Toward Novel Targeted Therapy for Overactive Bladder: A Cadaver Study Identifying Critical Autonomic Nerve Structures.

Introduction and objectives: Targeted radiofrequency (RF) therapy is a promising treatment for overactive bladder (OAB), aiming to modulate autonomic nerve pathways for symptom control. This cadaveric study focuses on identifying areas of high nerve density in the bladder and corresponding vaginal wall (AVW) to support RF use in a minimally invasive fashion throughout the anterior vaginal wall.

Methods: AVW samples were obtained from two cadaveric specimens (T1 & T2). Hematoxylin and eosin (H&E) staining was employed to assess anatomical structures, while S100 immunohistochemistry was used to visualize nerve distribution. Nerve size and density across the anterior and posterior bladder walls, along with the attached anterior vaginal wall were quantified using image analysis software. Statistical analyses, including one-way ANOVA and pairwise t-tests, were conducted to assess differences across different regions in the posterior bladder wall divided into: "Towards Vagina," "High nerve density" (HND), and "Towards Bladder" at 0-2.4 mm, 4.8-7.2 mm, and 7.2-9.6 mm in depth from the vaginal surface, respectively.

Results: H&E staining confirmed intact anatomy. S100 staining revealed areas of higher nerve density at the regions associated with posterior bladder wall compared to the anterior wall, especially at HND targeted at 4.8-7.2 mm deep from the vaginal surface. ANOVA revealed significant differences in nerve size (p = 0.0017 in T1, p = 0.0006 in T2) and density (p = 0.036 in T1, p = 0.0007 in T2) in the HND region compared to those of the other regions. Similarly, pairwise t-tests indicated statistically significant differences between the HND region and any other region in the posterior wall. The HND zone consistently displayed the largest nerves and highest density across both specimens.

Conclusions: This study highlights the importance of the HND zone, as a critical target for RF therapy and other neuromodulation-based management in OAB treatment. The identification of this high-innervation zone guides the precise application of RF energy and supports the use of targeted RF therapy delivered through the anterior vaginal wall, potentially improving therapeutic outcomes with a minimally invasive modality.