Researchers report a biological reason why women often experience longer-lasting pain than men after similar injuries. A study published Friday in Science Immunology followed 245 people after traumatic events — mostly car accidents — and found that men’s pain tended to resolve faster over a roughly three-month period. Blood tests and laboratory experiments pointed to higher levels of the anti-inflammatory molecule interleukin-10 (IL-10) in males, a response that the team links to testosterone-driven activity in certain white blood cells. The authors and external experts say the results help explain sex differences in post-traumatic pain and could point to new treatment directions for persistent pain in women.
Key Takeaways
- Sample and follow-up: The human cohort included 245 trauma patients, primarily from car crashes, tracked for nearly three months after injury.
- Initial pain parity: Men and women reported similar pain severity on the day of injury, but men’s pain declined faster during follow-up.
- Immune signal: Men showed higher circulating levels of interleukin-10 (IL-10), a molecule that helps switch off pain signals.
- Hormonal link: Researchers found that testosterone increased IL-10 production from white blood cells in their experiments.
- Mice mirror humans: Male mice recovered more quickly than females after inflammatory stimuli, surgical incision, and two-hour restraint stress.
- Scope limits: The findings address post-traumatic and post-surgical persistent pain; non-trauma conditions like fibromyalgia may not follow the same pathway.
- Treatment implications: Authors suggest immune- or hormone-targeted topical approaches could be explored to help women with chronic post-injury pain.
Background
Clinicians and researchers have long observed that women report chronic pain at higher rates than men and that pain often lasts longer after the same injury. Historically, some practitioners attributed these differences to reporting behavior or psychosocial factors, but accumulating evidence points to biological contributors. Sex differences in immune function and hormone signaling have emerged as plausible mechanisms; prior studies have shown that men and women can mount qualitatively different innate immune responses to stress and injury.
Persistent pain after trauma or surgery is a major public-health problem because it reduces quality of life and resists many standard therapies. Many commonly used pain treatments—nonsteroidal anti-inflammatory drugs, opioids, antidepressants or anticonvulsants—have limited long-term benefit or carry risks such as addiction, gastrointestinal harm, or organ damage. That landscape has heightened interest in identifying sex-specific biological pathways that could be targeted safely and effectively.
Main Event
The new study enrolled 245 people who had experienced traumatic injuries, mostly from motor vehicle crashes, and asked them to rate their pain over a follow-up period that approached three months. Although initial pain intensity was similar between sexes on the day of injury, men’s pain scores declined faster during the weeks that followed. Blood assays taken during recovery showed that men had higher circulating levels of IL-10, an anti-inflammatory cytokine known to modulate pain signaling to the brain.
To probe mechanism, the research team tested immune responses in laboratory mice. They administered compounds that trigger inflammation, made a small surgical incision, and subjected mice to two hours of restraint to mimic combined physical and emotional stress. In these models, male mice showed signs of resolution of pain behaviors more quickly than female mice, and investigators found greater activity in IL-10–producing white blood cells in males.
At the cellular level, the study reports that testosterone enhanced IL-10 production from certain leukocytes in vitro and in animal experiments, suggesting a hormone-driven boost to a pathway that helps terminate pain. The lead author described these effects as coming from immune cells rather than from psychological differences, framing the finding as a bona fide biological mechanism for sex-specific pain resolution.
Analysis & Implications
The study strengthens a growing view that innate immune signaling, modulated by sex hormones, contributes to how quickly pain resolves after an injury. If testosterone promotes IL-10 production and thereby accelerates shutdown of pain signals, that could partially explain population-level differences in post-traumatic pain outcomes between men and women. The result fits with prior work showing sex-dependent immune strategies: males sometimes rely more on certain innate pathways while females may mount different inflammatory or adaptive responses.
Clinically, the finding suggests new therapeutic angles: enhancing IL-10 signaling at the injured site or locally delivering hormone-mediated modulators may help reduce the transition from acute to persistent pain in women. The authors cite topical or localized approaches as potentially preferable to systemic hormone therapy because they could carry fewer systemic side effects. However, translating a mechanistic link into a safe, effective treatment will require careful dose-finding, safety testing, and trials that account for age, comorbidities, and hormonal status.
There are important caveats. The study focuses on traumatic and post-surgical pain, not syndromes that lack a clear initiating injury, such as fibromyalgia or chronic widespread pain, which have complex, multifactorial causes. Moreover, sex differences are not absolute: many men develop long-term pain and many women recover quickly. The research points to tendencies at the group level, not deterministic outcomes for individuals.
Comparison & Data
| Measure | Males | Females |
|---|---|---|
| Human sample | 245 participants (mixed sexes) | 245 participants (mixed sexes) |
| Initial pain severity | Similar to females | Similar to males |
| Follow-up trend (~3 months) | Faster decline in pain | Slower decline in pain |
| IL-10 (blood) | Higher levels observed | Lower levels observed |
| Mice models | Faster behavioral recovery | Slower behavioral recovery |
The table summarizes the study’s principal comparisons without implying precise numerical IL-10 concentrations, which the paper reports in laboratory units; readers should consult the original publication for detailed assay values. The human cohort and animal models provide convergent evidence but differ in control over variables and the ability to isolate mechanisms, so the findings are complementary rather than redundant.
Reactions & Quotes
Investigators and outside experts framed the results as an important step toward recognizing biological contributors to sex differences in pain.
“What we show is, it’s a real biological mechanism from the immune cells. It’s not in the mind.”
Geoffroy Laumet, Associate Professor of Physiology, Michigan State University
Laumet emphasized immune-cell activity and its modulation by testosterone as central to the team’s interpretation. External scholars urged clinicians to take these differences seriously in practice.
“A lot of women are taught to hide their pain… these findings underscore the need to take women’s pain seriously.”
Ann Gregus, Assistant Professor, Virginia Tech (pain researcher)
Other experts cautioned against overgeneralizing the result beyond post-traumatic contexts.
“Does it explain everything? I don’t think so. We don’t have any single, magical pathway.”
Dr. Michele Curatolo, Professor of Anesthesiology and Pain Medicine, University of Washington
Unconfirmed
- Whether topical testosterone or other hormone-based patches will be both safe and effective for reducing chronic post-injury pain in women remains unproven and requires clinical trials.
- It is not confirmed that the IL-10 mechanism explains sex differences in non-traumatic chronic pain syndromes such as fibromyalgia.
- The study’s human cohort was concentrated on trauma patients, and broader population representativeness (age ranges, medical comorbidities, hormonal status) needs further validation.
Bottom Line
This research provides credible biological evidence that sex-linked immune responses — particularly IL-10 production influenced by testosterone — help explain why pain after similar injuries often resolves faster in men than in women. The work bridges human observational data and animal experiments to make a coherent mechanistic case, while stopping short of claiming the pathway explains all chronic pain conditions.
For clinicians and patients, the immediate takeaway is twofold: first, to treat reports of women’s post-injury pain with clinical seriousness; and second, to consider that future, targeted therapies might emerge from immune- and hormone-focused strategies. Key next steps are carefully designed clinical trials, safety assessments for any hormone-based interventions, and studies that explore whether similar mechanisms operate in non-traumatic pain disorders.
Sources
- NBC News — Coverage of the study (media report)
- Science Immunology — Journal (peer-reviewed publication)
- Michigan State University — Institutional affiliation of lead authors (academic)
- Virginia Tech — Institutional affiliation of an external expert (academic)
- University of Washington — Institutional affiliation of an external expert (academic)