Nerve injuries are common and can occur from stretching, pressure or cuts. They often lead to persistent problems such as chronic pain. Although the immune system normally works to repair damaged tissue, the new findings indicate that nerve injuries can also shift immune activity throughout the entire body.

Laboratory analysis of blood from mice showed clear evidence of bodywide inflammation after a nerve injury. Researchers also found that males and females did not respond in the same way.

Distinct Immune Patterns in Males and Females

In male mice, inflammatory markers in the bloodstream increased and remained elevated. In female mice, those same markers did not rise at all. Yet when blood taken from injured males or females was transferred into healthy mice, it produced increased sensitivity to pain in both cases. According to the researchers, this means that something in the bloodstream — although not the same in males and females — is capable of spreading pain responses throughout the body.

“That means whatever is causing pain in females is working through a completely different biological pathway that we don’t yet understand,” said co-author Jeffrey Mogil, E.P. Taylor Professor of Pain Studies at McGill and a Distinguished James McGill Professor.

“By understanding how men and women react differently to nerve injuries, we can work toward more personalized and effective treatments for chronic pain,” added Sam Zhou, the study’s lead author and a PhD student at McGill.

Wider Health Implications

The researchers report that nerve injuries may influence much more than the damaged site. Long-lasting disruptions to immune function could raise the likelihood of chronic pain and potentially contribute to related conditions such as anxiety and depression.

“Recognizing the full impact of nerve injuries is important for both doctors and patients,” said Dr. Ji Zhang, the senior author and a professor at McGill’s Department of Neurology and Neurosurgery and Faculty of Dental Medicine and Oral Health Sciences. “A localized nerve injury can affect whole body. Men and women may respond differently.”

“The impact of nerve injury on the immune system across the lifespan is sexually dimorphic” by Sam Zhou, Xiang Shi, Alain Zhang, Magali Millecamps, Jeffrey Mogil and Ji Zhang was published in Neurobiology of Pain. The study was funded by the Canadian Institutes of Health Research and the Louise and Alan Edwards Foundation.