Researchers at the University of Colorado Boulder have identified a previously understudied brain circuit that plays a crucial role in transforming short-term pain into chronic pain that can persist for months or even years.
The findings, based on an animal study published in the Journal of Neuroscience, suggest that targeting this pathway could help prevent chronic pain or even stop it once it has begun.
The study focuses on a neural pathway known as the caudal granular insular cortex (CGIC), a small cluster of neurons located deep within the brain’s insula. According to the researchers, silencing this circuit prevented chronic pain from developing in laboratory animals and significantly reduced pain in those already suffering from long-term symptoms.
“Our research used state-of-the-art techniques to identify a specific brain circuit that essentially decides whether pain becomes chronic,” said Linda Watkins, senior author of the study and a distinguished professor of behavioral neuroscience at the University of Colorado Boulder. “When this decision-making circuit is shut down, chronic pain does not occur. If pain is already present, it fades away.”
Chronic pain affects about one in four adults, according to the US Centers for Disease Control and Prevention, with nearly one in 10 reporting that it interferes with daily life and work. Many patients with nerve-related pain experience allodynia, a condition in which even light touch is perceived as painful.
Unlike acute pain, which serves as a short-term warning signal after injury, chronic pain persists long after the initial damage has healed. Scientists have long struggled to understand why pain sometimes fails to resolve and instead becomes a lasting condition.
Previous research had hinted at the CGIC’s involvement in pain sensitivity, and studies in humans have shown that this brain region is often overactive in chronic pain patients. Until now, however, scientists lacked precise tools to manipulate this area without invasive methods.
In the new study, researchers used advanced imaging and chemogenetic techniques to track and control specific neurons in rats following nerve injury. They discovered that while the CGIC has little involvement in acute pain, it plays a central role in maintaining chronic pain by signaling the brain’s pain-processing center, which then instructs the spinal cord to continue sending pain signals.
When researchers disabled this pathway immediately after injury, pain was short-lived. In animals already experiencing chronic pain, shutting down the circuit caused the pain to subside.
First author Jayson Ball, who conducted the research as part of his doctoral work and now works in the brain-machine interface field, said the findings mark an important step forward in understanding chronic pain. He noted that advances in neuroscience are allowing researchers to identify highly specific targets for new treatments.
While the findings are preliminary and more research is needed before human applications are possible, the study raises hope for future therapies that could treat pain by directly targeting brain circuits. Such approaches could offer safer alternatives to opioids, including precision drug infusions or brain-machine interfaces designed to regulate pain-related neural activity.
The researchers say the discovery underscores how rapidly neuroscience is advancing and how close science may be to developing more effective and less addictive treatments for chronic pain.
