Public health experts estimate that up to 10 percent of adults are newly diagnosed with chronic pain, or ongoing pain that lasts longer than three to six months, each year. Chronic pain can severely diminish patients’ quality of life, contributing to mental health struggles, drug dependency, and mortality. But new research from the University of Colorado Boulder points to a potential solution: a little-known brain circuit that could serve as an “off switch.” The research, which was conducted in animals and published in the Journal of Neuroscience, suggests that this “switch” could stop chronic pain once it has begun, or even prevent it entirely.
Understudied Brain Region Could Eliminate Chronic Pain
Anyone who’s ever stubbed a toe knows the feeling of short-term, or acute, pain. This kind of pain often indicates an injury: for example, a sprained or broken toe from a run-in with heavy furniture. Long-term pain, however, persists even after the initial injury heals.
There are several potential causes of chronic pain, which can last for weeks, months, or even years. As the body’s pain response is a core part of the nervous system, many cases of chronic pain are also linked to this system. One example is allodynia, which the research team described as “an enduring symptom of neuropathic pain.” To explore allodynia and, ideally, stop it, the team assessed a tiny, seldom-studied region of the brain: the caudal granular insular cortex (CGIC).
Mapping Chronic Pain Pathways
The research was built on previous work from the lab of senior author Linda Watkins.
One 2011 study from Watkins’s lab identified the CGIC, a tiny cluster of cells roughly the size of a sugar cube, as being an important factor in mitigating ongoing pain in rats with sciatic nerve injuries. For the newly published study, researchers continued to spotlight rats with sciatic nerve injuries. This time, the team used fluorescent proteins to track which nerve cells became active after a rat experienced the injury. They found that the CGIC sends signals to the somatosensory cortex, the part of the brain that processes touch and pain. The cortex then communicates with the spinal cord, which continues transmitting pain signals after injury.
“We found that activating this pathway excites the part of the spinal cord that relays touch and pain to the brain, causing touch to now be perceived as pain as well,” said first author Jayson Ball in a University of Colorado Boulder press release.
So, why not simply remove the CGIC? The CGIC is nestled inside the folds of the human brain, and removing it is “an impractical approach for human treatments,” the press release explains. What if, then, researchers could simply shut it down instead of removing it entirely?
“Switching Off” Chronic Pain Signals
The team ultimately achieved two landmark outcomes. First, they used advanced chemogenetic (DREADD) excitation and inhibition of the CGIC to “switch” specific genes on or off within selected neurons. Second, they effectively disabled the rats’ pain circuits. When the scientists switched off the CGIC pathway shortly after injury, the animals experienced only brief pain rather than chronic pain. Notably, in cases where chronic pain had already developed, flipping the switch caused the pain to stop in its tracks. “Our research presents a clear case that specific brain pathways can be directly targeted to modulate sensory pain,” wrote first author Ball in the release.
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There are still many unknowns related to the CGIC. For example, researchers still aren’t sure what causes the CGIC to begin sending persistent pain signals. Given those unknowns, additional studies are needed before the team can apply these findings to people. However, the future looks bright. This study could pave the way for the development of new treatments such as targeted injections or infusions, which may offer safer alternatives to opioid medications for chronic pain.
“Now that we have access to tools that allow you to manipulate the brain, not based just on a general region but on specific sub-populations of cells, the quest for new treatments is moving much faster,” Ball noted in the release.
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