Male And Female Pain Processing Involves Different Circuits

Pain is processed in mice using different cells, depending on their gender, new research released on June 29 in Nature Neuroscience reports.

The findings have wide ranging implications for our scientists’ understanding of pain as well as how they develop the next generation of medications for chronic pain. They may also impact the way basic biomedical research using mice is conducted.

Co-senior author Jeffrey Mogil of McGill University, director of the Alan Edwards Centre for Research on Pain, said:

“Research has demonstrated that men and women have different sensitivity to pain and that more women suffer from chronic pain than men, but the assumption has always been that the wiring of how pain is processed is the same in both sexes. The realization that the biological basis for pain between men and women could be so fundamentally different raises important research and ethical questions if we want to reduce suffering.”

Teams from McGill, The Hospital for Sick Children (SickKids), and Duke University, collaborating on the research, looked at the prevalent theory that pain is transmitted from the site of injury or inflammation through the nervous system using an immune system cell called microglia.

This latest research demonstrates that the theory is only true in male mice. Interfering with the function of microglia in a variety of different ways effectively blocked pain in male mice, but had no effect in female mice.

The researchers say that a totally different type of immune cell, called T cells, seems to be responsible for setting off the pain alarm in female mice. Exactly how this happens remains unknown.

“Understanding the pathways of pain and sex differences is absolutely essential as we design the next generation of more sophisticated, targeted pain medications,” said Michael Salter, M.D., Ph.D., Head and Senior Scientist, Neuroscience & Mental Health at SickKids and Professor at The University of Toronto, the other co‑senior author. “We believe that mice have very similar nervous systems to humans, especially for a basic evolutionary function like pain, so these findings tell us there are important questions raised for human pain drug development.”

The discovery comes at a time of more attention to the importance of including female animals and cells in preclinical research. The U.S. National Institutes of Health recently unveiled a new policy, similar to one already in force in Canada, to require the use of female animals and cell lines in preclinical research.

Robert E Sorge, Josiane C S Mapplebeck, Sarah Rosen, Simon Beggs, Sarah Taves, Jessica K Alexander, Loren J Martin, Jean-Sebastien Austin, Susana G Sotocinal, Di Chen, Mu Yang, Xiang Qun Shi, Hao Huang, Nicolas J Pillon, Philip J Bilan, YuShan Tu, Amira Klip, Ru-Rong Ji, Ji Zhang, Michael W Salter and Jeffrey S Mogil
Sexual dimorphism in pain hypersensitivity
Nature Neuroscience (2015) doi:10.1038/nn.4053

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