A ‘switch’ that turns off the pain? Closer to therapy

A preclinical study has discovered a new gene therapy that attacks pain centers in the brain and at the same time eliminates the risk of addiction to narcotic treatments, a breakthrough that could bring hope to the millions of people living with chronic pain.

Deal with it chronic pain It can be like listening to a radio with the volume turned up, and no matter what you do, the noise never seems to subside. Opioids, such as morphine, work by turning down the volume, but they also affect other parts of the brain, sometimes causing dangerous side effects or even addiction.

Potential new gene therapy is similar to a volume knob that only reduces the season of pain and leaves everything else intact, according to research by teams at the Perelman School of Medicine and Nursing School University of Pennsylvania (United States), together with collaborators from the Carnegie Mellon University and the Stanford Universitypublished in the magazine ‘Nature’.

“The goal was to reduce pain and, at the same time, reduce or eliminate the risk of addiction and dangerous side effects,” explains the doctor Gregory Corder co-senior author and associate 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 to people whose lives are disrupted by chronic pain.”

The morphine It is a narcotic derived from opium with a high potential for abuse, since patients who consume it can develop tolerance, requiring increasingly higher doses to achieve the same pain reduction.

By imaging brain cells that act as pain trackers, the team uncovered new insights into how morphine relieves suffering.

From there, they built a mouse model behavioral platform powered by artificial intelligence which tracks natural behaviors, creates a reading of pain levels and helps measure how much treatment is needed to relieve pain.

This readout, used as a kind of map, allowed the team to design a targeted gene therapy that mimics the beneficial effects of morphine but avoids the addictive ones, while providing a specific “off switch” for brain pain. When activated, this switch provides long-lasting pain relief without affecting normal sensitivity or activating reward pathways that can lead to addiction.

“As far as we know, this represents the world’s first gene therapy directed at the central nervous system for pain and a concrete model for a non-addictive and circuit-specific pain medicine,” highlights Corder.

Relieve pain without causing another problem

The results are the culmination of more than six years of research driven by a National Institutes of Health New Innovator Award which allowed Corder and his colleagues to investigate the mechanisms of chronic pain.

In 2019, 600,000 deaths were attributed to drug use, 80% of which were related to opioids. Nearly half of Philadelphians who responded to a 2025 Pew survey reported knowing someone with opioid use disorder (OUD). A third knew someone who had died from an overdose.

Chronic pain, known by some as a ‘silent epidemic,’ affects approximately 50 million Americans, costing more than $635 million annually in direct medical expenses and indirect costs from lost productivity, including missed work and reduced earning capacity. Now, these findings have the potential to help ease that pain—or, silence the noise—in some cases, if the science is confirmed by additional testing and clinical trials.

The team is moving forward with Michael Platt, James S. Riepe University Professor, Professor of Neuroscience, Professor of Psychology, in the next phase of work as a hopeful bridge to future clinical trials.

“The path from discovery to implementation is long, and this represents an important first step,” said Platt. “As a scientist and family member of people affected by chronic pain, the potential to alleviate suffering without exacerbating the opioid crisis is exciting.”