There are people who keep complaining of pain even though they have no injuries. These are chronic pain patients who feel excessive pain because the nervous system changes even after wounds heal. A gene therapy that fundamentally blocks chronic pain, which affects about one in five adults, has been developed. If commercialized, it is expected to greatly improve quality of life without opioid painkillers that have severe side effects.
A team led by Gregory Corder, a psychiatry professor at the University of Pennsylvania Perelman School of Medicine, said on the 8th in the international journal Nature that it confirmed in animal experiments "the efficacy of a new gene therapy that targets the brain's pain center while eliminating the addiction risk of opioid pain treatment." Researchers from the Perelman School of Medicine and the School of Nursing at the University of Pennsylvania, Carnegie Mellon University, and Stanford University took part in the study.
According to the team, chronic pain affects about 50 million people in the United States and causes an annual economic loss of $635 million (about 924.4 billion won) when combining direct medical expense and indirect costs such as reduced income. If a treatment emerges, it could not only prevent such losses but also become a goose that lays golden eggs. According to the global market research firm Coherent Market Insights, the global chronic pain market is expected to grow from $72.1 billion (104.7252 trillion won) in 2024 to $115.51 billion (167.1512 trillion won) in 2031.
◇ Identifying pain circuits with AI, solving with gene therapy
The team first developed a method to assess the degree of chronic pain in mice and to verify treatment effects. They deliberately damaged mouse nerves so that the animals would feel chronic pain even without wounds. Then the mice's heads or tails moved unnaturally. The team filmed this with cameras and trained artificial intelligence (AI) on the video data to identify behavioral patterns of chronic pain.
The team separated pain into sensation and suffering. The goal was to preserve normal sensation—feeling pain when injured—while removing only the unpleasant suffering such as chronic pain that occurs even when there is no problem. The unpleasantness of chronic pain arises in the brain's anterior cingulate cortex (ACC). Morphine binds to receptors on the nerve cells there. That is the mu-opioid receptor, MOR.
The team put a gene that synthesizes a receptor similar to MOR into a harmless virus and delivered it to anterior cingulate cortex nerve cells. The therapeutic gene remains inactive under normal conditions and produces receptors only when a specific drug is introduced. Such receptors are called DREADD, an English acronym meaning they are activated by specific drug signals. When they administered the signaling drug, the therapeutic gene produced the DREADD receptor and suppressed the nerve cells that cause chronic pain. The mice no longer showed the movements seen when they felt chronic pain.
Monique Smith, a professor at the University of California, San Diego (UCSD), said in an accompanying commentary in Nature that "this study is an innovative strategy that can implement experimental insights in the clinic," noting that it "suggests a safe treatment path with low addiction risk by selectively modulating only the painful emotion while preserving the sensory function of feeling pain."
◇ No involvement of morphine receptors, blocking concerns over side effects
Chronic pain is like listening to a radio with the volume stuck at maximum. When you get hurt, you naturally feel pain, but people with chronic pain keep complaining of pain even after wounds heal. The volume control does not work. At such times, synthetic opioid painkillers such as morphine, which have opium-like components, are used to turn down the pain volume.
The problem is that opioid painkillers can lead to bigger illnesses. As tolerance to opioids builds and doses increase, addiction becomes more likely, and stopping the drugs causes withdrawal symptoms such as anxiety or depression. In 2022 in the United States, nearly 110,000 people died from drug misuse, and 76% of those deaths were caused by synthetic opioid painkillers such as morphine.
Corder said, "The goal of this study was to relieve pain while eliminating the risks of painkiller addiction and side effects," adding, "By targeting the brain circuits on which the opioid painkiller morphine acts, it will offer a new path for treating chronic pain."
The therapy developed this time does not touch the receptors to which morphine binds, so there is no concern about opioid addiction or side effects. Instead, it delivered a gene to make a similar receptor to prevent nerve cells from running amok. The team said chronic pain disappears and, when administration of the signaling drug stops, the therapeutic gene also stops working, making it unlikely to cause problems like morphine.
The team said it would continue the research needed to enter human clinical trials. Experts projected that if gene therapy is combined with brain modulation technologies that do not damage tissue, such as ultrasound stimulation, "smart analgesic treatment" without opioid concerns could be possible in clinical settings.
References
Nature(2026), DOI: https://doi.org/10.1038/s41586-025-09908-w
Nature(2026), DOI: https://doi.org/10.1038/d41586-025-03987-5