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Unusual predator-prey relationship offers clues for novel approaches to pain research

Grasshopper mouse eats poisonous Arizona bark scorpion

Grasshopper mouse eats poisonous Arizona bark scorpion


INDIANAPOLIS — Grasshopper mice are cute, amazing little critters, but the big news involving them recently isn’t so much about them, or the normally painful venom of Arizona bark scorpions, which the mice readily eat despite the scorpion’s debilitating and deadly sting.

The pathbreaking findings reported in the prestigious journal Science involve two miniscule sodium channels (Nav1.7 and Nav.1.8) in pain-sensing neurons found throughout the peripheral nervous system of mice — and humans — and the potential for new directions in analgesic research.

“The study really shows that although alterations in Nav1.7 can trigger intense pain, blocking Nav1.7 is not necessary to block the pain. We now know that Nav1.8 can be effectively targeted with profound consequences,” said Ted Cummins, co-author of the study and professor of pharmacology and toxicology at the IU School of Medicine. “In grasshopper mice, the toxin is turned from pain to gain by not just reducing sensitivity, but by actually turning it into an effective analgesic.”

“This highly unusual evolutionary outcome not only provides a better understanding of the predator-prey relationships and how they are shaped over millions of years in niche environments, but also points the way to several potentially novel approaches to the development of new analgesics,” said Gerry Oxford, executive director of the Stark Neurosciences Research Institute at the IU School of Medicine.

The Cummins Lab has been studying the role of sodium channels in pain mechanisms for more than a decade at IU and has previously shown that genetic mutations that cause severe chronic pain in humans can substantially alter the activity of the Nav1.7 sodium channels.

The research for the Science article, “Voltage-gated sodium channel in grasshopper mice defends against bark scorpion toxin,” began after lead author Ashlee Rowe, assistant professor of neuroscience and zoology at Michigan State University, discovered that grasshopper mice, which are native to the southwestern U.S., generally are resistant to bark scorpion venom. While at the University of Texas at Austin, she and colleagues collected scorpions and mice for the research and enlisted the help of co-authors Cummins and Yucheng Xiao, research associate at IU School of Medicine.

Rowe told NBC News that to humans, the scorpion’s sting “feels like being burned with cigarettes, or like you’ve been branded, or like a nail being driven through your skin.” She said it can kill animals the size of the grasshopper mouse.

For the study, they injected common house mice and grasshopper mice with the scorpion venom and a neutral saline solution, which mice find painful. When injected with the venom, the house mice experienced temporary paralysis, seizures and other problems. The grasshopper mouse demonstrated none of this pain and discomfort, and the venom actually blocked the pain the grasshopper mice normally experience from saline injections.

By sequencing the genes for both the Nav1.7 and Nav1.8 sodium channels, they discovered that channel Nav1.8 in grasshopper mice contained a mutation, an amino acid that was different from mammals, such as house mice, rats and humans, that are sensitive to bark scorpion stings.

“Incredibly, there is one amino acid substitution that can totally alter the behavior of the toxin and block the channel,” co-author Harold Zakon, a neuroscience professor at UT Austin, said in a statement.

Scorpions aren’t the only toxic creature to visit the Cummins Lab. Cummins and Xiao have been studying toxins from other organisms, including tarantulas. The lab has recently collaborated with researchers at Eli Lilly and Co. investigating the role of sodium channels in several different pain syndromes, including chemotherapy-induced pain.

“Nature has spent millions of years targeting sodium channels, and understanding how biological toxins manipulate sodium channel activity and pain sensations provides great insight that hopefully can be used to help develop better strategies for treating pain,” Cummins said.

The Science study, published Oct. 25, was covered widely in the media, with reports in Nature World News, Forbes, Los Angeles Times, ABC Science, the NIH Director’s Blog and Christian Science Monitor, among others.