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
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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.
