At McGill University in Montreal, Canada, Sorge was investigating how animals develop an extreme sensitivity to touch. To test for this response, Sorge poked the paws of mice using fine hairs, ones that wouldn’t ordinarily bother them. The males behaved as the scientific literature said they would: they yanked their paws back from even the finest of threads.
But females remained stoic to Sorge’s gentle pokes and prods1. “It just didn’t work in the females,” recalls Sorge, now a behaviourist at the University of Alabama at Birmingham. “We couldn’t figure out why.” Sorge and his adviser at McGill University, pain researcher Jeffrey Mogil, would go on to determine that this kind of pain hypersensitivity results from remarkably different pathways in male and female mice, with distinct immune-cell types contributing to discomfort2.
Sorge and Mogil would never have made their discovery if they had followed the conventions of most pain researchers. By including male and female mice, they were going against the crowd. At the time, many pain scientists worried that females’ hormone cycles would complicate results. Others stuck with males because, well, that’s how things were done.
Today, inspired in part by Sorge and Mogil’s work and spurred on by funders, pain researchers are opening their eyes to the spectrum of responses across sexes. Results are starting to trickle out, and it’s clear that certain pain pathways vary considerably, with immune cells and hormones having key roles in differing responses.
This push is part of a broader movement to consider sex as an important variable in biomedical research, to ensure that studies cover the range of possibilities rather than gleaning results from a single population. A major change came in 2016, when the US National Institutes of Health (NIH) made it a requirement for grant applicants to justify their choice of the sex of animals used in experiments.
The discoveries in pain research are among the most exciting to emerge, says Cara Tannenbaum, scientific director of the Institute of Gender and Health in Montreal, part of the Canadian Institutes of Health Research. And of Sorge and Mogil’s work, she adds, “To my knowledge, no other field of science has identified this type of sex difference.
