News in Science

Scorpion-eating mouse feels no pain

Resisting pain The discovery that a type of mouse feels no pain from scorpion venom has revealed a new strategy for developing pain-killing drugs.

The grasshopper mouse can feast on bark scorpions with impunity, even though the sting from this scorpion can cause "prolonged throbbing pain" in humans, the authors explain in Science.

Not only does the venom appear harmless in the mice, it actually seems to have an analgesic effect, protecting them from other painful stimuli, according to lead author, Dr Ashlee Rowe of Michigan State University in the US.

In a series of experiments, Rowe and colleagues show that the grasshopper mice (natives of the US and Mexico) don't respond to the venom with pain, whereas a normal house mouse does.

But more than that, when the grasshopper mice are exposed first to the venom and then to formalin, which causes discomfort, the formalin has much less effect.

A tale of two channels

To find how the grasshopper mice can be stung without pain the researchers studied the sodium channels found in the nerves that transmit pain signals to the brain.

They looked at two well-known sodium channels known as Nav1.7 and Nav1.8.

These protein channels pass through the membrane of the nerve cell and can let a current of sodium ions flow into the cell, leading it to fire off a message to the brain.

While the scorpion venom binds to Nav1.7 in most animals, Rowe was surprised to find it was binding to Nav1.8 in her grasshopper mice and disabling the channel.

"We found the venom actually blocked the current in 1.8," she says. "1.8 is responsible for transmitting the signal to the central nervous system. Essentially, if you block the current in sodium channel 1.8 you are blocking the signal from getting to the brain. That's why the mice don't feel pain," explains Rowe.

She thinks the discovery of a toxin that blocks Nav1.8 is a first. "I don't think there are any [other] animal toxins out there that block 1.8," she says.

Crucial mutation

Rowe wants to work out exactly which component of the venom is disabling the channel.

"We don't know yet the peptide that's in the toxin - we're still trying to isolate it. I know which fraction of the venom is doing the block but there are about five different peptides in that fraction."

Rowe was able to look at the detailed amino acid sequence of the Nav1.8 channel in the grasshopper mice and compare it with the sequence for house mouse and human Nav1.8 channels.

The grasshopper mice had a glutamic acid residue at a key position in the protein chain, whereas house mice and humans didn't.

This mutation at a crucial spot plays a major role in enabling the scorpion venom to bind to and block the channel's function, she showed.

"Clearly this didn't necessarily evolve in the grasshopper mouse. It probably evolved in a mammalian ancestor and maybe it served some other purpose, but now it enables [grasshopper mice] to kill and consume scorpions," says Rowe.

Interestingly some other animals, including the naked mole rat, also have glutamic acid at this spot.

"As far as I know, none of these other animals are eating scorpions," she says, "but they may be partially insensitive to the venom too."

A new channel for pain relief

The work "highlights the key role of sodium channel Nav1.8 in pain signalling", says Rowe. "Maybe we should be focusing on Nav1.8 as a new basis for an analgesic."

"The really interesting thing about this is that the venom does act on 1.8," says Professor Graham Nicholson of the University of Technology, Sydney, who was not involved in the study.

"Whilst people have understood that 1.8 is involved in pain transmission, as far as I'm aware, none of the pharmaceutical companies are really targeting that as a potential site for analgesic development."

"I think this shows that 1.8 can have profound effects," he says.

But he points out that the venom targets the mutated form of Nav1.8 found in the grasshopper mice and not the normal form that humans possess, so using this work to stem human pain may be some way off yet.