A single nerve injury can quietly reshape the immune system across the entire body.

Preclinical research from McGill University suggests that nerve injuries may lead to long-lasting changes in the immune system, and these effects appear to differ between males and females.

Nerve damage is relatively common and can result from stretching, pressure, or cuts. These injuries often cause lasting problems, including chronic pain. While the immune system usually plays a role in healing damaged tissue, new findings indicate that nerve injuries can interfere with immune activity throughout the entire body.

Blood samples taken from mice showed signs of widespread inflammation following nerve injury. Researchers were surprised to find that male and female mice responded in very different ways.

Male and Female Immune Responses Diverge

In male mice, inflammation-related markers in the blood increased and remained elevated over time. In female mice, however, those same markers did not rise. Despite this difference, blood taken from injured male or female mice caused increased pain sensitivity when transferred into healthy mice. This points to a circulating factor in the blood that spreads pain signals throughout the body, even though it appears to differ between the sexes.

“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.

Broader Health Implications

The findings suggest that nerve injuries may affect far more than the immediate area of damage. Ongoing changes in immune function could raise the risk of chronic conditions, including persistent pain as well as related issues 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.”

Reference: “The impact of nerve injury on the immune system across the lifespan is sexually dimorphic” by Wen Bo S. Zhou, Xiang Q. Shi, Alain P. Zhang, Magali Millecamps, Jeffrey S. Mogil and Ji Zhang, 20 August 2025, Neurobiology of Pain.
DOI: 10.1016/j.ynpai.2025.100195

The study was funded by the Canadian Institutes of Health Research and the Louise and Alan Edwards Foundation.

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