Sex Bias Persists in Pain Research
/By Pat Anson, PNN Editor
It’s long been known that women are more likely than men to have chronic pain conditions such as fibromyalgia, rheumatoid arthritis, irritable bowel syndrome (IBS) and migraine. Women are also more likely to feel more severe, recurring and longer lasting pain.
Why then are women less likely to receive pain treatment? And why are some treatments less effective for women?
One obvious reason is that men and women have different biology and process pain differently. Another is a “blind spot” in pain research, which is more focused on studying males than females, according to a new review published in the journal Nature Reviews Neuroscience.
"The pain literature is biased such that, because of the overwhelming use of male animals in experiments, we are increasingly learning about the biology of pain in males. And wrongly concluding that this is the biology of pain. It's only the biology of pain in males," says author Jeffrey Mogil, PhD, a Professor of Psychology and Anesthesia at McGill University in Montreal.
Mogil reviewed over 1,000 research articles published in the journal Pain between 2015 and 2019, and found a distinct change in the sex of laboratory animals used in research. In 2015, for example, 80 percent of the studies only used male rodents. By 2019, half of studies were male-only.
SOURCE: Nature Reviews Neuroscience.
The trend towards using both male and female animals may sound like a promising change in research design. But when Mogil looked more closely at sex differences in pain literature, he found clear evidence that a male bias still exists in pain research.
"The very ideas we come up with for experiments, are based on experiments in males and therefore they work in males and not in females,” says Mogil.
Even in studies that included both male and female rodents, Mogil found that the research was often geared toward the males’ response. In experiments that “worked out” -- meaning the scientific hypothesis being tested was found to be true -- over 72% of the male rodents had a positive response, while only about 28% of the female rodents did. That strongly suggests the research was biased even before the experiments began.
"If there were no bias in the literature and there were a number of papers where the experiment worked in one sex and not the other, it should work in females just as often as in males,” explained Mogil. “Why has this happened? Because the hypothesis that that experiment tested out was generated based on prior data from experiments on only males. So, of course, it only worked in males."
The bias in research can have lasting effects on pain treatment and may help explain why some analgesic medications are more effective when taken by men.
"This research suggests that lots of what's in the pipeline right now, if it works in anyone at all, will largely be men. Whereas the clear majority of chronic pain patients have been and continue to be women," Mogil said.
Steps have been taken to reduce bias in pain research. If they want to get government funding, researchers in the United States, Canada and several European countries are now required to evaluate both sexes in their research. Mogil is optimistic those policies will eventually make a difference, but it may take awhile to undo decades of research that focused primarily on male animals.
“Performing biomedical experiments in both sexes is not only the ethically correct thing to do but also the scientifically correct thing to do, especially if we wish to reverse the particularly unimpressive track record of clinical trial success in the past few decades,” Mogil wrote.
