Penn researchers, alongside researchers from the University of Pittsburgh and the Scripps Research Institute, have identified a key driver of chronic pain and, potentially, how to relieve it.
Their work, published in a study in Nature magazine, was spearheaded by Penn associate professor of Biology J. Nicholas Betley. It sought to find an indicator in the brain to potentially alleviate the effects of chronic pain.
“[Chronic pain] is not just an injury that won’t heal,” Betley said to Penn Today. “It’s a brain input that’s become sensitized and hyperactive, and determining how to quiet that input could lead to better treatments.”
The researchers experimented on mice in order to track their neurologic responses to acute and sustained pain stimuli. They found that only one subgroup of the neurons that respond to painful stimuli — classified as Y1R neurons — continue to fire invariably during lasting pain, a state known as “tonic activity.”
Crucially, when blocking the neural transmissions of this subgroup, the study revealed that the pain experienced by the mice decreased dramatically.
“There are circuits in the brain that can reduce the activity of neurons that transmit the signal of pain,” Betley said.
Betley’s research into Y1R neurons was rooted in a discovery years earlier by Betley’s lab that hunger in animals could suppress chronic pain responses.
“From my own experience, I felt that when you’re really hungry you’ll do almost anything to get food,” he said. “When it came to chronic, lingering pain, hunger seemed to be more powerful than Advil at reducing pain.”
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Although Betley’s work identified the link between hunger and dampened pain, it was 2022 Ph.D. graduate Nitsan Goldstein, a former student in Betley’s lab, who found that other survival needs had the potential to reduce pain too. She aimed to find the neurons responsible for prioritizing these survival needs over pre-existing pain.
“It’s like the brain has this built-in override switch,” Goldstein said to Penn Today. “If you’re starving or facing a predator, you can’t afford to be overwhelmed by lingering pain.”
The researchers emphasize that the findings of this study have the potential to change the landscape for drug development for chronic pain. According to the 2023 National Health Interview Survey, more than 24% of the American adult population has experienced chronic pain in the past three months.
Oftentimes, the difficulty in developing successful treatments for chronic pain is that the source is difficult to identify.
“What we’re showing is that the problem may not be in the nerves at the site of injury, but in the brain circuit itself,” Betley said. “If we can target these neurons, that opens up a whole new path for treatment.”
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Staff reporter Rachel Erhag covers student government and can be reached at rerhag@sas.upenn.edu. At Penn, she studies philosophy, politics, and economics. Follow her on X @RErhag.
