Why chronic pain lasts longer in women: Immune cells offer clues

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 reported that a subset of monocytes releases a molecule to switch off pain. These cells are more active in males due to higher levels of sex hormones such as testosterone, the team found.

Females, however, 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.

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.

“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.”

Pain results when neurons found throughout your body are activated by stimulation. Most of the time they’re silent, but they become activated when you stub your toe or fall off a bike. But for those with chronic pain, the sensors may be activated with mild stimulation or even no stimulation at all.

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 attributed to perception or reporting.

Laumet has devoted his lab to studying pain for six years. His team was researching a small pilot project when they noticed higher levels of interleukin-10, or 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 on to something.

“That was the turning point for me,” Sim said. “I feel extremely fortunate that we trusted those early, uncertain findings and chose to pursue them further.”

Laumet’s lab dove into the research using a sophisticated technique called high-dimensional spectral flow cytometry. They 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.

“This study shows that pain resolution is not a passive process,” Laumet said. “It is an active, immune-driven one.”

Laumet’s 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.

That’s when he reached out to Sarah Linnstaedt, 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.

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.

“Future researchers can build on this work,” Laumet said. “This opens new avenues for non-opioid therapies aimed at preventing chronic pain before it’s established.”