A new preclinical study has introduced a gene therapy that targets pain centers in the brain and aims to eliminate the risk of addiction associated with narcotic treatments. This development could impact more than 50 million Americans living with chronic pain.
Researchers from the University of Pennsylvania Perelman School of Medicine and School of Nursing, together with Carnegie Mellon University and Stanford University, published their findings in Nature. The study describes how current opioid medications, such as morphine, lower pain but can also cause dangerous side effects and addiction by affecting other parts of the brain.
Gregory Corder, PhD, co-senior author and assistant professor of Psychiatry and Neuroscience at Penn, explained: “The goal was to reduce pain while lessening or eliminating the risk of addiction and dangerous side effects. 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.”
The team used imaging techniques to observe brain cells involved in tracking pain. They then developed a mouse-model behavioral platform powered by artificial intelligence (AI) to monitor natural behaviors and assess pain levels. This approach enabled them to design a targeted gene therapy that mimics the beneficial effects of morphine without causing addiction. The therapy includes an "off switch" for pain signals in the brain, providing long-lasting relief without altering normal sensations or activating reward pathways linked to substance abuse.
Corder said: “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.”
The research is based on over six years of investigation supported by funding from organizations such as the National Institutes of Health New Innovator Award. In 2019, drug use accounted for 600,000 deaths globally, with opioids responsible for 80 percent of those fatalities. A 2025 Pew survey found that nearly half of Philadelphia residents knew someone affected by opioid use disorder; one-third knew someone who had died from an overdose. Chronic pain affects around 50 million Americans each year and results in significant economic costs due to medical expenses and lost productivity.
Michael Platt, PhD, James S. Riepe University Professor at Penn and Professor of Neuroscience and Psychology, is collaborating on advancing this work toward clinical trials. He commented: “The journey from discovery to implementation is long, and this represents a strong first step. 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.”
Funding sources for this research included several NIH grants along with support from other foundations. Some authors have filed a provisional patent application through the University of Pennsylvania and Stanford University related to synthetic opioid promoters.
