Brain Circuit Discovery Offers New Hope for Chronic Pain Treatment
Researchers have identified a brain circuit in the lateral parabrachial nucleus (lPBN) capable of suppressing pain signals, perhaps opening new avenues for chronic pain treatment. The study,led by J. Nicholas Betley, an associate professor in the Department of Biology at the University of Pennsylvania’s School of Arts & Sciences, reveals how the brain prioritizes survival needs – like hunger or fear – over pain.
The team discovered that activating neurons expressing the Y1 receptor (Y1R) within the lPBN effectively “quiets the pain signal” allowing other crucial functions to take precedence. “NPY, and NPY quiets the pain signal so that other survival needs take precedence,” explained Betley.
Interestingly, the Y1R neurons weren’t neatly organized. Rather of forming distinct groups, they were found to be “scattered across many other cell types,” according to Betley.He likened the distribution to “yellow paint distributed across red cars, blue cars, and green cars,” suggesting this mosaic pattern may allow the brain to dampen a wider range of painful inputs across multiple circuits.
This discovery has important implications for how chronic pain is understood and treated. Currently, many patients experience pain without a clear identifiable injury.Betley suggests the problem may lie within the brain circuit itself, rather than at the site of the initial injury. “If we can target these neurons, that opens up a whole new path for treatment,” he stated.
The research also highlights the potential of behavioral interventions. The study demonstrated the circuit’s “adaptability,” showing it can be “dialed up or down,” suggesting that approaches like exercise, meditation, and cognitive behavioral therapy could influence neuronal activity and pain perception. “So,the future isn’t just about designing a pill. It’s also about asking how behavior, training, and lifestyle can change the way these neurons encode pain,” Betley said.
The research team included Nitsan Goldstein (currently a postdoctoral researcher at MIT), Michelle Awh, Lavinia Boccia, Jamie R.E. Carty, Ella Cho, Morgan kindel, Kayla A. Kruger, Emily Lo, Erin L. Marble, Nicholas K. Smith, Rachael E. villari, and Albert T.M. Yeung of Penn Arts & Sciences; Niklas Blank and Christoph A. Thaiss of Penn’s Perelman School of Medicine; Melissa J. Chee and Yasmina Dumiaty of Carleton university; Rajesh Khanna of University of Florida college of Medicine; Ann Kennedy and Amadeus maes of Scripps Research Institute; and Heather N. Allen, Tyler S. Nelson and Bradley K. Taylor of the University of Pittsburg.
The study was supported by funding from the Klingenstein Foundation, the University of Pennsylvania School of Arts and Sciences, and numerous grants from the National Institutes of Health (including F31DK131870, 1P01DK119130, 1R01DK133399, and others), the National Science Foundation Graduate Research Fellowship Program, the Blavatnik Family Foundation Fellowship, the American Neuromuscular Foundation Advancement Grant, the American Heart Association, the Swiss National Science Foundation, the Canadian Institutes of Health Research, the Simons Foundation, a McKnight Foundation Scholar Award, and a pew Biomedical Scholar Award.
