A new mouse study has demonstrated that different immune cells in male and female mice are responsible for the transmission of pain, contrary to longstanding theories on pain.
These findings may have implications for future treatment of chronic pain - the most prevalent human health condition - implying that different strategies could be required for treating men and women.
The study is published in Nature Neuroscience and was conducted by researchers from McGill University, Duke University and The Hospital for Sick Children (SickKids).
Previously, researchers had held that pain is transmitted from sites of injury or inflammation through the immune system by a cell called microglia, with a large and gradually increasing body of evidence supporting this theory.
In the US, chronic pain is incredibly prevalent. According to the National Institutes of Health (NIH), 1 in every 4 Americans has experienced chronic pain, with pain affecting more Americans than diabetes, coronary heart disease and cancer combined.
"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 Dr. Jeffrey Mogil of McGill University.
The assumption was backed by research, but this research was subject to one particular weakness - namely the gender of the mice used in previous studies.
"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," Dr. Mogil explains.
In the new study, the researchers investigated the possibility that observed differences in pain sensitization between male and female rodents could be because microglia may not be required for pain processing in female mice.
Findings highlight the importance of inclusive research practices
The researchers found that interfering with microglia function in a variety different ways served to block pain in male mice but not female mice. Instead, the researchers discovered that another type of immune cell - T cells - were likely to be responsible for pain transmission, although the researchers are still to discover precisely how.
"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," states Dr. Mogil.
Dr. Michael Salter, Head and Senior Scientist of Neuroscience & Mental Health at SickKids, says that the findings indicate there are significant questions to be asked concerning human pain drug development, on account of mice having similar nervous systems to humans.
"Understanding the pathways of pain and sex differences is absolutely essential as we design the next generation of more sophisticated, targeted pain medications," he states.
As well as affecting how the next generation of medication for chronic pain is developed, these findings could also influence future biomedical studies conducted using mice. The results indicate that male mice are unsuitable to be used as proxies for female mice.
This discovery comes while increased attention is being paid to the gender of animals and cells used in preclinical research. Recently, the NIH introduced a policy that makes the use of female animals and cells in such research mandatory in the US, following the lead of other countries such as Canada.
"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," says Dr. Mogil.