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Estrogen-Induced Monocytic Response Correlates with TMD Pain: A Case Control Study
M C Ribeiro-Dasilva1,2, R B Fillingim2, S M Wallet3
11 Department of Restorative Dental Science, University of Florida, Gainesville, FL, USA.
Journal of Dental Research
|November 19, 2016
Summary
Women with temporomandibular disorders (TMD) show an exaggerated inflammatory response in monocytes, which is amplified by estrogen. This heightened inflammation correlates with increased pain sensitivity in these individuals.
Area of Science:
- Immunology
- Endocrinology
- Pain Research
Background:
- Temporomandibular disorders (TMD) cause significant pain and dysfunction, affecting 4-10% of the population, with higher prevalence in women during reproductive years.
- The role of sex hormones, particularly estrogen, is implicated in TMD pathophysiology due to increased prevalence in females and lower rates in childhood.
- Understanding the inflammatory mechanisms in TMD is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate if women with TMD exhibit a monocytic hyperinflammatory response compared to controls.
- To examine the association between monocytic inflammatory responses and clinical pain levels in women with TMD.
- To determine the influence of estrogen on the inflammatory response of monocytes from women with TMD.
Main Methods:
- Eighteen women (aged 18-35) with TMD were studied during their follicular menstrual phase.
- Monocytes were isolated and stimulated with lipopolysaccharide (LPS), a toll-like receptor (TLR)-4 ligand, with and without estrogen.
- Interleukin-6 (IL-6) expression levels were measured to assess inflammatory response, alongside clinical pain questionnaires and RDC exams.
Main Results:
- Women with TMD demonstrated a systemic hyperinflammatory phenotype, releasing increased cytokines from monocytes after inflammatory stimulation.
- Estrogen further amplified this monocytic inflammatory response in women with TMD.
- Higher self-reported pain on the Visual Analog Scale (VAS) correlated with increased IL-6 production by monocytes.
Conclusions:
- Women with TMD exhibit an estrogen-enhanced hyperinflammatory monocyte response.
- This estrogen-induced hyperinflammation may contribute to heightened clinical pain in TMD, potentially through central sensitization.
- Further research is warranted to explore the therapeutic implications of targeting inflammatory pathways in TMD.

