Electrical stimulation of the lower urinary tract (LUT) is typically used to assess current perception thresholds and sensory evoked potentials to investigate LUT afferent function. However, changing bladder volume during measurement may influence the outcome. We therefore aimed to quantify urine production during LUT electrical stimulation using different stimulation frequencies. We hypothesized that electrical stimulation of the LUT would increase urine production per time compared to baseline values. Assuming location-specific innervations in the LUT, urine production per time was expected to be higher during electrical stimulation at the trigone compared to the other locations [1]. In addition, mean urine production per time was predicted to be bigger when stimulating with a higher frequency (respectively stimulation intensity) compared to a lower frequency (respectively lower stimulation intensity).

After local ethics committee approval, 89 healthy controls (mean age: females (n=39): 23.4±3.4 years, males (n=50): 24.3±3.9 years) were considered for the analysis. All of the subjects completed a 3-day bladder diary. LUT stimulation site was randomly assigned: bladder dome (n=20), trigone (n=20), proximal urethra (n=20), membraneous urethra (n=10, males only), and distal urethra (n=19). After catheter placement the bladder was emptied and refilled with 60mL of contrast medium. Current perception threshold assessment followed by electrical stimulation was applied at two separate visits with a 14Ch custom-made catheter using three different frequencies (500 stimuli - stimulation frequency 0.5Hz (~16.7min), 1.1Hz (~7.6min), 1.6Hz (~5.2min)) in random order. After each stimulation session, the bladder was emptied again and volumes were recorded. In order to control for different stimulation times, urine production per time was analyzed. Linear mixed effects modeling was used to estimate the impact of specific variables on bladder volume increase, i.e. urine production per time, during electrical stimulation in the LUT.

The average amount of daily fluid intake was 2287±882mL for females and 2319±1101mL for males. Compared to average natural diuresis over 24 hours as assessed by bladder diary (1.4±0.6mL/min for females and 1.3±0.8mL/min for males), urine production per time increased (p<0.001) in average to 11.9±7.5mL/min in females and 9.2±8.2mL/min in males during electrical stimulation. With 0.5Hz stimulation, urine production per time increased by factor 6.5 compared to the bladder diary values, while it increased by factor 11.6 when stimulating with 1.6Hz. Stimulation frequency (p<0.001), stimulation order (p=0.002), and stimulation intensity (p=0.021) had a significant influence on urine production per time and was different between genders (p=0.024), while stimulation location and visit had no statistical significant influence.

The results showed that electrical stimulation in the LUT significantly increased urine production per time with a bigger impact of higher frequencies and stimulation intensities. We think that a greater energy input to the afferent nerves of the lower urinary tract enhances the observed effect. In contrary to our hypothesis, the linear mixed effects model did not reveal a significant effect of stimulation site on urine production per time. We assume that this increase in diuresis is mainly centrally regulated while peripheral innervation plays a minor role.

This is the first study in healthy young subjects that investigated a potential relationship between electrical LUT stimulation and urine output. The finding of increased diuresis during LUT electrical stimulation might not only be relevant for methodological aspects in the assessment of LUT afferent function but also for patients with impaired urine output. It is a highly interesting and relevant observation from a physiological but also clinical point of view. Yet, there is no clear concept or knowledge on the functional interrelation of LUT electrical stimulation and urine production in the kidneys. Although the exact mechanism is unknown, we assume involvement of autonomic circuits including the spinal and supraspinal control centres.

Spradling, K., Khoyilar, C., Abedi, G., Okhunov, Z., Wikenheiser, J., Yoon, R., et al. (2015). Redefining the Autonomic Nerve Distribution of the Bladder Using 3-Dimensional Image Reconstruction. J Urol, 194(6), 1661-1667.