Quantification of effectiveness of bilateral and unilateral neuromodulation in the rat bladder rhythmic contraction model

Abstract

BackgroundUsing the isovolumetric bladder rhythmic contraction (BRC) model in anesthetized rats, we have quantified the responsiveness to unilateral and bilateral stimulation of the L6 spinal nerve (SN) and characterized the relationship between stimulus intensity and inhibition of the bladder micturition reflex.MethodsA wire electrode was placed under either one or both of the L6 SN roots. A cannula was placed into the bladder via the urethra and the urethra was ligated. Saline infusion induced BRC.ResultsAt motor threshold (Tmot) intensity, SN stimulation of both roots (10 Hz) for 10 min reduced bladder contraction frequency from 0.63 ± 0.04 to 0.17 ± 0.09 contractions per min (26 ± 14% of baseline control; n = 10, p < 0.05). However, the same intensity of unilateral stimulation (n = 15) or sequential stimulation of both SNs (e.g. 5 min per side alternatively for a total of 10 min or 20 min) was less efficacious. The greater sensitivity to bilateral stimulation is not dependent upon precise bilateral timing of the stimulation pulses. Bilateral stimulation also produced both acute and prolonged- inhibition on bladder contractions in a stimulation intensity dependent fashion.ConclusionsUsing the bladder rhythmic contraction model, bilateral stimulation was more effective than unilateral stimulation of the SN. Clinical testing should be conducted to further compare efficacies of unilateral and bilateral stimulation. Bilateral stimulation may allow the use of lower stimulation intensities to achieve higher efficacy for neurostimulation therapies on urinary tract control.

Optimization of Neuromodulation for Bladder Control in a Rat Cystitis Model

“…This is in agreement with the isovolumetric rat model which tested the effect of SNS on the micturition reflex in the normal rats and demonstrated a narrower range of bladder inhibition with 10 Hz only, but not 1‐ or 20‐Hz stimulation . In addition, in both isovolumetric and cystometry (present study) measures, the magnitude of the inhibitory action was directly proportional to the applied current (stimulus intensity).…”

A Chronic, Conscious Large Animal Platform to Quantify Therapeutic Effects of Sacral Neuromodulation on Bladder Function

“…SNM was delivered bilaterally to the sacral nerves, in contrast to unilateral S3 targeting in clinical use, but this was consistent with preclinical results using isovolumetric assays in the normal rodent. 26 SNM was applied acutely in our model with sheep receiving about 10 to 30 minutes of stimulation while in patients therapy is delivered chronically. In this initial test there was likely a notable difference in stimulation amplitude relative to MT (about 3.5-fold) compared to human use, which is applied at a submotor threshold.…”

Electrical Stimulation of the Spinal Dorsal Root Inhibits Reflex Bladder Contraction and External Urethra Sphincter Activity: Is This How Sacral Neuromodulation Works?

“…In complete SCI patients, bilateral SNM could positively impact micturition [13], which was once proved to be not effective with unilateral implantation [17]. In 2 animal tests, bilateral SNM was proved to be more effective in reducing the bladder contractions (per minutes) than unilateral stimulation with the same parameter [18,19]. Bilateral stimulation was assumed to be more effective because it could theoretically activate more afferent nerve fibers projected to the SC as well as supraspinal centers, and consequently broke off total information of bladder extension.…”