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Mouse Impervious to Scorpion's Sting

Who would win in a fight: a bark scorpion or a grasshopper mouse? It seems like an easy call. The bark scorpion (Centruroides sculpturatus) delivers one of the most painful stings in the animal kingdom—human victims have compared the experience to being branded. The 25-gram grasshopper mouse (Onychomys torridus) is, well, a mouse. But as you can see in the video above, grasshopper mice routinely kill and eat bark scorpions, blissfully munching away even as their prey sting them repeatedly (and sometimes right in the face). Now, scientists have discovered why the grasshopper mice don’t react to bark scorpion stings: They simply don’t feel them.

Evolutionary neurobiologist Ashlee Rowe of Michigan State University in East Lansing has been studying the grasshopper mice’s apparent superpower since she was in graduate school. For the new study, she milked venom from nearly 500 bark scorpions and started experimenting. When she injected the venom into the hind paws of regular laboratory mice, the mice furiously licked the site for several minutes. But when she injected the same venom into grasshopper mice, they licked their paws for just a few seconds and then went about their business, apparently unfazed. In fact, the grasshopper mice appeared to be more irritated by injections of the saline solution Rowe used as a control.

Rowe knew that grasshopper mice weren’t entirely impervious to pain—they reacted to injections of other painful chemicals such as formalin, just not the bark scorpion venom. To find out what was going on, she and her team decided to determine how the venom affects the grasshopper mouse’s nervous system, in particular the parts responsible for sensing pain.

Luckily for Rowe’s team, feeling pain involves just a few of the body’s many possible chemical channels, so they were able to quickly zero in on two of them: Nav1.7 and Nav1.8, which work by moving sodium ions in and out of cells. In mammals, Nav1.7 initiates a pain signal, while Nav1.8 transmits that signal to the brain. Both channels need to be activated for something to hurt.

In a petri dish, Rowe and colleagues could tell that the bark scorpion venom works by targeting Nav1.7 in cells from lab mice and grasshopper mice. But in grasshopper mice, Nav1.8 comes to the rescue with a neat trick: It shuts down in the presence of bark scorpion venom. “The [pain] signal might get generated by sodium channel 1.7, but it does not get sent to the brain by 1.8,” Rowe says. Her team reports its results online today in Science.

“They’ve actually shown the molecular basis by which an animal has evolved [pain] resistance, and that’s very cool,” says Glenn King, a structural biologist at the University of Queensland in Australia who was not involved in the research. Pain resistance, even to specific stimuli like scorpion venom, is an unusual adaptation, Rowe says. Typically, pain “prompts us to take care of ourselves,” she says, alerting us to dangerous situations, like a nearby flame or a cut that could become infected, and teaching us to avoid them in the future. She speculates that grasshopper mice evolved their resistance to bark scorpion venom so that they could eat the arthropods, which are abundant in the Arizona desert where the mice live. Bark scorpions “represent a really valuable food resource” in an ecosystem where other prey is scarce, she says.

Although grasshopper mice can usually feel other kinds of pain, Rowe observed that they seem to be temporarily insensitive to other painful stimuli after a dose of bark scorpion venom shuts down their Nav1.8 channels. She hopes this trick might be useful for engineering a new class of painkillers for humans. “The ideal painkiller is one that you take and your pain goes away but nothing else is affected,” says Ewan Smith, a neuroscientist at the University of Cambridge in the United Kingdom who was not involved in the current research. Because Nav1.7 and Nav1.8’s only jobs are to trigger pain, he says, a drug that targeted one or both of them as well as bark scorpion venom does would inhibit pain but let you keep other types of sensations (no more numb faces after a visit to the dentist). What’s more, it would have no side effects or risk of addiction because it would affect the pain pathways and nothing else, Smith says. Now that’s a superpower worth writing home about.

*Correction, 28 October, 3:50 p.m.: Ashlee Rowe is now at Michigan State University, not the University of Texas, Austin, as was originally reported.