Gene Therapy Developed for Non-Addictive Chronic Pain Relief
A preclinical study has identified a new gene therapy designed to target pain centers in the brain while aiming to eliminate the risk of addiction associated with traditional narcotics treatments. This research, published in Nature, was conducted by teams at the University of Pennsylvania Perelman School of Medicine and School of Nursing, in collaboration with Carnegie Mellon University and Stanford University.
Mechanism of Action
Opioid medications, such as morphine, reduce pain by affecting multiple brain regions, which can lead to side effects and addiction. The developed gene therapy is designed to specifically target and reduce pain signals without impacting other brain functions or activating the reward pathways associated with addiction. Gregory Corder, co-senior author and assistant professor of Psychiatry and Neuroscience at Penn, stated the objective was to reduce pain while minimizing the risk of addiction and dangerous side effects.
Research Methodology
The research involved investigating how morphine alleviates suffering by imaging brain cells that track pain. Utilizing this insight, the team constructed an artificial intelligence (AI)-driven mouse model behavioral platform. This platform tracked natural behaviors to assess pain levels and determine the required treatment to alleviate pain.
This data informed the design of a targeted gene therapy that mimics morphine's pain-reducing effects but avoids its addictive properties. The therapy delivers an "off switch" specifically for pain felt in the brain, providing durable pain relief without affecting normal sensation or triggering reward pathways that can lead to addiction. Corder noted that this development represents the first central nervous system (CNS)-targeted gene therapy for pain and provides a framework for non-addictive, circuit-specific pain medicine.
Public Health Context
Chronic pain impacts approximately 50 million Americans, incurring an estimated annual cost exceeding $635 million in direct medical expenses and lost productivity. The study also addresses concerns related to the opioid crisis; in 2019, 600,000 deaths were attributed to drug use, with 80 percent related to opioids. A 2025 Pew survey indicated that nearly half of Philadelphia residents reported knowing someone with opioid use disorder (OUD), and one-third reported knowing someone who had died from an overdose.
Future Developments
The research team plans to proceed with Michael Platt, a Professor of Neuroscience and Psychology, on the next phase of work. This subsequent phase aims to facilitate the transition toward future clinical trials. Platt acknowledged the extensive process from discovery to implementation.
Funding and Intellectual Property
This work received support from the National Institutes of Health (NIGMS DP2GM140923, NIDA R00DA043609, NIDA R01DA054374, NINDS R01NS130044, NIDA R01DA056599, NIDA R21DA055846, NIDA F31DA062445, NINDS F31NS143421, NIDA F32DA053099, NIDA F32DA055458, NIDA F31DA057795, NINDS F31NS125927, NIDA T32DA028874, NINDS RF1NS126073), the Howard Hughes Medical Institute, the Whitehall Foundation, and the Tito's Love Research Fund.
Some authors are inventors on a provisional patent application filed through the University of Pennsylvania and Stanford University concerning the custom sequences and applications of synthetic opioid promoters (patent application number: 63/383,462 ‘Human and Murine Oprm1 Promoters and Uses Thereof’).