Identification of novel mechanisms involved in generating localized vulvodynia pain
Open accessAbstract
Objective Our goal was to gain a better understanding of the inflammatory pathways affected during localized vulvodynia, a poorly understood, common, and debilitating condition characterized by chronic pain of the vulvar vestibule.Study design In a control matched study, primary human fibroblast strains were generated from biopsies collected from localized provoked vulvodynia (LPV) cases and from age- and race-matched controls. We then examined intracellular mechanisms by which these fibroblasts recognize pathogenic Candida albicans; >70% of vulvodynia patients report the occurrence of prior chronic Candida infections, which is accompanied by localized inflammation and elevated production of proinflammatory/pain-associated interleukin (IL)-6 and prostaglandin E2 (PGE2). We focused on examining the signaling pathways involved in recognition of yeast components that are present and abundant during chronic infection.Results Dectin-1, a surface receptor that binds C albicans cell wall glucan, was significantly elevated in vestibular vs external vulvar cells (from areas without pain) in both cases and controls, while its abundance was highest in LPV cases. Blocking Dectin-1 signaling significantly reduced pain-associated IL-6 and PGE2 production during the response to C albicans. Furthermore, LPV patient vestibular cells produced inflammatory mediators in response to low numbers of C albicans cells, while external vulvar fibroblasts were nonresponsive. Inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (proinflammatory transcription factor) nearly abrogated IL-6 and PGE2 production induced by C albicans, in keeping with observations that Dectin-1 signals through the nuclear factor kappa-light-chain-enhancer of activated B cells pathway.Conclusion These findings implicate that a fibroblast-mediated proinflammatory response to C albicans contributes to the induction of pain in LPV cases. Targeting this response may be an ideal strategy for the development of new vulvodynia therapies.
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Confirmation of the presence of Candida by PCR can be valuable in the management of RVVC patients who can show hypersensitivity to even the lowest concentrations of Candida antigens.
“Although detection of Candida in asymptomatic patients is not necessarily a significant finding requiring medication, the confirmation of the presence of Candida by PCR techniques can be extremely valuable in the management of patients with RVVC who can show a hypersensitivity to even the lowest concentrations of Candida antigens (Bernstein and Seidu, 2015; Falsetta et al., 2015).”
From Management of recurrent vulvovaginal candidosis: Narrative review of the literature and European expert panel opinion (2022) · cites this paper as Falsetta et al., 2015
Detection of Candida in asymptomatic patients is not necessarily a significant finding requiring medication.
“Although detection of Candida in asymptomatic patients is not necessarily a significant finding requiring medication, the confirmation of the presence of Candida by PCR techniques can be extremely valuable in the management of patients with RVVC who can show a hypersensitivity to even the lowest concentrations of Candida antigens (Bernstein and Seidu, 2015; Falsetta et al., 2015).”
From Management of recurrent vulvovaginal candidosis: Narrative review of the literature and European expert panel opinion (2022) · cites this paper as Falsetta et al., 2015
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- Authors
- Falsetta, M. L., Foster, D. C., Woeller, C. F., Pollock, S. J., Bonham, A. D., Haidaris, C. G., Stodgell, C. J., & Phipps, R. P.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Phipps, Richard P.
- ORCID
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 213
- Issue
- 1
- Pages
- 38.e1-38.e12
- ISSN
- 0002-9378 (ISSN-L)
- PMC
- PMC4485605
- OpenAlex
- W2045670441
- Cited by
- 69
- References
- 81
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 9 · 2015: 1
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Child Health and Human Development (R01 HD069313)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Surgery › Genital Health and Disease
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Keywords
- vulvodynia, provoked vulvodynia, Candida albicans, Dectin-1, fibroblasts, NF-κB signaling, interleukin-6, prostaglandin E2, chronic fungal infection, vulvar inflammation, pain mechanisms
- MeSH terms
- Dectin-1, Adult, Candidiasis, Vulvovaginal, Female, Fibroblasts, Humans, Inflammation, Pain, Dinoprostone, Interleukin-6, NF-kappa B, Lectins, C-Type, Vulvodynia, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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