Localized provoked vulvodynia (LPV) is a subset of vulvodynia, associated with induced pain by touch on vulvar mucosa in the absence of any other recognizable disease. The intensity of pain is out of proportion to the applied pressure: very light touch evokes excessively strong pain, a phenomenon defined as allodynia.Different vulvovaginal infections, especially recurrent candidiasis, and urinary tract infections are known risk factors for LPV. LPV patients, more often than healthy controls, are genetically predisposed to yeast and other vulvo-vaginal infections. Animal models and in vitro studies have further produced data of the significance of Candida albicans infection as a pain generator in the vulvar vestibule. Studies conducted in cell cultures have shown that fibroblasts originating from vestibular mucosa of LPV patients are more responsive to fungal antigens than those from healthy controls. LPV patients also have a tendency to carry pro-inflammatory allele variants of IL-1beta and IL-1 receptor antagonist genes and show elevated tissue levels of pro-inflammatory cytokines.An increased immunoinflammatory response and the neuroinflammatory axis may well be involved in the development of a chronic pain syndrome.
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Recently we demonstrated the existence of secondary lymphoid tissue, the vestibule associated lymphoid tissue (VALT) in vestibular mucosa and showed that this VALT had become activated in LPV. In VALT, like in other mucosa-associated lymphoid tissues (MALT), antigen presenting dendritic cells transport foreign antigens to germinal centers where the initiation of an immune response (B and T cell activation) takes place. We also found more intra epithelial nerve fibers (IENF) in the patients than in the controls (small unmyelinated C-fibers and thinly myelinated A-delta fibers). The IENFs tended to center around such areas of the mucosa and vestibular glands, which showed increased B lymphocyte infiltration. Also, the density and presence of IENFs were higher in samples with more pronounced immune activation.
This further supports the essential role of immune activation in the altered pain sensation of LPV. Interplay between activated immune cells and biomodulators of the signaling of sensory neurons could thus be involved in LPV.
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