Recent research from McGill University, published in the journal Neurobiology of Pain, reveals that nerve injuries do far more than damage local tissue. They can quietly reshape the immune system across the entire body, with striking differences between males and females. The findings provide new insight into why chronic pain develops and why it often responds differently to treatment in men and women.
Using a mouse model, researchers examined how the immune system responds after a peripheral nerve injury. Blood analyses showed clear and long-lasting immune alterations beyond the site of injury. In male mice, inflammatory markers in the bloodstream rose significantly and remained elevated over time, indicating a sustained systemic inflammatory response. In contrast, female mice did not show the same increase in classical inflammatory markers.
Despite these differences, an unexpected result emerged. When blood from injured males or females was transferred into healthy mice, it increased pain sensitivity in both cases. This suggests that nerve injuries release circulating factors capable of spreading pain signals throughout the body, even when traditional inflammation is not detectable. Importantly, the pain inducing mechanisms appear to differ by sex, pointing to previously unknown biological pathways, particularly in females.
According to the researchers, these hidden immune changes may help explain why some patients develop chronic pain long after an injury appears to have healed. The study also raises broader health concerns, as prolonged immune disruption could contribute to related conditions such as anxiety and depression.
The authors emphasize that nerve injury should be recognized as a whole-body condition rather than a localized problem. Current pain treatments often rely on generalized approaches, but these findings suggest that sex specific therapies may be necessary for more effective management of chronic pain. Understanding distinct immune pathways could support the development of personalized interventions that target the underlying causes of pain rather than only its symptoms.