Chronic pain in women: exploring the immune pathway

By Elodie Vaz  | Published on February 24, 2026 | 3 min read

Chronic pain represents a major public health challenge. Defined by its persistence beyond three to six months, it differs from acute pain by its pathophysiological autonomy: sensory neurons remain activated despite resolution of the initial injury, or even in the absence of peripheral stimulation.

Although differences in prevalence and persistence between sexes are well documented, their biological determinants remain insufficiently elucidated. Clinically, assessment still relies largely on self-reported scales (1 to 10), which are subject to significant interindividual variability. The higher frequency of pain complaints among women has therefore often been interpreted through the lens of reporting bias or psychological factors.  

Research published on February 20 in Science Immunology by the team of Professor Geoffroy Laumet (Michigan State University) proposes a paradigm shift by identifying a sexually dimorphic immuno-neuronal mechanism involved in pain resolution.  

The study aimed to determine whether immune differences regulated by sex hormones could contribute to the greater persistence of chronic pain in women.

 “The difference in pain perception between men and women has a biological basis,” stated Professor Geoffroy Laumet in a press release. “It is not psychological, and you are not fragile. It is related to your immune system.”  

Suspicion falls on monocytes

More specifically, the researchers investigated the role of a subset of monocytes producing interleukin-10 (IL-10), an anti-inflammatory cytokine known to inhibit nociceptive neuron activity.  

The work relied on a translational approach combining murine models and human cohorts. In a pilot phase, the team observed higher plasma levels of IL-10 in males. “That was a turning point for me,” said Professor Jaewon Sim, a former doctoral researcher in the laboratory and co-author of the study. The researchers then used high-dimensional spectral flow cytometry to precisely characterize monocyte subpopulations. Five distinct experimental paradigms in mice confirmed the robustness of the observed phenomenon.  

Analyses showed that a subgroup of monocytes migrates to injured tissues and releases “a molecule that silences pain-sensitive neurons,” according to Geoffroy Laumet. Hormonal influence was tested by modulating male sex hormones: blocking testosterone reversed the monocyte activation profile and reduced IL-10 production.  

In parallel, a collaboration with Professor Sarah Linnstaedt at the University of North Carolina at Chapel Hill enabled evaluation of patients involved in motor vehicle accidents. Circulating levels of IL-10–producing monocytes and IL-10 itself were correlated with trajectories of pain resolution.  

The results converged across murine and human models. Males exhibited higher numbers of active IL-10–producing monocytes, associated with faster pain decline after trauma. In contrast, females showed reduced monocyte activity accompanied by prolonged persistence of pain symptoms.  

Testosterone as a modulator  

Testosterone appears to be a key factor, “promoting the production by these white blood cells of the molecule that calms neurons,” Professor Laumet explained. “This study shows that pain resolution is not a passive process,” he added. “It is an active process driven by the immune system.”  

These findings shift the focus of research: beyond mechanisms of nociceptive initiation, the dynamics of immuno-neuronal resolution emerge as a central determinant of chronicity. For Elora Midavaine of the University of California, this discovery fills “an important gap”: although sex differences in pain are well documented, the underlying mechanisms have remained “poorly understood.”

 Identification of a monocyte–IL-10–sensory neuron axis modulated by sex hormones provides a biological foundation for sex differences in pain persistence. “There are real biological reasons why women experience prolonged pain,” insists Geoffroy Laumet.  

Rethinking pain medicine  

These results open the way to therapeutic strategies aimed not solely at blocking nociceptive signals but at activating endogenous resolution pathways. “Future researchers will be able to build on this work,” he concluded. “It opens new perspectives for non-opioid therapies aimed at preventing chronic pain before it becomes established.”  

In the longer term, this approach may help reshape pain medicine through the lens of immune and hormonal dimorphism, and encourage more systematic integration of sex as a biological variable in clinical trial design and analgesic strategies.  


                      Read next: Should nerve blocks become the norm in children?




About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.