Hormone-Regulated Immune Cells Explain Why Chronic Pain Lasts Longer in Women

Chronic pain lasts longer for women than men, and new research suggests differences in hormone-regulated immune cells, called monocytes, may help explain why. In a new paper in Science Immunology, researchers at Michigan State University found a subset of monocytes release a molecule to switch off pain. These cells are more active in males due to higher levels of sex hormones such as testosterone.

Females experienced longer-lasting pain and delayed recovery because their monocytes were less active. Geoffroy Laumet, MSU associate professor of physiology, and Jaewon Sim, a former graduate student in his lab, discovered the same pattern in both mouse models and human patients.

The research involved 245 participants who had experienced traumatic injuries, mostly in car accidents, who rated their pain levels over 84 days. While the men and women in the group reported roughly the same levels of pain on the day the injury happened, as a whole, the men's cohort started feeling better much faster than the women's.

Researchers compared those pain rankings to the participants' bloodwork, which showed the men had notably higher levels of interleukin-10. IL-10 is an anti-inflammatory immune signaling protein that essentially tells the brain to switch off the pain signals it's sending out. Testosterone increases the production of IL-10 in the body.

Laumet's team was researching a small pilot project when they noticed higher levels of IL-10 in males. When the second test again showed higher levels of the substance that signals to neurons to shut down pain, they realized they were onto something. The lab used a sophisticated technique called high-dimensional spectral flow cytometry and learned that monocytes, long thought to be precursor cells without much of a function, play an essential and direct role in communicating with pain-sensing neurons by producing IL-10.

Laumet's team found that IL-10-producing monocytes were much more active in males than females. When they blocked male sex hormones, they received the opposite result. The team performed at least five types of tests on mouse models to make sure what they saw wasn't an anomaly. Each time, the results were the same.

Laumet then reached out to Sarah Linnsteadt, a colleague at University of North Carolina at Chapel Hill who was studying the psychological outcomes of people in car accidents. Her research showed a similar pattern—men had more active IL-10-producing monocytes and resolved pain faster.

"The difference in pain between men and women has a biological basis," Laumet said. "It's not in your head, and you're not soft. It's in your immune system." The study shows that pain resolution is not a passive process but an active, immune-driven one.

Roughly 70% of patients impacted by chronic pain are women, while 80% of studies done on chronic pain involve only male participants or male rats. Doctors still rely on patients rating their pain on a scale of one to 10. The problem is everyone experiences pain differently. So, when more women than men complain of long-lasting or chronic pain, the difference is often chalked up to perception or reporting.

These findings, funded by the National Institutes of Health and the Department of Defense, could mean those immune cells can be manipulated into producing more signals to calm pain. While a new treatment is likely decades away, Laumet hopes this research could one day help millions of people experience relief with non-opioid treatments and ensure women's pain is taken seriously.

This new evidence illuminates the immune–neural pain resolution pathway, shifting the thinking from how pain starts to why pain persists. The next step is to investigate how treatments could target this pathway and boost IL-10 production. These treatments could help pain resolve faster instead of just blocking pain signals. "This opens new avenues for non-opioid therapies aimed at preventing chronic pain before it's established," Laumet said.