Chronic pain lasts longer for women than men, and new research suggests that differences in hormone-regulated immune cells, called monocytes, may help explain why. Researchers headed by a team at Michigan State University found that a subset of monocytes releases a molecule to switch off pain. These cells, the researchers discovered, are more active in males due to higher levels of sex hormones such as testosterone.
The studies identified monocytes that produce the anti-inflammatory cytokine interleukin-10 (IL-10) as a driver of sex differences in pain resolution in mice. Research lead Geoffroy Laumet, PhD, MSU associate professor of physiology, Jaewon Sim, PhD, a former graduate student in his lab, and colleagues also found that in humans, men who suffered traumatic injury resolved pain faster than women, which was again linked to elevated levels of circulating monocytes and IL-10.
The results pinpoint an immune mechanism that could inform therapeutics for sex-biased chronic pain conditions, and could mean that 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.”
Senior author Laumet, first author Sim and colleagues reported on their findings in Science Immunology, in a paper titled “Monocyte-derived IL-10 drives sex differences in pain duration,” in which they concluded “Overall, our findings identify monocyte-derived IL-10 as a critical mediator of communication between infiltrating immune cells and sensory neurons during pain resolution.”
![Geoffroy Laumet, MSU Associate Professor of Physiology, and Sabrina De Souza, MSU postdoctoral researcher, pipette samples in Laumet’s lab. [Finn Gomez, MSU College of Natural Science]](https://www.genengnews.com/wp-content/uploads/2026/02/low-res-5-300x200.jpeg)
Pain results when neurons found throughout the 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. “Nociceptive neurons are specialized peripheral sensory neurons that detect noxious, potentially tissue-damaging stimuli and relay pain signals to the central nervous system,” the authors explained. But for those with chronic pain, these sensors may be activated with mild stimulation, or even no stimulation at all. “Chronic pain is a prevalent health issue affecting more than 100 million individuals in the United States and incurring major health care costs,” they noted.
Doctors still rely on patients rating their pain on a scale of one to 10. The problem is that everyone experiences pain differently. And, as the authors also pointed out, women frequently experience longer-lasting pain than men, which indicates that women experience delayed pain resolution. “There is a distinct female predominance in most chronic pain syndromes, likely driven by slower pain resolution in women,” the team continued, “… but the mechanisms underlying this sex difference remain unclear.”
Prior research has shown that IL-10 can suppress specialized sensory pain neurons, or nociceptors, that express the IL-10 receptor. However, it has been unclear whether IL-10 signaling also underlies sex differences in pain resolution. Laumet’s lab has been studying pain for six years. The 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.
“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.”
![Aaryn Edwards, MSU graduate student, and Geoffroy Laumet, MSU Associate Professor of Physiology, work on a sample in Laumet’s lab. [Finn Gomez, MSU College of Natural Science]](https://www.genengnews.com/wp-content/uploads/2026/02/low-res-4-300x200.jpeg)
Laumet’s lab used a sophisticated technique called high-dimensional spectral flow cytometry to investigate further in mice. They examined immune dynamics in a mouse model of inflammatory pain, and observed that male mice resolved pain faster and had higher numbers of IL-10–producing (IL-10+) monocytes in inflamed skin when compared with female mice. They learned that monocytes play an essential and direct role in communicating with pain-sensing neurons by producing IL-10.
The researchers also 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. “Male mice exhibited faster pain resolution than females, which was associated with higher numbers of IL-10+ monocytes,” they reported. Depleting these monocytes or deleting the IL-10 receptor in skin nociceptors delayed pain resolution. “Mice whose monocytes lacked IL-10 or androgen receptors (ARs) exhibited delayed pain resolution.”
To ascertain whether sex hormones play a role in this process, the team treated female mice with a form of testosterone after removing their ovaries. This resulted in elevated IL-10+ monocyte numbers and accelerated pain resolution in the females. Laumet said, “This study shows that pain resolution is not a passive process. It is an active, immune-driven one.”
The investigators performed at least five types of tests on two mouse models, including a trauma model, to make sure what they saw wasn’t an anomaly. Each time, the results were the same.
The researchers also reached out to Sarah Linnsteadt, PhD, 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 in humans—men had more active IL-10-producing-monocytes and resolved pain faster.
![These side-by-side microscope images demonstrate lower IL-10 receptor subunit levels, shown in yellow, in female skin cells (left) than in male cells (right). [Laumet lab.]](https://www.genengnews.com/wp-content/uploads/2026/02/low-res-2-1-300x169.jpeg)
The experimental results in addition determined that a lipid mediator molecule, resolvin D1 (RvD1), could speed up pain resolution by increasing IL-10+ monocytes in both male and female mice, highlighting the molecule’s therapeutic potential. “Increasing IL-10+ monocytes with RvD1 in mice alleviated pain in both sexes and eliminated sex differences, highlighting the therapeutic potential of enhancing IL-10+ monocytes for treating sex-biased pain conditions,” they stated.
The collective 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.”
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