Males and females process pain using different cells, a new study with mice suggests.
The findings could help researchers develop the next generation of medications for chronic pain—the most prevalent health condition humans face.
“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,” says co-senior author Jeffrey Mogil, professor of pain studies at McGill University and director of the Alan Edwards Centre for Research on Pain.
“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.”
Mogil and colleagues looked at the longstanding theory that pain is transmitted from the site of injury or inflammation through the nervous system using an immune system cell called microglia and discovered it is only true in males. Interfering with the function of microglia in a variety of different ways effectively blocked pain in male mice, but had no effect in females.
T cells, a completely different type of immune cell, appear to be responsible for sounding the pain alarm in female mice. However, 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,” says co-senior author Michael Salter, a professor at the University of Toronto.
“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 as there is increased attention to the inclusion of female animals and cells in preclinical research. The US National Institutes of Health recently unveiled a new policy, similar to one already in place in Canada, to require the use of female animals and cell lines in preclinical research.
“For the past 15 years scientists have thought that microglia controlled the volume knob on pain, but this conclusion was based on research using almost exclusively male mice,” Mogil says. “This finding is a perfect example of why this policy, and very carefully designed research, is essential if the benefits of basic science are to serve everyone.”
The Canadian Institutes of Health Research, the Louise and Alan Edwards Foundation, the US National Institutes of Health, and SickKids Foundation funded the work. Researchers from Duke University also contributed. The findings appears in the journal Nature Neuroscience.
Source: McGill University