Male and Female Immune Systems React Differently to Nerve Injury

Nerve injuries can have long-lasting effects on the immune system that appear to differ between males and females, according to preclinical research from McGill University.

Nerve injuries are common and can happen from stretching, pressure or cuts. They can have lasting consequences, including chronic pain. While the immune system typically helps repair the damaged area, a new study shows that nerve injuries can also disrupt the body’s entire immune system.

Analysis of blood samples from mice revealed signs of widespread inflammation throughout the body after a nerve injury. To the researchers’ surprise, male and female mice reacted very differently.

Males and females respond differently to nerve damage

In male mice, inflammation markers in the blood rose as expected and stayed high. But in female mice, those markers didn’t increase at all. Yet when blood from male and female mice with nerve injuries was transferred into healthy mice, it caused increased pain sensitivity in both cases. This suggests that something in the blood – though different between the sexes – spreads the pain response 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.

Broader implications

The study provides evidence that nerve injuries can have wide-reaching effects, not just tissue damage at the injury site. Long-term immune system changes may increase the risk of many chronic diseases, including chronic pain and 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.”

Reference: Zhou WBS, Shi XQ, Zhang AP, Millecamps M, Mogil JS, Zhang J. The impact of nerve injury on the immune system across the lifespan is sexually dimorphic. Neurobiol Pain. 2025;18:100195. doi: 10.1016/j.ynpai.2025.100195

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