Why Chronic Pain Persists Longer in Women

Chronic pain endures longer in women compared to men, which a new study links to differences in monocytes, hormone-regulated immune cells that modulate pain. In a Science Immunology paper, Michigan State University researchers report finding a monocyte subset that releases interleukin-10 (IL-10) to dampen pain. These cells activate more in males, driven by higher sex hormones like testosterone.

In addition to extended pain duration, females also experience delayed healing due to less active monocytes., according to the recent findings. The research team including Geoffroy Laumet and Jaewon Sim, confirmed this across mouse models and human patients. These findings could mean those immune cells can be manipulated into producing more signals to calm pain.

“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.  

Laumet’s lab has been focused on pain for over six years. Recently, his team was researching a small pilot project when they noticed higher levels of interleukin-10, or IL-10, in males. When further tests 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.”

Using, high-dimensional spectral flow cytometry, it was determined that monocytes directly signal pain neurons through IL-10, far more robustly in males. Suppressing male hormones flipped the outcome. “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.

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.