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 Have you noticed that women around you seem to be more sensitive to pain and plagued more by chronic pain? Clinically, the incidence of chronic pain in women is far higher than in men, and the reason behind this is not just a difference in "tolerance"—it’s the gender-specific role of immune cells in the body at play!
In February 2026, Science Immunology published a landmark study by a team from Michigan State University, which for the first time identified the key player mediating gender differences in pain: IL-10+ monocytes. This study provides a complete cellular and molecular explanation for why pain relief is faster in men and why women are more likely to suffer from chronic pain. 

01.Core Answer: A Single Immune Cell Determines the Gender Gap in the Speed of Pain Relief
Chronic pain is a globally prevalent health issue, affecting over 100 million people in the United States alone, with women facing a risk several times that of men. Previously, it was widely believed that this might be related to hormones and neural sensitivity, but a clear core mechanism remained elusive.
Using inflammatory skin pain as a model, this study found that pain in male mice began to subside after one week, while pain in female mice persisted for much longer—and there was no difference in the degree of inflammation between the two genders. The core of the problem lies in IL-10+ monocytes at the inflamed site.
Scientists detected via ELISA that the levels of IL-10 protein at the inflamed site in male mice were significantly higher than in females, and the number of corresponding IL-10+ monocytes was more than twice that in females. These cells are the body’s "pain relief specialists", and IL-10 is the key pain-relieving molecule they secrete—this finding was also validated in human clinical data. Researchers found that specifically reducing these immune cells led to a sharp drop in IL-10 levels and a significant delay in pain relief in both genders, proving that these cells are the core executors of pain relief.

(A, B) UMAP plots of skin immune cells after CFA treatment and heatmaps of the relative expression of surface markers, with cluster colors corresponding to cell types. (C) Quantification of skin immune cells after CFA treatment. (D, E) Plac8 and Ccr2 mRNA levels in the skin of WT mice 7 days after CFA treatment. (F) Light green in the UMAP plot indicates Il10-GFP+ cells in the skin immune cell population. (G) Number of Il10-GFP+ cells in male and female mice. (H) Correlation between the number of skin Il10-GFP+Ly6Chigh myeloid cells and mechanical pain threshold 6 days after CFA treatment, R²=0.55, Pearson r=0.7444 (females: red triangles; males: blue squares). (I) Gating strategy for the selective identification of monocytes/macrophages. (J) UMAP plot showing 3 monocyte subsets, 2 MdM subsets, and 1 TRM subset. (K) Heatmap of relative surface marker expression; monocyte subsets highly express Ly6C and CCR2. (L) Distribution of each subset in the inflamed skin of male and female mice. (M) Left panel: light green in the UMAP plot indicates the distribution of Il10-GFP+ monocytes/macrophages; right panel: their proportion among monocytes/macrophages. (N) Quantification of Il10-GFP+ monocytes/macrophages.

02.Mechanism of Action: Direct "Crosstalk" Between Immune Cells and Nerves for Precise Pain Relief
Many people assume that immune cells only regulate inflammation and indirectly relieve pain, but this study overturns that notion: IL-10+ monocytes directly "communicate" with sensory nerves to precisely inhibit pain perception. The IL-10 molecules secreted by these immune cells bind to IL-10R1—the "receptor" on the surface of peripheral sensory neurons—and this binding directly reduces neuronal excitability, preventing pain signals from being transmitted smoothly and achieving rapid pain relief. Experiments also showed no gender difference in the number of these "receptors" on neurons, meaning the gender gap in pain is purely due to differences in the amount of pain-relieving molecules secreted by immune cells.
In experiments, injecting synthetic IL-10 at the inflamed site increased local IL-10 concentrations and accelerated pain relief in both male and female mice; conversely, blocking the action of this molecule prolonged pain, further confirming its core pain-relieving role.

03.Underlying Regulation: Androgens Are the "Activators" of Pain-Relieving Cells
Why do men have more IL-10+ monocytes? The study identified the key upstream regulator: androgens. When female mice were supplemented with androgens, researchers found a significant increase in their IL-10 protein levels and a substantial rise in the number of these pain-relieving immune cells, with their pain relief speed matching that of male mice. Conversely, inhibiting androgen activity in male mice led to a marked decrease in IL-10 expression, a reduction in immune cells, and slower pain relief. Simply put, androgens directly "activate" monocytes to secrete pain-relieving molecules more efficiently—this is a key reason why pain relief is faster in men.

(A) Flow cytometry gating strategy for identifying monocytes from other CD45+ cells in the skin after CFA treatment; the MHCII/CD11c flow plot is consistent with Figure 2I. (B, C) Representative UMAP plots of skin monocyte subsets after CFA treatment, generated by randomly sampling 20,000 monocytes from 8 mice; monocytes were divided into four clusters—"inflammatory", MHCII+, CD206high, and CD44high—based on marker expression. (D) Distribution of each cluster in Il10-GFP+ and Il10-GFP- monocytes. (E) Frequency of Il10-GFP+ monocytes in each cluster. (F) Quantitative statistics of Il10-GFP+ monocytes in each cluster by gender.

04.A Surprising Finding: One Molecule Can Eliminate the Gender Gap in Pain
 The study also yielded a highly applicable discovery: Resolvin D1 (RvD1), a pro-resolution lipid mediator, can target and increase the number of IL-10+ monocytes in both male and female mice, with a marked rise in IL-10 levels observed in both genders. This effectively eliminates the difference in pain relief speed between them and significantly accelerates pain relief in females. This finding offers a completely new approach for the treatment of chronic pain: in the future, it may be possible to develop novel pain relief interventions by targeting and regulating these immune cells, helping more chronic pain patients—especially women—break free from their suffering. However, the study shows that not all monocytes can relieve pain; the CD206high subset is the main "producer" of pain-relieving molecules, which also locks in a more specific target for subsequent precise research and intervention.
This study also reveals that many gender differences in bodily sensations are not a matter of "subjective feeling" but are determined by objective cellular and molecular differences. These hidden differences are being uncovered one by one through advancing biological detection technologies, giving us a more scientific and detailed understanding of our own bodily mechanisms.

Original link: https://www.science.org/doi/10.1126/sciimmunol.adx0292