Why naked mole rats feel no pain

A naked mole rat can be drenched in acid and not feel a thing – and boils down to a subtle change in their pain receptors, a new study reveals.

The bizarre naked mole rat lives underground in east African desert and is unique for a number of reasons: it can live up to 30 years, it’s cancer-resistant and it displays some of the most efficient oxygen use in the animal world.

But its most fascinating trait is its imperviousness to pain. Now, researchers in Berlin are studying the rodent’s molecules in great detail to figure out the genetic selection that has led to this superpower.

The research team, comprising members in Germany, South Africa and the UK, focused the study on the rodent’s ability to withstand extreme temperatures without feeling pain.

The naked mole rat is the only mammal that can shift its body temperature to match the environment – a trait thought to be linked to the species’ unforgiving habitat.

“They live in desert regions underground, and they have to do a lot of work to get their food,” explains co-author and Max Delbrück Centre for Molecular Medicine biologist Gary Lewin.

“They have the lowest metabolic rate of any mammal. Evolution has shut down everything that is not absolutely necessary – including extra nerve receptors.”

In their study, published in Cell Reports, the researchers wanted to take a look the differences at a cellular level between mole rats and other animals that feel pain.

In particular, they used cellular processes surrounding hyperalgesia – the heightened sensitivity that occurs when an animal’s tissue is inflamed, as you might feel a slap on sunburn more painful than one on unburnt skin.

When humans experience hyperalgesia, our nerve growth factor molecules bind to a receptor called TrkA.

This kickstarts a chemical process that eventually sends a signal to the brain to register pain at temperatures we would usually find unacceptable.

Mole rats don’t experience hyperalgesia, so the research team recreated the chemical process in mice, which have similar pain sensitivity rates to us humans, replacing various molecules and cells with those of mole rats.

According to their findings, the difference between the two species comes down to a couple of swapped amino acids on one section of the mole rat’s TrkA receptor.

These changes don’t mean that mole rats are not completely insensitive to pain, but are hyposensitive.

This is a crucial difference, because the lack of awareness of pain would bring a host of problems.

“We think evolution has selected for this tweak just subtly enough so that the pain signalling becomes non-functional, but not strong enough that it becomes a danger for the animal,” Lewin explains.

When it comes to us humans, mutations in the genes that encode nerve growth factor molecules can lead to pain insensitivity conditions. These are extremely dangerous and often lead to infection and disease.

“Mutations in the TrkA gene are highly detrimental in humans, but here we show that evolution has selected for sequence change(s) in the naked mole rat gene that are not only functionally powerful, but also compatible with species survival and continued fitness.”