The naked mole rat, native to East Africa, has no shortage of quirky biological features: it resides underground in near darkness, lacks hair, lives for more than 2 decades, and doesn't develop cancer. Now, another one of its unusual traits has been explained—its inability to feel pain from acid. The adaptation allows the mole rats to thrive in their communal tunnels, where acid levels rise because excess carbon dioxide builds up as the animals exhale.
"Understanding more about how pain pathways work is critical to developing new ways to treat pain," says the lead author of the new study, neuroscientist Ewan St. John Smith of the Max Delbrück Center for Molecular Medicine in Germany.
Smith and his colleagues previously discovered that when they injected small amounts of acid into the paw of a naked mole rat, the animals showed no response. Mice, on the other hand, immediately pull back their paw and lick it. The pain is equivalent to what a person might feel when a cut is exposed to lemon juice. The acid is known to be sensed through nociceptors, receptors on pain-sensing neurons.
Smith expected that when he examined the neurons of the naked mole rats, they'd be missing the acid receptors, or have nonfunctional ones. But the naked mole rat nociceptors were present and functioned the same as those of mice. So Smith's team turned its attention toward channels that direct the flow of sodium across the cell membrane; such channels are responsible for generating a neuron's action potential—the electrical signaling wave that moves across a neuron when it's excited, to transmit a signal to the brain. The researchers discovered two mutations in a sodium channel that's found almost exclusively in pain-sensing neurons. The mutations make the channel, called NaV1.7, more easily blocked than it usually is. In naked mole rats, when acid molecules bind nociceptors to excite a neuron, they simultaneously block the NaV1.7 channel, the researchers discovered. This stops the excitation from being propagated through the neuron and from sending a pain signal to the animals' brains.
When human or mouse neurons detect acid, the acid molecules similarly both activate the neuron and partially block the sodium channel. But the activation wins out. In naked mole rats, the difference is that NaV1.7 is entirely blocked, Smith's team reports online today in Science.
Mutations in NaV1.7 have previously been linked to the pain disorder erythromelalgia, a chronic disease characterized by periodic episodes of burning pain on the skin. And loss of the channel is known to lead to rare cases of people who are unable to feel pain. The finding in naked mole rats sheds new light on how to block the channel, says Smith, a possible avenue for future pain-killers.
"This is an extremely thorough study and the results are very exciting," says neuroscientist Harold Zakon of the University of Texas, Austin, who was not involved in the research. "Naked mole rats are becoming a more widely studied species because of their interesting adaptations to the subterranean environment. This explains one of those adaptations."
The finding that acid sensing in particular relies on both the nociceptor and the sodium channel is one that needs to be further investigated, Zakon says. "This is a balance between transmitting pain and inhibiting pain," he says. "We need to understand that better."