Vulvar vestibulitis syndrome : pathophysiology of the vestibular mucosa

Objective: The main purpose of the study was to survey possible pathophysiological changes of the vestibular mucosa in women with vulvar vestibulitis syndrome with regard to the clinical findings of superficial dyspareunia and mucosal erythema.

Methods: Biopsies analysed with immunohistochemistry were used to study the morphology, distribution and neuropeptide content of the peripheral nerves, and the microvascularisation of the vestibular mucosa. The somatosensory function of the vestibular nerves was analysed with quantitative sensory testing (QST). Immunohistochemistry and Western dot-blot analyses were used to study the expression of the inflammatory markers COX 2 and NOS in vestibular tissue specimens. The superficial blood flow in the vestibular mucosa was registered with laser Doppler perfusion imaging (LDPI) and correlated to mucosal erythema. The constrictive ability of the vestibular arterioles was studied with LDPI before and after submucosal injection of noradrenaline.

Results: Increased number of intraepithelial free nerve endings were found in women with vestibulitis. These nerve fibres were immunopositive for calcitonin gene-related peptide, a neoropeptide with vasodilative capacity. QST revealed lower thresholds for thermal perception and painful stimulation by von Frey filaments, and heat and distension of the vaginal introitus, in patients than in control subjects. Cold-evoked pain was more common among the patients whereas vibration was not painful in either patients or controls. The expression of the inflammatory markers COX 2 and iNOS was not elevated in the vestibular mucosa in women with VVS. A significant increase in superficial blood flow was registered in the erythematous posterior parts of the vestibular mucosa in the patients. However, there was no significant correlation between perfusion values and degree of erythema in the same individual. Microvascular density and the ability of vestibular arterioles to constrict did not differ between patients and controls.

Conclusions: There are structural and functional abnormalities of the peripheral sensory nerves in the vestibular mucosa in women with VVS. The somatosensory abnormalities, with decreased pain thresholds for mechanical and thermal stimuli, give psychophysical evidence of peripheral sensitisation and/or increased number of nociceptors in the vestibular mucosa. There is no evidence of an active inflammation in the mucosa. The increased blood flow, most probably caused by neurogenic vasodilatation contributes to, but does not fully explain, the erythema. Atrophic changes in the surface epithelium should also be considered in the evaluation of an erythema.

List of scientific papers

I. Bohm-Starke N, Hilliges M, Falconer C, Rylander E (1998). "Increased intraepithelial innervation in women with vulvar vestibulitis syndrome. " Gynecol Obstet Invest 46(4): 256-60
https://pubmed.ncbi.nlm.nih.gov/9813445

II. Bohm-Starke N, Hilliges M, Falconer C, Rylander E (1999). "Neurochemical characterization of the vestibular nerves in women with vulvar vestibulitis syndrome. " Gynecol Obstet Invest 48(4): 270-5
https://pubmed.ncbi.nlm.nih.gov/10592432

III. Bohm-Starke N, Hilliges M, Brodda-Jansen G, Rylander E, Torebjork E (2001). "Psychophysical evidence of nociceptor sensitization in vulvar vestibulitis syndrome." Pain (In Print)

IV. Bohm-Starke N, Falconer C, Rylander E, Hilliges M (2001). "The expression of cyclooxygenase 2 and inducible nitric oxide synthase indicates no active inflammation in vulvar vestibulitis. " Acta Obstet Gynecol Scand 80(7): 638-44
https://pubmed.ncbi.nlm.nih.gov/11437722

V. Bohm-Starke N, Hilliges M, Blomgren B, Falconer C, Rylander E (2001). "Increased blood flow and erythema in the posterior mucosa vulvar vestibulitis." Obstetrics and Gynecology (In Print)