Women Experience Longer Lasting Pain Than Men and Scientists Think They Finally Know the Reason Why

New study links testosterone-tuned monocytes to an anti-pain signal after injury.

In the weeks after an accident or surgery, recovery does not look the same for everyone. Many studies have found that women, on average, experience pain that lasts longer than men’s.

Scientists have debated the reasons for years. A new study suggests part of the answer lies in the immune system, where certain cells help the body actively switch pain off.

“What we show is, it’s a real biological mechanism from the immune cells. It’s not in the mind,” Geoffroy Laumet, a physiologist at Michigan State University and an author of the new paper, told NBC News.

An Immune Off-Switch

Pain is not just a nerve signal. After an injury, immune cells move into damaged tissue and release signals that can increase pain or help calm it down. These signals influence how strongly the nervous system continues to respond.

Previous studies have suggested that males and females may rely on different immune pathways to process pain.

In a new study, published in Science Immunology, Laumet and colleagues focus on a particular immune “brake”: a molecule called interleukin-10, or IL-10, known for its ability to calm inflammation. In their experiments, IL-10 appeared to dampen pain signals by acting on receptors on sensory neurons.

The team used mice with inflammation in the skin of their paws, created with a standard lab trigger called complete Freund’s adjuvant. Male mice began to recover faster than females about a week after the inflammation began. The difference was not due to reduced inflammation in males. Instead, their inflamed tissue contained more immune cells producing IL-10.

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Most of the IL-10 came from monocytes, a type of white blood cell. At the injury site, these cells released the molecule, and nearby pain-sensing nerves had receptors that could detect it. When researchers blocked IL-10 from the monocytes, or removed the receptor from the nerves, the pain lasted longer in both male and female mice.

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The next question was obvious: why did males have more of these cells? Experiments point to hormones such as testosterone. When the researchers gave female mice a potent synthetic androgen (testosterone-like hormone), the females produced more IL-10–positive monocytes and recovered faster. When they removed testosterone sources from males or blocked androgen signaling, males lost that advantage.

Toward Better Pain Care

To see whether the pattern held up in people, the researchers examined data from the AURORA study, which follows patients after traumatic injuries such as car accidents in the U.S. At the time of injury, men and women reported similar levels of pain. In the following months, however, pain levels declined faster in men. Researchers also found higher levels of IL-10 in blood samples from men, and those higher levels predicted lower pain later in recovery.

But no single pathway explains every chronic pain condition. “Does it explain everything? I don’t think so. We don’t have any single, magical pathway,” Michele Curatolo, a pain specialist at the University of Washington who was not involved in the study.

Still, the work lands in a tense social context. Chronic pain affects huge numbers of people in the United States, and women are overrepresented in many chronic pain disorders. When women describe pain, they often meet skepticism—at home, at work, and in clinics.

“A lot of women are taught to hide their pain, because then, if they don’t, people will perceive that they can’t do their jobs, that they can’t take care of their families,” Ann Gregus, a chronic pain researcher at Virginia Tech who was not part of the study, told NBC News.

If the immune system holds an “off-switch,” could medicine press it? In mice, a molecule called resolvin D1—one of the molecules the body uses to bring inflammation under control—boosted IL-10–positive monocytes and sped recovery in both sexes, erasing the sex gap in that model.

Laumet thinks treatments applied to the skin, such as testosterone-based patches, could potentially limit the side effects associated with hormones that circulate throughout the body.

For many women, these findings may be vindicating. “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.”