Urethral pain syndrome (UPS) is characterized by the occurrence of persistent or recurrent pain in the urethra in the absence of a confirmed infection and other obvious local pathological changes. The study of its pathogenetic aspects is important first of all for understanding the causes of the disease, to prescribe effective treatment, specific recommendations for the prevention and treatment of this disease are also absent. This paper presents the advanced experience of our research group on the study of the urethral state by the in vivo cross-polarization optical coherence tomography (CP OCT) method, and also the results of the microbiota analysis in the urethral tissues.
The purpose of the study is to search for the risk factors for UPS and the character of changes in the urethral tissues, using the data of: 1) concomitant pathology, 2) structural changes in the urethral wall in UPS in comparison with chronic cystitis of bacterial etiology 3) studying the microbiota of urethral tissues.
Materials and methods: The condition of the urethra was studied in 109 patients: 55 of them with UPS (group «UРS»), without clinical manifestations of inflammation; 41 – with chronic inflammation of the lower urinary tract of various origins (group «Inf»); in 14 patients with stones of the upper urinary tract without pyelonephritis, the urethra was taken as the norm (group «N»). All performed a clinical minimum of studies, also cystoscopy with the study of the bladder triangle, the neck of the bladder and the urethra by the method of in vivo tissue imaging – CP OCT. The device «OCT–1300U» with wavelength of 1300 nm is used. To determine the possible role of UPS disease background, the analysis of concomitant pathology preceding the development of UPS was performed. To analyze the relationship of changes in the urethral tissues with the composition of its microbiota, a PCR study of biopsies from the proximal segment of the urethra was performed in 13 patients with UPS.
Results: Qualitative comparison of the thickness and character of the OCT signal of the urethral wall layers observed using CP OCT in the studied groups of patients allowed us to establish that the state of the epithelium and connective tissue structures of the mucous membrane in patients with UPS is not the norm, changes are similar to those in chronic inflammation.
Changes in the character of the OCT signal were recorded in all parts of the urethra, but in the middle third they are most pronounced and most critical. In UPS, there is a brightly pronounced reorganization of the connective tissue stroma components. Pronounced fibrosis of subepithelial structures (increased signal brightness in the cross-channel compared to the norm) with their thickening was recorded in 48.2% of cases, and thinning/lack of visualization of the epithelial layer was detected in 20.5%, and in chronic inflammation 55.5% and 40.6% of cases, respectively. According to the results of PCR, only one patient had significant total bacterial contamination of the biopsy (TBС=104.7). In all other cases, the total bacterial mass of the biopsies was at the level of negative control.
Conclusions. In patients with UPS, the presence of several concomitant, often chronic, diseases was revealed, which may be a premorbid background and one of the risk factors for the occurrence and maintenance of UPS. Pilot PCR studies of biopsies from the proximal segment of the urethra indicate that low values of bacterial contamination in the majority of patients with UPS do not exclude the possible role of bacteria in the development of the disease in some patients.
The CP OCT method used in this study is currently the only one in vivo method of visualization of the urethral mucosa, which provides real-time images of structural changes in the epithelial (atrophy or hyperplasia) and connective tissue (active or latent inflammation with cellular infiltration or fibrosis) layers of the urethra, allowing better understanding of the pathogenesis of the disease and monitoring of therapy.

Keywords: urethral pain syndrome (UPS), cross-polarization optical coherence tomography (CP OCT), diagnosis of UPS, connective tissue matrix of the urethra, analysis of the microbiota of urethral tissues