How a Past Injury Can Lead to Lasting Changes in Stress and Pain Responses

A healed wound may leave behind more than just a visible scar—it can inscribe a long-term imprint on the brain's response to stress, pain, and fear. Recent research published in Current Biology reveals that previous injuries can sensitize the nervous system, causing individuals to overreact to stressors even long after physical healing. This phenomenon provides insight into how trauma and injuries early in life may contribute to chronic pain conditions, where the nervous system remains hyperresponsive.

In studies conducted at the University of Toronto Mississauga, scientists observed that mice with a history of injury exhibited heightened reactions to predator scents, representing extreme stress. These mice responded with exaggerated fear behaviors and developed persistent pain in their hind paws, affecting both the injured and uninjured sides. Remarkably, these symptoms persisted for more than six months post-injury, suggesting profound and enduring neuroplastic changes.

Dr. Loren Martin, the lead researcher, explained that the brain’s protective mechanisms can sometimes remain active unnecessarily, leading to increased sensitivity to threats over time. This maladaptive wiring may underpin chronic pain and anxiety disorders, where the brain’s threat detection remains overly vigilant.

A key discovery of the study was the role of the stress hormone corticosterone and its interaction with a protein called TRPA1—often termed the "wasabi" receptor due to its involvement in burning sensations. The research team found that corticosterone’s interaction with TRPA1 amplifies sensitivity to threats, maintaining a state of heightened alertness. Interestingly, while both stress hormones and TRPA1 were necessary for the exaggerated fear response, the prolonged pain response was driven solely by stress signaling. This suggests distinct but interconnected pathways regulate fear and pain responses.

Furthermore, blocking corticosterone signaling or inhibiting TRPA1 could reverse these exaggerated reactions, opening new avenues for treatments of stress-related chronic pain, PTSD, and other disorders associated with pain hypersensitivity. The findings highlight the importance of understanding how trauma rewires neural circuits, potentially leading to innovative therapies targeting these molecular mechanisms.

This research underscores that injury and stress can have lasting effects on the nervous system, emphasizing the need for strategies to prevent or reverse these changes. Recognizing the biological basis of stress and pain sensitivity may help develop better interventions for patients suffering from long-term pain and anxiety conditions.

Source: https://medicalxpress.com/news/2025-07-triggered-brain-rewrites-stress-responses.html