2015 Research Highlights: Sex Differences in Mechanisms Underlying Pain


Different immune cells are crucial for pain in male versus female mice, an important finding with clinical implications for patients with chronic pain. Image credit: sylverarts/123RF Stock Photo.

Chronic pain occurs more frequently in women than men, and women report higher levels of pain than men. Despite these sex differences, animal studies of pain, which are conducted to understand the basic neurobiology of pain and test potential new treatments, typically only involve male animals; this is because, in part, the need to control for hormone fluctuations in females can complicate study design. Research published online June 29 in the journal Nature Neuroscience highlighted a problem with this approach: biology sometimes differs between males and females, so studying only one sex can produce misleading conclusions. The findings also suggest that treatment of chronic pain in people may require different strategies in women vs. men.

In the study, researchers led by Jeffrey Mogil, from McGill University in Montreal, Canada, and Michael Salter, from the University of Toronto, Canada, reported that different immune cells play a crucial role in pain sensitivity in male versus female mice. The investigators severed part of the sciatic nerve in mice in order to produce elevated pain sensitivity in the animals’ hindpaws. Consistent with earlier studies demonstrating that immune cells called microglia play a role in pain sensation, administration of drugs that inhibited microglia reversed this pain hypersensitivity in male mice. However, this reversal did not occur in females, suggesting that another cell type was more important to maintain pain in female animals. Indeed, subsequent experiments showed that pain hypersensitivity in the female mice likely involved a different immune cell called the T lymphocyte.

“People are making the assumption that the biology is the same across sexes, and this study shows very radically and very clearly that this assumption can be false.”

Jeffrey Mogil, McGill University

The research adds to a growing body of evidence that underscores the importance of analyzing both sexes in pain research, and suggests that the development of pain treatments targeting the immune system may require different approaches in men versus women. “People are making the assumption that the biology is the same across sexes, and this study shows very radically and very clearly that this assumption can be false,” Mogil said. The assumption is of particular concern in pain research, considering the variation in the prevalence of various pain conditions between women and men.

In recognition of mounting sex differences between animals used in preclinical research, the National Institutes of Health (NIH) announced in May 2014 that researchers funded by NIH grants will soon be required to use both sexes in animal and cell studies. The policy is expected to take effect sometime in 2016. “The current study is a perfect example of the wisdom of the NIH policy,” said Mogil. —Allison Marin.

To read about the research in more detail, see the related Pain Research Forum news story here.

Allison Marin (Curley), PhD, is a neuroscientist-turned-science writer who resides in Pittsburgh, Pennsylvania, US.