PHILADELPHIA—A groundbreaking preclinical study has unveiled a novel gene therapy that targets pain centers in the brain without the risk of addiction associated with narcotic treatments. This breakthrough could provide much-needed relief for over 50 million Americans suffering from chronic pain.
Chronic pain can be likened to a radio with the volume stuck at maximum, an unrelenting noise that traditional opioid medications like morphine attempt to dull. However, these drugs also affect other brain areas, leading to potential side effects and addiction. The new gene therapy, developed by researchers at the University of Pennsylvania Perelman School of Medicine and School of Nursing, along with Carnegie Mellon University and Stanford University, acts like a precise volume knob, lowering the pain without touching other brain functions. The study was published today in the journal Nature.
“The goal was to reduce pain while lessening or eliminating the risk of addiction and dangerous side effects,” said Gregory Corder, PhD, co-senior author and assistant professor of Psychiatry and Neuroscience at Penn. “By targeting the precise brain circuits that morphine acts on, we believe this is a first step in offering new relief for people whose lives are upended by chronic pain.”
An AI-Driven Blueprint for Non-Addictive Pain Medicine
Morphine, a narcotic derived from opium, carries a high potential for abuse due to the development of tolerance, necessitating increasing doses for the same pain relief. The research team used brain imaging to understand how morphine alleviates pain, leading to the development of an AI-driven mouse-model behavioral platform. This platform tracks natural behaviors and provides a readout of pain levels, assisting in determining the necessary treatment intensity.
This readout served as a map for designing a targeted gene therapy that replicates morphine’s pain-relieving effects while avoiding its addictive properties. The therapy introduces an “off switch” for pain in the brain, providing lasting relief without affecting normal sensations or triggering addiction-related reward pathways.
“To our knowledge, this represents the world’s first CNS-targeted gene therapy for pain, and a concrete blueprint for non-addictive, circuit-specific pain medicine,” Corder stated.
Easing One Crisis Without Fueling Another
This discovery is the result of over six years of research, supported by a National Institutes of Health New Innovator Award. The study aims to address the dual crises of chronic pain and opioid addiction. In 2019, drug-related deaths totaled 600,000, with opioids responsible for 80% of these fatalities. A 2025 Pew survey revealed that nearly half of Philadelphians knew someone with opioid use disorder, and a third knew someone who had died from an overdose.
Chronic pain, often termed a “silent epidemic,” affects approximately 50 million Americans, incurring costs exceeding $635 million annually in direct medical expenses and indirect costs from lost productivity. These findings could potentially alleviate this burden, provided the therapy proves successful in further testing and clinical trials.
The research team, including Michael Platt, PhD, the James S. Riepe University Professor, is advancing to the next phase of work, aiming for future clinical trials.
“The journey from discovery to implementation is long, and this represents a strong first step,” Platt commented. “Speaking both as a scientist and as a family member of people affected by chronic pain, the potential to relieve suffering without fueling the opioid crisis is exciting.”
Future Prospects and Potential Impact
The implications of this research are vast, offering a potential shift in how chronic pain is managed without the risks of addiction. The work was supported by numerous grants from the National Institutes of Health and other organizations, highlighting the collaborative effort behind this scientific advancement.
Some authors have filed a provisional patent application through the University of Pennsylvania and Stanford University for the custom sequences used in developing synthetic opioid promoters. This patent underscores the innovative nature of the therapy and its potential applications.
As the research progresses, the scientific community and those affected by chronic pain will be watching closely, hopeful that this therapy could mark a new era in pain management.
