Potential applications of low-energy shock waves in functional urology

Despite the success in clinical application, the exact mechanism of shock wave therapy remains unknown. We hypothesized that shock wave therapy induces the ingrowth of neovascularization and improves blood supply to the tissues. The purpose of this study was to investigate the effect of shock wave therapy on neovascularization at the tendon-bone junction. Fifty New Zealand white rabbits with body weight ranging from 2.5 to 3.5 kg were used in this study. The right limb (the study side) received shock wave therapy to the Achilles tendon near the insertion to bone. The left limb (the control side) received no shock wave therapy. Biopsies of the tendon-bone junction were performed in 0, 1, 4, 8 and 12 weeks. The number of neo-vessels was examined microscopically with hematoxylin-eosin stain. Neovascularization was confirmed by the angiogenic markers including vessel endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expressions and endothelial cell proliferation determined by proliferating cell nuclear antigen (PCNA) expression examined microscopically with immunohistochemical stains. The results showed that shock wave therapy produced a significantly higher number of neo-vessels and angiogenesis-related markers including eNOS, VEGF and PCNA than the control without shock wave treatment. The eNOS and VEGF began to rise in as early as one week and remained high for 8 weeks, then declined at 12 weeks; whereas the increases of PCNA and neo-vessels began at 4 weeks and persisted for 12 weeks. In conclusion, shock wave therapy induces the ingrowth of neovascularization associated with early release of angiogenesis-related markers at the Achilles tendon-bone junction in rabbits. The neovascularization may play a role to improve blood supply and tissue regeneration at the tendon-bone junction.

Botulinum neurotoxin type A (BoNT/A) is effective in the treatment of intractable detrusor overactivity (DO). In addition to its known inhibitory effect on presynaptic release of acetylcholine by motor terminals, there is increasing evidence that BoNT/A may affect sensory fibers. We investigated a possible effect of BoNT/A on human bladder afferent mechanisms by studying the sensory receptors P2X3 and TRPV1 in biopsies from patients with neurogenic or idiopathic DO. A total of 38 patients (22 with neurogenic DO, 16 with idiopathic DO) with intractable DO were treated with intradetrusor BoNT/A, and bladder biopsies were taken at 4 and 16 weeks. Urodynamics and voiding diary were also recorded. Specimens were studied immunohistochemically for P2X3, TRPV1 and the pan-neuronal marker PGP9.5, in comparison with controls. P2X3-immunoreactive and TRPV1-immunoreactive (-IR) fibers were decreased at 4 weeks after BoNT/A, and more significantly at 16 weeks (paired t test p=0.0004 and p=0.0008, respectively), when significant improvements were observed in clinical and urodynamic parameters. P2X3-IR fiber decrease was significantly correlated with reduction of urgency episodes at 4 and 16 weeks (p=0.0013 at 4 weeks and p=0.02 at 16 weeks), but not maximum cystometric capacity or detrusor pressures. TRPV1-IR fiber decrease showed a similar trend. PGP9.5-IR suburothelial fibers remained unchanged after treatment at both followups (p=0.85 and p=0.21 at 4 and 16 weeks, respectively). Urothelial cell P2X3-IR and TRPV1-IR also appeared unchanged. Decreased levels of sensory receptors P2X3 and/or TRPV1 may contribute to the clinical effect of BoNT/A in detrusor overactivity.