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Scorpion venom kills pain in mice

Toxin works with nerve proteins to block distress signals’ journey to brain

NO PAIN  An Arizona bark scorpion makes a tasty lunch for the carnivorous southern grasshopper mouse. Proteins in the mouse’s nerves prevent pain signals triggered by the scorpion’s sting from reaching the brain.

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Tiny desert-dwelling rodents have found a way to take the sting out of scorpion venom.

A protein in the nerves of southern grasshopper mice hijacks the venom’s toxins, silencing pain signals that usually race to the brain when scorpions strike. The protein and venom together can even numb the animals to other types of agony, researchers report in the Oct. 25 Science.

“In these mice, the venom actually works like a painkiller,” says neuroscientist Frank Bosmans of Johns Hopkins University who was not involved with the work.

The Arizona bark scorpion, Centruroides sculpturatus, wields particularly nasty venom. “It’s pretty painful,” says study coauthor Ashlee Rowe, an evolutionary neurobiologist at Michigan State University in East Lansing. “People say it feels like being branded, or burned with a cigarette, and then driving a nail in.” A hefty dose of bark scorpion venom can kill infants and small children.

Because the venom is so toxic to mammals, Rowe thought that bark scorpions must use it to defend themselves from mammalian predators. She decided to take a look at southern grasshopper mice, Onychomys torridus, carnivorous rodents that chow down on scorpion species less toxic than bark scorpions. Other researchers had guessed that grasshopper mice might shun bark scorpions, or somehow dodge their stings.

About a decade ago, Rowe collected wild scorpions and mice in Arizona and placed the captured animals in a terrarium. The mice devoured the poisonous pests and didn’t seem to mind getting stung.

To investigate the animals’ high pain tolerance, Rowe and her team injected a drop of venom into the hind paws of house mice and grasshopper mice, and then timed how long the animals tended their wounds. House mice licked their injured paws for about four minutes, while grasshopper mice licked for just a few seconds. In the grasshopper mice, the venom injection even blocked pain from a follow-up injection of formalin, a chemical that provokes a burning sensation.

The researchers suspected that bark scorpion venom might somehow halt pain messages’ journey to the brain. In humans and house mice, venom toxins switch on a pain signal using proteins embedded in nerve cells in the skin. These proteins, called sodium channels, operate tiny gates to control the flow of sodium into the cell.

Venom cues the gates to open, letting sodium flood in and triggering neighboring gates to open. The domino effect lets a pain signal race to the brain.

But when the researchers dissected pain-sensing nerves from grasshopper mice and added venom, one type of channel stopped the usual flow of sodium.  

If sodium can’t flow in, the pain signal peters out, says neuroscientist Thomas Park of the University of Illinois at Chicago. When scorpions sting the mice, he says, “The nerves say, ‘No, I’m not going to send that signal up.’” And when venom is around, the nerves can block pain signals from other sources too.

The mice’s pain-avoiding strategy is similar to that used by naked mole rats in Africa, Park says. Those animals resist pain from acidic environments by shutting down a different type of sodium channel. Park thinks other animals may also deal with pain in similar ways.

The findings will probably interest people designing pain-relieving drugs, says molecular neurobiologist Gary Lewin of the Max Delbrück Center for Molecular Medicine in Berlin. “Drug companies have been trying for at least the last 15 years to make specific molecules that block these channels,” he says.  

“What’s nice about this story is that here comes evolution and actually shows how it can be done.”

SHAKE IT OFF A southern grasshopper mouse tussles with and then devours an Arizona bark scorpion. The scorpions’ venom delivers agony to many mammals, but proteins in the grasshopper mouse’s nerves block pain signals from traveling to the brain. Courtesy of Science/AAAS

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