The naked mole rat can't feel pain from acid burns. Now we know why.S

The naked mole rat is quickly becoming one of my favorite mammals ever. The glabrous little buggers live decades longer than most other rodents, never develop cancer, and have mastered the enviable skill of being able to run backwards as quickly as they do forwards.

They are also, as it turns out, completely impervious to the excruciating pain of an acid burn — and now researchers think they know why.

It all boils down to the balance of protein structures called ion channels. When you come into contact with acid, pain-sensing neurons called nociceptors become excited. When they do, they relay a message to your brain, telling it ow, that acid really hurts.

You'll find ion channels in every cell of your body, helping manage any number of molecular processes; but in sensory neurons (like nociceptors), they help regulate whether or not the neuron gets excited enough to actually begin transmitting a signal brainward. Acid-mediated nocicepter activity is largely controlled by two main acid-sensing ion channels. So when neuroscientist Ewan St. John Smith and his colleagues decided to look for an explanation for the mole rat's acid insensitivity, they naturally hypothesized that one or both of these channels would simply be missing in the mole rats.

The naked mole rat can't feel pain from acid burns. Now we know why.S

They were wrong.

Because it turns out that mole rats — despite being the only known vertebrates that are insensitive to the painful stimulus of acid — have the same two fully-functional, acid-sensing channels regulating their pain receptors as the rest of us, and even produce the channels in similar quantities. And this is where things get interesting.

Smith and his colleagues decided to look at a different class of channel, called voltage-gated sodium channels, or Navs for short. Just like the two acid-sensing channels, Navs play an important role in regulating whether or not a neuron fires.

Incredibly, when the researchers exposed the nocicepters from naked mole rats and mice to acid, they found that the signal passing through the Nav channels in naked mole rats was inhibited by 63 percent — significantly more than the 43% inhibition observed in mice. Inhibition of the Nav channel, in turn, prevents the nociceptor from firing; if the nociceptor doesn't fire, no pain is felt.

In the interest of finding out why the naked mole rat's Nav channels inhibit nocicepter firing so effectively, they decided to look more closely at one of its Navs in particular: Nav1.7.

Among voltage-gated sodium channels, Nav1.7 is thought to play an especially important role in determining whether or not a pain-sensing neuron shoots off a signal to your brain. For one thing, it's found almost exclusively in nociceptors. (Remember, nociceptor = pain-sensing neuron.) Furthermore — and this doesn't happen often — humans lacking the Nav1.7 channel have been known to feel no pain whatsoever. In contrast, disorders like erythromelalgia — a chronic skin disease characterized by periodic episodes of severe burning sensations — are often associated with activating Nav1.7 mutations.

The naked mole rat can't feel pain from acid burns. Now we know why.S

Searching the naked mole rat genome revealed two mutations in the gene that codes for its Nav1.7 channel, and these mutations render the channel especially sensitive to proton block; and blocking the channel, you'll recall, prevents the excitation of the nociceptor.

Here's why that's important: be you mouse, human, or naked mole rat, exposure to acid is going to cause your acid-sensing channels to holler at your nociceptors, telling them to fire; and be you mouse, human, or naked mole rat, exposure to acid is going to cause your voltage-gated sodium channels to holler at your nociceptors, as well — only they'll be instructing them not to fire. The crucial difference, however, between the naked mole rat and the rest of us, is that its voltage-gated sodium channels shout louder than ours, and ultimately win out over its namby-pamby (relatively speaking) acid-sensing channels.

Pretty impressive for a hairless, backpedaling "sabre tooth sausage," wouldn't you say?

The researchers' findings are published in the latest issue of Science
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