Study reveals how old wounds increase sensitivity to stress

A wound can leave a lasting imprint - even after it has healed. A new study in Current Biology finds that past injuries can quietly prime the body to overreact and be more sensitive to stress, pain and fear long after the damage is gone.

These findings may help explain how early injuries or trauma can set the stage for chronic pain conditions, where the nervous system remains hypersensitive long after the initial damage has healed. can set the stage for chronic pain conditions, where the nervous system remains hypersensitive long after the initial damage has healed. 

Researchers at the University of Toronto Mississauga discovered that mice with a history of injury responded more intensely to the scent of a predator, an extremely stressful event for mice. These mice showed exaggerated fear and developed long-lasting pain in both hind paws, including the uninjured side. Strikingly, the symptoms lasted more than six months, long after the original injury had physically healed. 

"Our brains are wired to protect us - especially from threatening situations. But sometimes that protective system stays switched on - leaving us overly sensitive to stress or pain, even when the threat is long gone. Our research gives us new insight into how past injuries can shape the brain's response to future challenges, and could open the door to better treatments for chronic pain and anxiety disorders."

Dr. Loren Martin, Study Senior Author and Associate Psychology Professor, University of Toronto

First author Jennet Baumbach, a graduate student in Dr. Martin's lab, uncovered a key link between stress and lasting pain. She found that the stress hormone corticosterone interacts with a protein called TRPA1 - often called the "wasabi" receptor because it produces a distinctive burning sensation- to amplify sensitivity to future threats. This signaling loop appears to keep the nervous system primed for danger, making mice respond to predator odor with both increased fear and renewed pain, despite no new injury. 

Notably, while both TRPA1 and stress hormones like corticosterone were required for the exaggerated fear response, the long-lasting pain depended only on stress signaling, not TRPA1. This indicates that fear and pain may be driven by separate but parallel biological mechanisms. Blocking the stress hormone corticosterone or inhibiting the TRPA1 receptor could reverse these heightened responses, which opens the door to new therapeutic strategies for conditions like chronic pain, PTSD, and other stress-related disorders. 

"We're dissecting the brain and central circuits that control these behaviours," said Dr. Martin. "By understanding how trauma rewires the nervous system, we can begin to target the mechanisms that keep fear and pain locked in place."