rat TrkA molecule into a strain of mice.