Afferent stimulation for exciting reflex micturition circuits .

摘要

Individuals with bladder voiding dysfunction who do not respond to standard treatments have limited options. Activation of reflex micturition through sensory pudendal nerve stimulation provides a means to empty the bladder. Little is known about the mechanisms behind this pathway, and afferent-mediated voiding is less than results obtained by direct sacral root drive. This project investigated the neurophysiology of reflex bladder activation and evaluated new stimulus patterns and locations to improve afferent excitation of spinal circuits that produce bladder excitation and voiding.;The use of novel physiologically based burst-patterned pudendal nerve stimuli significantly increased bladder contractions over currently used continuous stimulation (52.0 +/- 44.5%, p 0.004). Bladder excitation was effective at lower frequencies (1--10 pulses at 100--200 Hz repeated at 0.5--1 Hz) and higher frequencies (1--2 pulses at 200 Hz repeated at 20--33 Hz).;Stimulating with lower and higher frequencies at different urethral locations before and after spinalization suggested two neural pathways for exciting reflex bladder contractions: a supra-sacral circuit initiated in the proximal urethra that responds to both frequency ranges and a sacral circuit initiated in the distal urethra that only responds to higher frequency stimuli. Subject pathology will dictate which circuit is the neuroprosthetic target.;Stimulation with fine wire electrodes in the urethral wall excited the proximal urethra initiated circuit with minimal sphincter recruitment and evoked greater voiding efficiencies for the use of lower frequency burst-patterned stimuli (72.7 +/- 27.6%) than other stimulus patterns on the same electrodes (p > 0.08) or any stimulus patterns on electrodes with urethral closure (p 0.01). This pre-clinical translational study extended the functional proxy of bladder excitation to an effective functional voiding output.;This work increases the knowledge-base of lower urinary tract neurophysiology, indicating more effective stimulation strategies and locations. This research will advance peripheral nerve-based neuroprostheses for bladder excitation, improving functional outputs and matching interventions to the patient population.