The role of biological sex in pain

According to researchers, each sex has distinct cells that appear to be involved in processing pain.

"The biological processing of pain, regardless of how much pain is produced, is dramatically sex dependent," said Jeffrey Mogil, a psychology professor at McGill University. "Different genes are being used in both sexes — different proteins, different cell types, dramatically different biology in each case."

According to a fact sheet that Mogil and other researchers wrote for the International Association for the Study of Pain, there are dozens of variables linked to pain in one sex, but not the other.

• Gene-level differences: Researchers have found that variations in genes, such as those that encode a single type of opioid receptor, have been linked to heightened pain sensitivity in females, while variations in genes that encode another type of receptor have been linked to higher thresholds for thermal and muscle pressure pain in males.
• Hormones: Researchers have found that higher estrogen levels play a major role in suppressing high levels of pain, while higher progesterone levels seem to exacerbate it. Prolactin, a hormone that produces breast milk, can increase "female-selective" sensitivity in the sensory receptors that trigger pain signals throughout the body, and testosterone seems to trigger pain in both sexes.

The role of gender

According to Diane Hoffmann, director of the University of Maryland Law School's law and healthcare program, research has found that pain is "multifactorial."

"You can't just look at the biological and physiological," she said. "You have to look at that in combination with not just the psychological, but social and cultural impacts and how they affect a person's experience of pain as well."

Studies have also found that women do more catastrophizing, or dwelling on their pain, a practice that has been associated with greater pain severity. Women are also more likely to seek out help for pain than men, Neklason reports, but when they do, providers more often dismiss, psychologize, and undertreat their pain, which could make disparities worse.

Still work to do

"We only know a fraction of the biological sex differences," Mogil said. "I mean, they're only starting to emerge now. And pain and gender is almost completely unstudied. There's only a handful of papers that have ever been done."

Experts say there's still more work to be done examining the biological and sociocultural factors that impact men and women's different experiences of pain.

According to Elizabeth Reynolds Losin, the director of Pennsylvania State University's Social and Cultural Neuroscience Lab, the sex differences in pain are undeniable.

"In animals, it seems well accepted that there are sex differences in pain physiology going from the cellular molecular level on up to the systems level," Reynolds Losin said. "In humans, I feel like it's still kind of a controversial idea that there could be sex differences in pain."

With continued doubts and questions about the efficacy and validity of research, Roger Fillingim, director of the University of Florida's Pain Research and Intervention Center of Excellence, predicts that, with growing focus on the topic of biological sex and pain, we'll have a better understanding of not only how pain is processed, but also how it's treated.

"If you look at research on sex, gender and pain over the last 30 years, it is a dramatically upward slope," Fillingim said. "There's a lot more attention to sex as a biological variable, to sex differences in pain, and now to the complexity and nuances of sex versus gender."

"I think it's conceivable," he said, "that within my lifetime, we'll see specific treatments that are developed for women versus men."