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Localized provoked vulvodynia (LPV) presents with induced pain by touch on vulvar mucosa in the absence of any other recognizable disease (1). Vestibulodynia represents the pain sensation in the vulvar vestibular mucosa and results in severe dyspareunia. Pain intensity is out of proportion to the applied pressure: very light touch evokes excessively strong pain (allodynia).
Opinions on the etiopathogenesis of LPV differ, and the mechanisms resulting in the altered pain sensation are unknown. Recurrent vulvovaginal candidiasis has been considered as a risk factor for the disease (2). A tendency to an exaggerated inflammatory response and dysregulation of inflammation in affected women has been suggested (3). Also, there is evidence for a special genetic characteristic associated with an increased risk of recurrent vulvovaginal candidiasis in women with LPV (4). Since the immune and neuronal systems are closely interrelated an increased immunoinflammatory response may well predispose to the development of a chronic pain syndrome. The vulvar vestibule has also been suggested to possess a unique, embryologically defined immunoinflammatory responsiveness. In a recent study fibroblasts derived from a painful vestibular area were capable of producing a far more extensive inflammatory response than fibroblasts originating from other or non-painful areas of the vulvar mucosa (5).
Recently we demonstrated the existence of secondary lymphoid tissue, the vestibule-associated lymphoid tissue (VALT) in the vestibular mucosa and showed that VALT had become activated in LPV (6). In VALT, like in other mucosa-associated lymphoid tissues (MALT), the initiation of an immune response (B and T cell activation) takes place in germinal centers. In our material of 27 LPV patients and 15 healthy controls germinal centers were present in 14 patients as a sign of immune activation, and in none of the controls. 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 areas with increased B lymphocyte infiltration. Also, the density and presence of IENFs were higher in samples with more pronounced immune activation (Tommola P, et.al. unpublished). This further supports the pivotal role of immune activation in the altered pain sensation of LPV. An interplay between activated immune cells and biomodulators of the signaling of sensory neurons could thus be involved in LPV.
1. Moyal-Barracco M, Lynch PJ. 2003 ISSVD terminology and classification of vulvodynia: A historical perspective. J Reprod Med. 2004;49(10):772-777.
2. Farmer MA, Taylor AM, Bailey AL, et al. Repeated vulvovaginal fungal infections cause persistent pain in a mouse model of vulvodynia. Sci Transl Med. 2011;3(101):101ra91.
3. Foster DC, Sazenski TM, Stodgell CJ. Impact of genetic variation in interleukin-1 receptor antagonist and melanocortin-1 receptor genes on vulvar vestibulitis syndrome. J Reprod Med. 2004;49(7):503-509.
4. Lev-Sagie A, Prus D, Linhares IM, Lavy Y, Ledger WJ, Witkin SS. Polymorphism in a gene coding for the inflammasome component NALP3 and recurrent vulvovaginal candidiasis in women with vulvar vestibulitis syndrome. Am J Obstet Gynecol. 2009;200(3):303.e1-303.e6.
5. Foster DC, Falsetta ML, Woeller CF, et al. Site-specific mesenchymal control of inflammatory pain to yeast challenge in vulvodynia-afflicted and pain-free women. Pain. 2015;156(3):386-396.
6. Tommola P, Butzow R, Unkila-Kallio L, Paavonen J, Meri S. Activation of vestibule-associated lymphoid tissue in localized provoked vulvodynia. Am J Obstet Gynecol. 2015;212(4):476.e1-476.e8.