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Monocyte-derived IL-10 drives sex differences in pain duration
Jaewon Sim1,2, Elizabeth O'Guin1, Chiho Sugimoto1
1Department of Physiology, Michigan State University, East Lansing, MI, USA.
Science Immunology
|February 20, 2026
Summary
Sex differences in pain resolution involve interleukin-10 (IL-10) producing monocytes. These monocytes signal to sensory neurons, with androgens influencing IL-10 levels, impacting pain duration in both mice and humans.
Area of Science:
- Immunology
- Neuroscience
- Pain Research
Background:
- Women often experience longer-lasting pain than men, suggesting delayed pain resolution.
- The precise biological mechanisms driving these sex-based differences in pain resolution are not fully understood.
Purpose of the Study:
- To investigate the role of interleukin-10 (IL-10) producing monocytes in sex-specific inflammatory pain resolution.
- To elucidate the signaling pathways and molecular mechanisms underlying these sex differences in pain.
Main Methods:
- Utilized a mouse model of skin inflammation to study pain resolution.
- Employed genetic manipulation (gene deletion) in monocytes and sensory neurons to assess the impact of IL-10 signaling.
- Investigated the influence of androgen signaling on monocyte IL-10 production.
- Analyzed human data from traumatic injury patients to correlate pain resolution with monocyte and IL-10 levels.
Main Results:
- Interleukin-10 positive (IL-10+) monocytes were found to resolve inflammatory pain by signaling to IL-10 receptor 1 positive (IL-10R1+) sensory neurons.
- Male mice showed faster pain resolution than females, linked to higher IL-10+ monocyte numbers.
- Impaired pain resolution was observed when IL-10 was deleted from monocytes or IL-10RA from sensory neurons in both sexes.
- Androgen signaling enhanced IL-10 production by monocytes, contributing to sex differences in IL-10+ monocyte abundance.
- Administration of resolvin D1 to boost IL-10+ monocytes accelerated pain resolution in both male and female mice.
- Human data indicated faster pain resolution in men post-injury, associated with higher circulating monocytes and IL-10 levels.
Conclusions:
- Peripheral IL-10+ monocytes play a critical role in sex-specific resolution of inflammatory pain.
- Androgen signaling significantly influences IL-10+ monocyte levels, contributing to observed sex differences.
- These findings highlight immune system mechanisms involved in pain resolution and offer potential targets for preventing chronic pain.
