Results provide evidence for the location of TRPV4 in human bladder urothelium. TRPV4 is molecularly connected to adherence junctions on the urothelial cell membrane. TRPV4 coupling to a rigid intracellular and intercellular structural network would agree with the hypothesis that TRPV4 can be activated by bladder stretch.

This study reveals an important role for chondroitin sulfate in bladder barrier function. Therapies aiming at restoring the luminal glycosaminoglycan layer in pathological conditions such as bladder pain syndrome/interstitial cystitis are based on a sound principle.

ObjectivesThis review describes the evidence from established and experimental therapies that use electrical nerve stimulation to treat lower urinary tract dysfunction.MethodsClinical studies on established treatments such as percutaneous posterior tibial nerve stimulation (P-PTNS), transcutaneous electrical nerve stimulation (TENS), sacral nerve stimulation (SNS) and sacral anterior root stimulation (SARS) are evaluated. In addition, clinical evidence from experimental therapies such as dorsal genital nerve (DGN) stimulation, pudendal nerve stimulation, magnetic nerve stimulation and ankle implants for tibial nerve stimulation are evaluated.ResultsSNS and P-PTNS have been investigated with high-quality studies that have shown proven efficacy for the treatment for overactive bladder (OAB). SARS has proven evidence-based efficacy in spinal cord patients and increases the quality of life. TENS seems inferior to other OAB treatments such as SNS and P-PTNS but is noninvasive and applicable for ambulant therapy. Results from studies on experimental therapies such as pudendal nerve stimulation seem promising but need larger study cohorts to prove efficacy.ConclusionNeurostimulation therapies have proven efficacy for bladder dysfunction in patients who are refractory to other therapies.SignificanceRefinement of neurostimulation therapies is possible. The aim should be to make the treatments less invasive, more durable and more effective for the treatment of lower urinary tract dysfunction.

After 9 years of clinical experience, we demonstrated that implant driven PTNS with the Urgent-SQ™ is a safe therapy for OAB. The implant has a long lifespan and is well tolerated by patients.

Normal bladder filling sensation is dependent on multiple interacting mechanoreceptors and signalling pathways. Research efforts need to focus on how these pathways and receptors interact to fully understand normal bladder filling signalling.