NEWS
NORMAN, Okla. – As many people struggle with chronic pain and seek relief, opioid misuse has also risen as a serious pain-related issue. To address physical suffering while preventing addictive outcomes, University of Oklahoma researcher Ashlee Rowe is advancing biotherapeutics by studying how certain species of mice are able to resist pain from venomous scorpions.
An associate professor of biology in OU’s School of Biological Sciences, Rowe received a seed grant for the project in 2024 through the U.S. National Science Foundation’s (NSF) Accelerating Research Translation Program. The two-year funding supports two upcoming research papers, which are the basis of a patent application that could turn her findings into clinical pain therapeutics.
Rowe is a comparative neurobiologist studying how non-human animals’ nervous systems compare with the human nervous system. Her NSF-funded project focuses on small but highly venomous Arizona bark scorpions and the grasshopper mice that prey on them, two animals she has studied extensively.
The scorpions’ venom contains peptides, or little proteins, that typically activate voltage-gated sodium channels in nervous systems, leading to pain sensations. However, grasshopper mice don’t experience this pain. Past research from Rowe’s lab has shown that these mice’s nervous systems are taking additional peptides from the venom and binding them to other voltage-gated sodium channels downstream in the pain pathway, blocking the pain signals.
“As it turns out, where this peptide is binding on the sodium channel to turn it off and block pain in mice is largely the same as in a human,” Rowe said. “So, it theoretically could do the same thing in a human.”
Another unique quality of this binding mechanism is that it doesn’t take place in the central nervous system. This relationship is therefore nonaddictive in nature, providing a highly valuable solution to pain management.
Armed with this knowledge, Rowe’s lab has been working to understand how the peptide fully interacts with the sodium channel – one of the three binding sites on it is different between the mice and humans – and using computational structural modeling to redesign the peptide. That research includes utilizing the artificial intelligence-driven technology AlphaFold to visualize the interaction, followed by gene modification to develop altered peptides that can bind to all three sites in humans.
While Rowe is still preparing to test the different peptide variants that she and her team designed, the university has filed a patent application to protect her findings. She has also applied for an NIH grant that supports early-stage peptide research aimed at developing therapeutics for neurological disorders, including pain disorders.
“The NIH grant, if awarded, would provide the funding to conduct early-stage in vitro testing to identify lead therapeutic candidates,” Rowe said. “The testing pipeline could scale up from there and transition to rodent models of pain. Our testing pipeline includes a whole series of experiments that we would conduct to get lead peptide candidates to clinical trials.”
She added that her research aims to fill a critical void in health treatment. People experiencing chronic pain – which refers to ongoing or recurrent pain lasting more than 3 months – have had limited relief options. Over-the-counter drugs can cause harmful side effects when taken long term, while opioids have unpleasant side effects and are now highly regulated following increased scrutiny over their addictive qualities.
"Between 22 and 25 percent of adults in the U.S. suffer from some form of chronic pain,” Rowe said. “Often, it’s due to some type of inflammatory disease, aging-related diseases, or diseases like cancer and diabetes. For example, a portion of individuals that have diabetes suffer from pain related to diabetic peripheral neuropathy. There’s a real need for effective, non-addictive therapeutics.”
About the University of Oklahoma
Founded in 1890, the University of Oklahoma is a public research university located in Norman, Oklahoma. As the state’s flagship university, OU serves the educational, cultural, economic and healthcare needs of the state, region and nation. For more information about the university, visit www.ou.edu.
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