Redefining bladder sympathetic Innervation with three-dimensional image reconstruction

The primary goals of functional bladder reconstruction following spinal cord injury are to restore voiding power and reduce voiding resistance. The sympathetic nerve is one of the critical constraints within the reduce voiding resistance. In this paper, we sought to generate a three-dimensional (3D) reconstruction of bladder-innervating sympathetic nervous tissue, utilizing histopathological samples derived from male and female cadavers. Bladder tissue samples were collected from four formalin-fixed cadavers (two male, two female). After preparing axial cross-sections of the bladder at 4 mm intervals and staining them with Tyrosine-hydroxylase, the distance between the sympathetic nerve site and lumen surface of the bladder, the number of sympathetic nerve sites, and the sympathetic nerve density were measured. The densest sympathetic innervation was observed at the bladder neck (female specimen) and the prostatic urethra (male specimen). For both sexes, nerve density at all levels of the proximal urethra and bladder neck was significantly greater in the posterior region compared to the anterior: in females, 2.51 ± 0.95 vs 1.11 ± 0.21 nerves per mm² (p < 0.001); in males, 2.88 ± 0.81 vs 1.49 ± 0.56 nerves per mm² (p < 0.001). The study found no statistically significant differences in nerve-to-lumen distances across multiple anatomical regions in either males or females, despite some numerical variations. In conclusion, novel 3D reconstruction of the bladder sympathetic nerve distribution is feasible, and this approach may refine our current understanding of human bladder innervation. In addition, it presents a sympathetic nerve map of the bladder, which may serve as a preliminary anatomical basis to explore the potential of nerve-targeting radiofrequency therapies for bladder dysfunction following SCI.