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Background: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. Aim: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. Methods: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. Outcomes: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. Results: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. Outcomes: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. Results: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P <.001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P =.011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. Clinical Implications: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. Strengths and Limitations: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. Conclusions: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge. [ABSTRACT FROM AUTHOR]

Background Data are limited regarding fractional CO2 laser as a nonhormonal treatment for vestibular pain. Aim We sought to perform what is, to our knowledge, the first multisite prospective randomized, double-blind, sham-controlled clinical trial to assess the safety and efficacy of fractional CO2 laser treatment to the vestibule in women with vestibular pain. Methods Subjects (n  = 70) meeting inclusion/exclusion criteria at each of 3 sites were randomized 2:1 to active or sham (zero energy) fractional CO2 laser treatment using the vestibular probe (SmartXide2 V2LR - MonaLisa Touch, DEKA, Florence, Italy). Subjects in each treatment arm received 3 treatments 4 weeks apart. At the initial follow-up (week 12), subjects were unblinded and those initially assigned to sham started active treatment. Outcomes Outcome measures included changes from baseline in sexual activity diaries and scores for the Vulvoscopic Genital Tissue Appearance Scale (VGTA), vestibular cotton-tipped swab testing, McGill Pain Questionnaire, Female Sexual Function Index (FSFI), Female Sexual Distress Scale–Revised (FSDS-R), and the O'Leary-Sant voiding and pain indices, the Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI). Results After active treatment, VGTA scores significantly improved in 5 parameters. Pain associated with cotton-tipped swab testing was significantly reduced at weeks 4 through 16 (mean change from baseline −0.64 [95% CI, −0.79 to −0.50] and −1.31 [95% CI, −1.46 to −1.16], respectively). FSFI pain domain scores improved significantly at weeks 12 and 16 (mean change from baseline 0.925 [95% CI, 0.10-1.75] and 1.22 [95% CI, 0.40-2.05], respectively). FSFI total scores increased significantly at weeks 12 and 16 (mean change from baseline 6.24 [95% CI, 2.64-9.85] and 4.96 [95% CI, 1.36-8.57], respectively). FSDS-R scores decreased significantly at weeks 12 and 16 (mean change from baseline −5.84 [95% CI, −8.80 to −2.87] and −9.15 [95% CI, −12.11 to −6.18], respectively). ICSI scores decreased significantly at weeks 12 and 16 (mean change from baseline −0.91 [95% CI, −1.65 to −0.18] and −0.754 [95% CI, −1.49 to −0.02], respectively). ICPI scores decreased significantly at week 16 (mean change from baseline −0.99 [95% CI, −1.63 to −0.34]). In contrast, there were no significant changes in outcomes in the sham arm. No serious adverse events occurred. Clinical Implications Fractional CO2 laser treatment in women with vestibular pain resulted in improvement from baseline in multiple key outcome measures of vestibular health. Strengths and Limitations Strengths of the study were that it was a multisite prospective randomized double-blind, sham-controlled clinical trial that included multiple measures related to vestibular pain and sexual function. Limitations were the nonvalidated primary outcome measure and limited study cohort. Conclusion Fractional CO2 laser therapy is a safe and effective nonhormonal treatment for vestibular pain. [ABSTRACT FROM AUTHOR]

The article reviews several articles including "Insulin-like growth factor-1 gene delivery may enhance the proliferation of human corpus cavernosal smooth muscle cells," by M. Kim, E. C. Hwang, I. K. Pang and K. Park, "Sexual function in women with overactive bladder," by A. Zahariou, M. Karamouti, E. Tyligada and P. Papaioannou and "Age-related changes in kallikreinskinins system in rat corpus cavernosum," by T. Wang, Z. H. Wan, J. H. Liu, M. Y. Chen, R. B. Chen, W. M. Yang and Z. Q. Ye.

The article reviews studies related to medicine including "Role of the Nitric Oxide Pathway and the Endocannabinoid System in Neurogenic Relaxation of Corpus Cavernosum from Biliary Cirrhotic Rats," by M. Ghasemi, H. Sadeghipour et al, "Aging Causes Cytoplasmic Retention of MaxiK Channels in Rat Corporal Smooth Muscle Cells," by K. P. Davies, Y. Stanevsky, M. T. Tar et al and "Sexual Function and Dysfunction in Brazilian Patients With Obsessive-Compulsive Disorder and Social Anxiety Disorder," by L. F. Fontenelle, W. F. de Souza et al.

The article presents the study which investigates the effects of diabetes on vaginal blood flow, tissue morphology and the expression of key biochemical markers in the animal model. The researchers examined changes in the levels of arginase I, endothelial nitric oxide synthase and cGMP-dependent protein kinase by using streptozotocin-treated female rats. They concluded that diabetes may lead to multiple disruptions in sex steroid hormone synthesis, metabolism and action.