Acid, wasabi, chillies: mole-rats couldn’t give a toss
Several species of African rodent display remarkable insensitivity to pain, hinting at new ways to manage it in humans. Paul Biegler reports.
Scientists have discovered that a half-blind African mole-rat can take about as much wasabi as you can throw at it, for reasons that could lead to new painkillers in humans.
The team, led by Gary Lewin at the Max Delbrück Centre for Molecular Medicine in Berlin, Germany, and including colleagues in South Africa and Tanzania, co-opted nine species of mole-rat, from three families in a test of culinary-oriented pain sensitivity.
The burrowing, buck-toothed natives of East Africa were given paw injections of capsaicin, the compound responsible for the burning sensation of chillies, and allyl isothiocyanate (AITC), which delivers the eye-watering hit of wasabi, the Japanese condiment often eaten with sushi.
For good measure the animals also got a dose of hydrochloric acid.
To see if the critters felt any pain, the team measured how long they spent lifting and licking the affected limb.
Two species were insensitive to the acid, one to capsaicin, and a fourth, the unfortunate-looking naked mole rat (Heterocephalus glaber), displayed a distinct lack of pain to both. Only one rat, however, could hack AITC which, it is worth noting, also gives mustard and horseradish their distinctive punch.
The animal in question was the highveld mole-rat (Cryptomys hottentotus pretoriae) which, the researchers report, was “completely insensitive to AITC”.
A big question is why.
As it happens, AITC is found in plant roots that form a major part of the highveld mole-rat’s diet, so the ability to eat them without a fuss may have emerged as an evolutionary advantage. But an even bigger question, and one that should have pain researchers pricking up their ears, is how the species pulls off its wasabi-beating trick.
To find out, the team looked at genes expressed in part of the rat’s pain-sensing system, the dorsal root ganglia, where sensory nerves connect with the spinal cord to take pain messages to the brain.
They found that one gene, called Nalcn, was present at levels six times higher in the highveld mole-rat than in other species sensitive to AITC. Nalcn, as it happens, controls the entry of sodium into nerve cells; when there is a lot of it, the nerve cells become leaky to sodium, fire less and get worse at taking pain messages to the brain.
The pain-busting properties of overactive Nalcn looked to confer wasabi resistance. But the researchers also wondered if they might explain another curious behaviour of the animal. It shares its burrow with a species that all other mole-rats avoid like the plague; the Natal droptail ant (Myrmicaria natalensis).
“These insects are known for their aggressive nature and highly pungent venom,” says Lewin.
If the highveld mole-rat were impervious to the ant’s bite, it might get a survival edge by being able to cohabit with them.
But how to test the theory?
Continuing the gastronomic vein, the researchers came up with a nasty concoction made from the crushed abdomens of the ants. Applied to the paws of two mole-rat species, that sting syrup led to some serious lifting and licking.
But the same syrup on the paw of the highveld mole-rat was met with indifference.
Up-regulated Nalcn in the species also seemed to confer insensitivity to the ant bite. The researchers, however, needed one final check to be sure.
Verapamil is a drug used for heart conditions and it also blocks the Nalcn-controlled sodium channels in rats. Dosed with it, the highveld mole-rats were now dancing in pain from the ant syrup, something of a slam dunk for the theory that Nalcn, and sodium channels in nerves, are really important in transmission of pain signals.
"From the thousands of genes we were looking at, we had obviously found the very gene responsible for the highveld mole-rat's remarkable pain resistance," says Lewin.
Which could be very good news for a certain larger species.
“This discovery could well lead to the development of highly effective analgesics,” says Lewin.
The research is published in the journal Science.