Sacral Neuromodulation for Lower Urinary Tract and Bowel Dysfunction in Animal Models: A Systematic Review With Focus on Stimulation Parameter Selection

Abstract

Objective: Conventional sacral neuromodulation (SNM) has shown to be an effective treatment for lower urinary tract and bowel dysfunction, but improvements of clinical outcome are still feasible. Currently, in preclinical research, new stimulation parameters are being investigated to achieve better and longer effects. This systematic review summarizes the status of SNM stimulation parameters and its effect on urinary tract and bowel dysfunction in preclinical research. Materials and Methods: The literature search was conducted using three databases: Ovid (Medline, Embase) and PubMed. Articles were included if they reported on stimulation parameters in animal studies for lower urinary tract or bowel dysfunction as a primary outcome. Methodological quality assessment was performed using the SYRCLE Risk of Bias (RoB) tool for animal studies. Results: Twenty-two articles were eligible for this systematic review and various aspects of stimulation parameters were included: frequency, intensity, pulse width, stimulation signal, timing of stimulation, and unilateral vs. bilateral stimulation. In general, all experimental studies reported an acute effect of SNM on urinary tract or bowel dysfunction, whereas at the same time, various stimulation settings were used. Conclusions: The results of this systematic review indicate that SNM has a positive therapeutic effect on lower urinary tract and bowel dysfunction. Using low-frequency-SNM, high-frequency-SNM, bilateral SNM, and higher pulse widths showed beneficial effects on storage and evacuation dysfunction in animal studies. An increased variability of stimulation parameters may serve as a basis for future improvement of the effect of SNM in patients suffering from urinary tract or bowel dysfunction.

Sacral neuromodulation remote programming in patients with refractory lower urinary tract dysfunction: China’s experience during the COVID-19 pandemic

“…However, Chinese experts have a conservative attitude toward secondary surgical intervention, believing that it must be conducted only in cases where combined oral medications and repeated adjustments of stimulation parameters have proven ineffective (15,16). A recent meta-analysis described the efficacy of different combinations of stimulus parameters on LUTD, affirming the importance of programming to ensure the efficacy of SNM (17). Therefore, regular programming is an important means of ensuring a stable curative effect and reducing the probability of refractory patients with LUTD requiring second surgical interventions.…”

Efficacy and Safety of Sacral Neuromodulation by Converting Constant Frequency Stimulation Into Variable Frequency Stimulation in Patients With Detrusor Overactivity and Impaired Contractility: A Single-Center Prospective Study

“…Therefore, management of DOIC using pharmacotherapy can be very challenging. 16,17 Recent studies have reported satisfactory success rates for SNM in patients with either DO or impaired contractility, but postoperative program control has certain limitations. 18,19 For example, studies have shown that the improvement of patients' clinical symptoms is mainly achieved by adjustment of SNM frequency.…”

Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies

“…Preclinical models are necessary for many steps in the development of medical devices, from answering basic science questions to testing the design engineering and performance prior to use in humans (see Section 9). Preclinical testing with the use of animal models allows for hypothesis testing, mapping neural pathways and exploring the therapeutic potential of nerve stimulation ( Swanson et al, 2012 ; Frasch et al, 2016 ; Gierthmuehlen and Plachta, 2016 ; Douven et al, 2020 ). Animal models also allow for invasive testing during the development process that is not feasible in humans, including adjustment of device size, fit and design, and for optimization of settings such as frequency, timing, duration, and location of treatment in preparation for clinical studies ( Figure 12 ).…”