They're not much to look at, but mole-rats are pretty amazing animals. Among a range of other biological oddities, these weird little rodents have a remarkable resistance to pain that's not seen in other mammals, and now researchers have a better understanding of why. A new study has uncovered the molecular reasons for the pain insensitivity, which could eventually lead to new pain relief techniques for human use.
Mole-rats boast quite a list of superpowers. Aside from being impervious to pain, they almost never get cancer, they can mimic plants to survive without oxygen for long periods, and even seem to violate fundamental biological laws of aging. Since these are all traits that humans could benefit from, the quirky creatures have been extensively studied for years.
For the latest study, a team of researchers from the University of Illinois at Chicago, the Max Delbrück Center for Molecular Medicine and the University of Pretoria investigated the mole-rat's pain resistance in more detail.
They began by testing the pain responses of eight mole-rat species, and how their reactions compared to mice. To do so, they exposed the paws of animals to three compounds that would induce mild pain-like sensations: capsaicin (the stuff that makes chili peppers hot), AITC (the hot compound in wasabi), and an acidic solution about the strength of lemon juice. Pain responses were measured through behaviors like how long the animals spent licking their paws afterwards.
The team found that three mole-rat species seemed to be immune to the acidic solution, while two others had no response to capsaicin. The naked mole-rat was the only species immune to both of these. But perhaps the strangest finding was that one species, the highveld mole-rat, turned out to be immune to AITC.
"This is an awesome finding because the highveld mole-rat is the only mammal known to be immune to 'wasabi pain'," says Thomas Park, co-author of the study. "It turns out that highveld mole-rats share their tunnels, their natural environment in Africa, with a stinging ant species, the natal droptail ant. The ant's sting normally activates the same pain receptors that respond to wasabi. Over time, the highveld mole-rats evolved to become unaffected by the sting."
To find out how the rodents resist this kind of pain, the researchers analyzed samples of their spinal cord and nerve tissue. The most interesting finding was that the nerves of highveld mole-rats had far more "leak channels" called NALCN on their surface, which would serve to disrupt the pain signals.
"Nature and evolution solved a pain problem for the highveld mole-rat," says Park. "The leak channels make the nerves unable to convey messages about wasabi pain to the brain. Instead of delivering the signal from the receptor to the brain, the leak channels divert the signal."
To test out the connection, the team used a drug to block the activity of NALCN. Sure enough, the mole-rats suddenly became sensitive to the wasabi compound – at least for a short time. Armed with that knowledge, the research could lead to new pain relief treatments for human patients.
"When we find out how to add leak channels to our own pain cells, we'll have a new way of fighting pain, without the side effect of addiction from external pain killers," says Park.
The research was published in the journal Science.
Sources: Max Delbrück Center, University of Illinois at Chicago