Once Injured, Always On Edge? Investigating the Brain's Stress Response

A scar may fade, but its memory remains. According to a recent study in Current Biology, past injuries can increase sensitivity to stress, pain, and fear long after healing has occurred.

The research suggests early injuries or trauma could pave the way for chronic pain conditions by keeping the nervous system hypersensitive even when original damage is gone.

University of Toronto Mississauga researchers found mice with previous injuries displayed heightened fear response to predator scent and developed lasting pain in both hind paws, even the uninjured one. Remarkably, these effects persisted over six months post-injury healing.

"Our brains are designed to shield us from danger," explained Dr. Loren Martin, associate psychology professor and senior author of the study. "However, this protective system may stay activated, making individuals overly sensitive to stress or pain even when no threat exists. Our research sheds light on how past injuries influence brain response to future threats and could lead to better chronic pain and anxiety disorder treatments."

Jennet Baumbach, the study's first author and a graduate student in Dr. Martin's lab, discovered a key connection between stress hormones and prolonged pain. She found that corticosterone, a stress hormone, interacts with TRPA1 protein - known as the "wasabi receptor" for inducing a burning sensation - to heighten sensitivity to future threats. This loop keeps the nervous system alert, leading mice to react with increased fear and renewed pain to predator odors.

Interestingly, while both TRPA1 and stress hormones like corticosterone were necessary for heightened fear responses, only stress signaling was required for enduring pain. This suggests that fear and pain are regulated by separate but parallel biological processes. Managing the stress hormone corticosterone or inhibiting the TRPA1 receptor could reverse these amplified reactions, offering new therapeutic approaches for chronic pain, PTSD, and other stress-related disorders.

"We're studying brain circuits controlling these behaviors," said Dr. Martin. "Understanding how trauma rewires the nervous system allows us to target mechanisms that perpetuate fear and pain."