Summary: Decades of clinical observation show that women experience chronic pain more often and for longer periods than men. New research identifies a biological mechanism behind this disparity: hormone-regulated immune cells called monocytes that produce interleukin-10 (IL-10), a molecule that actively signals neurons to stop sending pain signals.
The study found that higher male levels of sex hormones, such as testosterone, prime monocytes to produce IL-10 more effectively. In males this leads to faster shutdown of pain signals and quicker recovery. In females, monocytes produce less IL-10, which contributes to slower pain resolution and greater risk of persistent pain. The discovery reframes chronic pain from a problem of how it begins to a problem of why it persists, pointing toward new non-opioid strategies that promote active resolution of pain.
Key Facts
- Active pain resolution: Recovery from pain is driven by immune activity—specifically monocyte-derived IL-10—rather than being a passive fade-out.
- The testosterone connection: Androgen signaling increases monocyte production of IL-10, effectively serving as an “off switch” for pain in males.
- Slower recovery in females: Lower activity of IL-10–producing monocytes in females correlates with delayed resolution and longer pain duration.
- Direct neural-immune communication: IL-10–producing monocytes act on IL-10 receptor–expressing sensory neurons to reduce neuronal excitability and stop pain signaling.
- Therapeutic potential: Targeting this immune–neural pathway could yield non-opioid treatments that accelerate pain resolution rather than simply blocking pain signals.
Source: Michigan State University
Chronic pain lasts longer for women than men; differences in hormone-regulated immune cells called monocytes may explain why.
A team at Michigan State University reports in Science Immunology that a subset of monocytes produces IL-10, a cytokine that signals sensory neurons to stop firing pain signals. The researchers observed that male animals and human patients had more active IL-10–producing monocytes, a pattern linked to higher androgen levels such as testosterone.
In contrast, females showed fewer IL-10–producing monocytes and experienced slower recovery from inflammatory pain. Geoffroy Laumet, MSU associate professor of physiology, with former graduate student Jaewon Sim, confirmed the pattern across mouse models and human clinical data.
Funded by the National Institutes of Health and the Department of Defense, the study suggests these immune cells could be stimulated to produce more IL-10 and help the body actively resolve pain. While clinical treatments based on this finding are likely years away, the research opens the door to non-opioid approaches aimed at preventing chronic pain and improving care—especially for women.
“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.”
Acute pain begins when sensory neurons are activated by injury or stimulation. In most people, that activity subsides as healing progresses. In chronic pain, however, neurons can remain hyperactive and maintain pain even after the original trigger is gone. Standard clinical evaluation—such as asking patients to rate pain on a scale—captures subjective experience but does not reveal underlying biological differences that shape recovery.
Laumet’s lab noticed unexpectedly higher levels of IL-10 in male samples during an early pilot study. Following up with more extensive experiments, including high-dimensional spectral flow cytometry, they identified IL-10–producing monocytes as key players in signaling sensory neurons to stop signaling pain. When male sex hormones were blocked experimentally, the abundance and activity of these IL-10–producing monocytes declined, confirming a hormonal influence.
The researchers validated their findings across multiple mouse experiments—for which they ran at least five distinct tests—and then collaborated with Sarah Linnsteadt at the University of North Carolina, who observed a similar sex-dependent pattern in people recovering from traumatic injuries: men had higher circulating IL-10 and monocyte counts and resolved pain more quickly.
This evidence reframes the problem of chronic pain by highlighting an immune-driven resolution pathway. The immediate research goal is to identify interventions that directly enhance IL-10 production or mimic its effects on sensory neurons, which could allow pain to resolve faster without relying on opioids.
“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.”
Key Questions Answered:
A: The study demonstrates a biological difference: immune cells in females produce less IL-10, slowing the process that naturally turns off pain. This supports a physiological basis rather than only differences in reporting or perception.
A: Although androgens stimulate IL-10 production, the researchers do not advocate using hormone therapy as the primary solution. Instead, the goal is to find ways to activate monocytes or replicate IL-10’s effects directly, independent of hormone levels.
A: Most current pain treatments block pain signaling temporarily. This research aims to speed the body’s own resolution of pain, offering a potential route to non-opioid therapies that reduce reliance on drugs that merely mask symptoms.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by the editorial team.
- Additional context was added by staff to clarify clinical and research implications.
About this pain and neuroscience research news
Author: Bethany Mauger
Source: Michigan State University
Contact: Bethany Mauger – Michigan State University
Image: The image is credited to Neuroscience News
Original Research: Open access. “Monocyte-derived IL-10 drives sex differences in pain duration” by Jaewon Sim et al., published in Science Immunology. DOI: 10.1126/sciimmunol.adx0292.
Abstract
Monocyte-derived IL-10 drives sex differences in pain duration
Women frequently experience longer-lasting pain than men, indicating delayed pain resolution, but the mechanisms underlying this sex difference remain unclear. This study shows that IL-10–producing monocytes resolve inflammatory pain by signaling to IL-10R1–expressing sensory neurons in a mouse model of skin inflammation. Male mice exhibited faster pain resolution than females, corresponding to higher numbers of IL-10–producing monocytes. In both sexes, deleting Il10 from monocytes or Il10ra from sensory neurons impaired pain resolution. Androgen signaling promoted IL-10 production by monocytes and contributed to the sex differences observed. Enhancing IL-10–producing monocytes with resolvin D1 accelerated pain resolution in both sexes. Human data following traumatic injury demonstrated faster pain resolution in men and higher circulating monocyte and IL-10 levels, consistent with the animal findings. These results identify peripheral IL-10–producing monocytes as key mediators of sex-specific pain resolution and highlight immune mechanisms that could be targeted to prevent chronic pain.