Rat Animal Models for Evaluation of the Effects of Sacral and Peripheral Nerve Stimulation on Bladder Function

Neuromodulation, a therapeutic approach to the dysfunction of various organs, has proven effective in treating lower urinary tract dysfunctions. Despite its clinical success, the mechanisms underlying neuromodulation remain incompletely understood, emphasizing the need for standardized and reproducible animal models. Preclinical models of urinary bladder neuromodulation using sacral and peripheral nerve stimulation have been established for more than two decades; however, the existing literature provides limited methodological detail regarding the surgical procedures. This article offers a detailed description and visual representation of well-established techniques for sacral nerve stimulation. It also describes a modified approach to tibial nerve stimulation and introduces a novel bladder neuromodulation method using peroneal nerve stimulation in a rat model. The modified tibial nerve stimulation approach involves exposing and stimulating the tibial nerve at its origin, as a branch of the sciatic nerve, rather than at the medial ankle, as described in previous studies. Given the recent introduction of peroneal nerve stimulation for bladder neuromodulation in clinical practice, this article proposes a unique rat model to investigate its mechanisms in the control of lower urinary tract function. Step-by-step guidance for all three neuromodulation methods is outlined for nerve exposure, electrode placement, and verification of successful electrode placement based on characteristic motor responses. A representative example of the effect of peroneal nerve stimulation on bladder function in a rat model of acetic acid-induced bladder overactivity is included to demonstrate its applicability. This article presents a standardized, technically accessible protocol for studying neuromodulation mechanisms, including alterations in bladder sensory signaling, spinal and supraspinal regulatory pathways, optimization of stimulation parameters, and comparison of the efficacy of different stimulation targets.