ADELAIDE: Pain receptors in the African naked mole-rat differ from other animals, giving them a reduced sensitivity to acid, a new study has found.
When people experience tissue inflammation, the extracellular fluid around the cells becomes acidic and this contributes to pain. This is comparable to the stinging experienced if you drip lemon juice on a cut or scratch.
However, mole-rats are unique in that they don’t suffer when there is a build-up of acid in their bodies. Scientists have now discovered the molecular basis for this phenomenon and the findings, published in Science today, may help in the development of treatments for people in chronic pain from injury or infection.
“We now understand how the mole-rat has become insensitive to acid – through a change in one gene,” said co-author Gary Lewin, molecular physiologist at the Max-Delbrück Centere for Molecular Medicine in Berlin-Buch, Germany.
The mole-rat lifestyle
African naked mole-rats live underground in the deserts of East Africa. Groups of up to 300 individuals live together in poorly ventilated tunnels with low oxygen levels. Inside the burrows the carbon dioxide concentration can be as high as 10% whereas normal atmospheric levels of carbon dioxide are around only 0.04%.
High levels of carbon dioxide can cause a build-up of acid in body fluids (tissue acidosis). For all other vertebrates, acid in body tissues causes discomfort and sensitivity; however, previous studies found that mole-rats did not show signs of irritation or distress when exposed to acid. Therefore, insensitivity to acid appears to be an adaptation to the extreme conditions in their habitat.
In neurons, certain sodium channels, labelled Nav1.7, are critical for pain perception. These sodium channels initiate nerve impulses which lead to aching and piercing sensations. In this study, the researchers found that these sodium channels in the naked mole-rat stopped the transmission of nerve impulses to the brain. This is the same way that local anaesthetics create feelings of numbness.
“Amazingly in the naked mole-rat, protons actually block these channels… paradoxically the acid is acting like a local anaesthetic,” said Lewin.
The scientists first tested whether acid excites the neurons in naked mole-rats and surprisingly found that it did. This led them to question whether there was something preventing the animal from producing nerve impulses in the pain receptors. They sequenced the genes for the sodium channels and looked for differences between the mole-rat genes compared to other animals.
Blocked sodium channels stop pain
When the scientists changed three amino acids in the sodium channel Nav1.7 of a human gene, they could make the channel shut down and create the numbing effect observed in the naked mole-rat.
These results show that tiny changes to one gene can produce huge differences in an animal’s behaviour. If mole-rats didn’t have this slight genetic mutation they would be in constant distress in their subterranean habitat, as their tissues are constantly exposed to acidity. “This study shows that evolution can come up with very interesting solutions to problems,” said Lewin.
Nick Spencer, a neuroscientist at Flinders University in Adelaide commented on the findings. “This study reinforces that specific genetic mutations which improve the wellbeing of an organism are preserved – a wonderful example of natural selection at work.”
Spencer was also interested in the implications for medical research. “The knowledge gained from this study reinforces that specific therapies to selectively silence pain arising from a specific organ are one day a realistic possibility,” he said.
This may mean that more effective treatments for tissue damage and injury may be influenced by the unusual physiology of the humble mole-rat.
Original paper in Science
Max-Delbrück Centere for Molecular Medicine
Naked mole-rat – Wikipedia