Researchers at Michigan State University have identified a specific type of immune cell that helps explain why men tend to recover from inflammatory pain faster than women. The finding, published in Science Immunology, centers on monocytes that produce the anti-inflammatory molecule interleukin-10, or IL-10, and their direct communication with pain-sensing neurons. With about 50 million Americans living with chronic pain and women bearing a disproportionate share of that burden, the discovery opens a new line of inquiry into sex-specific treatments that could one day narrow the gap.
Male Mice Resolve Pain Faster Thanks to IL-10 Monocytes
The central finding is straightforward but striking: male mice resolve inflammatory pain more quickly than females, and the difference traces back to a single immune cell population. According to the peer‑reviewed report, males carry a higher abundance of monocytes that produce IL-10, an anti-inflammatory signaling protein. These cells communicate directly with sensory neurons at the site of injury, effectively telling the nervous system to dial down pain signals once the initial threat has passed. In males, that feedback loop appears to switch on more robustly and more quickly, shortening the duration of pain after an inflammatory insult.
The research team ran a series of targeted experiments to confirm the mechanism was not coincidental. When they blocked IL-10 signaling, ablated the IL-10 receptor (IL-10R1) on sensory neurons, or depleted monocytes entirely, pain resolution in males slowed dramatically, according to full‑text data hosted at PubMed Central. Each intervention independently disrupted recovery, confirming that the monocyte (IL-10) neuron pathway is not just correlated with faster healing but functionally required for it. Females, whose monocytes were less active in producing IL-10, did not show the same sharp recovery curve in the first place, underscoring that the pathway is inherently sex-biased rather than simply underused.
Hormones and the Immune, Nerve Conversation
Why do male monocytes produce more IL-10? Evidence points to sex hormones, particularly testosterone, as key regulators of this immune, nerve conversation. A study co-author from Michigan State University, writing in an expert commentary, explained that testosterone influences IL-10 output from monocytes, giving males a built-in advantage in shutting down inflammatory pain after injury. When testosterone levels are higher, monocytes appear more likely to adopt an anti-inflammatory profile, which in turn sends stronger “all clear” signals to pain-sensing neurons once tissue damage begins to resolve.
The female side of the hormonal equation is not simply a deficit story. Separate research from UC San Francisco found that estrogen and progesterone act on regulatory T cells, known as Tregs, in the meninges near the spinal cord of female mice. Those hormones increase production of enkephalin, an endogenous opioid, producing sex-specific behavioral effects on pain. Females therefore engage their own hormone-sensitive immune circuits to modulate discomfort, but through a different cellular pathway than the monocyte-driven IL-10 system that appears to give males faster resolution of acute inflammatory episodes. The practical consequence is that a single pain treatment strategy is unlikely to work equally well for both sexes, because the underlying biology is tuned by different hormones and cell types.
Broader Sex Differences in Pain Biology
The IL-10 finding fits into a broader pattern of sex-differentiated pain biology that researchers have been mapping for years. A review in Neuroscience and Biobehavioral Reviews cataloged mechanisms that differ between males and females, including microglia-related pathways in the spinal cord, calcitonin gene-related peptide (CGRP) signaling, and prolactin’s effects on sensory neurons. These systems influence how pain is initiated, amplified, and quieted over time. The monocyte (IL-10) pathway adds another layer to this picture, notable for its directness: a single immune cell type communicating with a specific class of neurons to produce a measurable difference in how long inflammatory pain lasts.
A separate line of evidence from the National Institutes of Health reinforces the idea that male and female bodies suppress pain through fundamentally different mechanisms. In a controlled human study summarized by NIH, researchers found that the opioid-blocking drug naloxone eliminated meditation-related pain relief in males but not in females. That result implies men rely more heavily on endogenous opioid pathways to reduce pain, while women engage non-opioid systems. When combined with the IL-10 monocyte data, the emerging picture is one of parallel but distinct pain-resolution architectures, not a simple case of one sex being “better” at handling pain than the other. Each sex appears to lean on its own mix of immune, hormonal, and neural pathways to bring pain back under control.
From Mouse Models to Human Health
The clinical stakes are significant. According to Michigan State University, about 50 million Americans suffer from chronic pain, and women are disproportionately affected. Current pain management protocols, from NSAIDs and corticosteroid injections to opioids and physical therapy, are largely sex-neutral, treating pain as a single biological phenomenon with a single set of solutions. The monocyte research challenges that assumption at the cellular level. If IL-10 production is a rate-limiting step in how quickly inflammation-driven pain resolves, then boosting IL-10 signaling in patients whose monocytes are less active could, in theory, accelerate recovery without the addiction risks associated with long-term opioid prescriptions.
Translating that idea into therapies will take time. Findings in mice do not always map cleanly onto humans, and IL-10 is a powerful immune regulator that can affect infection risk, wound healing, and even cancer surveillance. As highlighted in a news release from India’s public broadcaster, the MSU team’s work has already drawn international attention for showing that male immune systems mount a stronger IL-10 response that speeds pain resolution. Any attempt to mimic that response pharmacologically in women (or in men whose monocytes are less responsive) will have to be carefully calibrated so that dialing down inflammation does not inadvertently weaken other aspects of immune defense.
Rethinking Pain Research and Patient Care
The new findings also underscore a broader shift in how scientists design pain studies. For decades, many preclinical experiments relied heavily on male animals, in part to avoid hormonal cycling as a confounding factor. The IL-10 work illustrates why that approach is no longer acceptable: studying only males can hide mechanisms that matter more in females, and vice versa. Modern databases such as the National Center for Biotechnology Information now make it easier for researchers to compare datasets across sexes, while funding agencies increasingly expect sex to be treated as a biological variable rather than a nuisance to be averaged away.
For patients and clinicians, the message is not that existing treatments are useless, but that they may be incomplete. Resources like MedlinePlus already emphasize that chronic pain conditions—including arthritis, migraines, and neuropathies—often present differently in women than in men. The IL-10 monocyte pathway provides a concrete mechanistic explanation for at least one piece of that disparity, specifically in inflammatory pain that normally resolves over days to weeks. In the future, physicians may be able to pair standard therapies with immune-targeted interventions tailored to an individual’s sex, hormone status, and immune profile, moving pain care closer to true precision medicine.
Education will be crucial in making that shift. Programs supported by the NIH Office of Science Education, such as the Science Education partnership, are already working to bring concepts like sex differences in biology into classrooms and outreach efforts. As students and trainees learn that male and female bodies can use different cellular pathways to solve the same physiological problem, they are better prepared to question one-size-fits-all assumptions in medicine. That cultural change in the lab and clinic could be as important as any single discovery in shaping how the next generation of researchers approaches chronic pain.
Ultimately, the discovery of IL-10–producing monocytes as a key driver of faster pain recovery in male mice does not diminish women’s resilience or invalidate their pain experiences. Instead, it helps explain why women are more likely to become trapped in long-lasting inflammatory pain after similar injuries. By combining mechanistic insights from animal studies with careful human research and robust clinical data, scientists hope to turn these sex-specific differences into targeted solutions—so that fewer people, regardless of sex, find themselves living with pain that refuses to let go.
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*This article was researched with the help of AI, with human editors creating the final content.
