A new study from the University of Colorado Boulder points to a little-known brain circuit that determines whether short-term pain goes away or becomes a long-term problem. The findings suggest that this pathway plays an important role in converting temporary pain into chronic pain that lasts months or even years.
The study, conducted on animals and published in the Journal of Neuroscience, focused on an area called the caudal granulo-insular cortex (CGIC). Researchers have found that shutting down this circuit can prevent the onset of chronic pain and stop pain that has already started.
“Our paper used a variety of cutting-edge methods to define specific brain circuits that are important for determining whether pain becomes chronic and instructing the spinal cord to carry out its instructions,” said lead author Linda Watkins, distinguished professor of behavioral neuroscience in the College of Arts and Sciences. “If this key decision maker stays silent, chronic pain won’t occur. If it’s already going on, chronic pain will go away.”
New tools fueling a “neuroscience gold rush”
This study was conducted at a time when brain research is rapidly advancing. Lead author Jason Ball describes the current moment as a “neuroscience gold rush,” driven by advanced tools that allow scientists to precisely control specific groups of brain cells.
These techniques have enabled researchers to pinpoint the neural pathways involved in complex conditions such as chronic pain. This level of detail could help guide the development of new treatments, such as targeted injections and brain-machine interfaces, that may provide safer alternatives to opioid drugs.
“This study adds an important leaf to the tree of knowledge about chronic pain,” Ball said. Ball completed his PhD in Watkins’ lab in May and now works at Neuralink, a California-based startup developing brain-machine interfaces for human health.
When pain signals are not blocked
Chronic pain is a widespread problem. About 1 in 4 adults experience the condition, and nearly 1 in 10 say it interferes with their daily lives, according to the Centers for Disease Control and Prevention.
A common feature of nerve-related pain is allodynia, a condition where even light touch causes pain.
Short-term pain and long-term pain behave very differently. Acute pain acts as a warning signal and begins when injured tissue, such as a stubbed toe, sends a message to the brain via the spinal cord. However, chronic pain continues even after the injury has healed, creating a type of false alarm that can last for weeks, months, or even years.
“Why and how people don’t get rid of their pain and end up suffering from chronic pain are big questions that continue to be answered,” Watkins said.
Targeting brain pathways that sustain pain
Early research from Watkins’ lab in 2011 pointed to the CGIC as playing an important role in pain sensitivity. This tiny region, about the size of a sugar cube, is located deep in the insula, a part of the brain involved in sensory processing. Studies in people have shown that this area tends to be overactive in people with chronic pain.
Until recently, this area was difficult to study in detail because the only way to affect it was to remove it, which was not a realistic treatment option.
In the new study, the research team used fluorescent proteins to track which nerve cells became activated after rats experienced sciatic nerve injury. They then applied advanced “chemical genetics” techniques to switch specific genes on or off within the selected neurons.
Their results showed that CGIC is not very important for managing immediate pain, but is essential for sustaining pain over the long term.
How does the brain sustain pain?
The researchers found that CGIC sends signals to the somatosensory cortex, the part of the brain that processes touch and pain. This area communicates with the spinal cord and effectively tells it to continue sending pain signals.
“We found that activating this pathway excites the part of the spinal cord that transmits touch and pain to the brain, so that touch is also perceived as pain,” Ball said.
When scientists blocked this pathway immediately after injury, the animals felt only a short period of pain. If chronic pain was already occurring, disabling the circuit stopped the pain.
“Our study makes a clear case that specific brain pathways can be directly targeted to modulate sensory pain,” Ball said.
Toward new treatments for chronic pain
Researchers still don’t know what triggers CGICs to start sending persistent pain signals, and more research is needed to translate these findings to humans.
Still, this study suggests new possibilities for treatment. Ball envisions a future where doctors can use targeted injections or infusions to affect specific brain cells without the widespread side effects and risk of addiction associated with opioids. He also suggests that brain-machine interfaces, whether implanted or externally worn, could help manage severe chronic pain.
“The search for new treatments is moving much faster now that we have access to tools that can manipulate the brain based on specific subpopulations of cells, rather than just general areas,” he said.
