Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States.
Joint Department of Biomedical Engineering, Medical College of Wisconsin, Marquette University, Milwaukee, Wisconsin, United States.
Am J Physiol Renal Physiol. 2023 Dec 1;325(6):F757-F769. doi: 10.1152/ajprenal.00123.2023. Epub 2023 Oct 5.
The stimulation paradigm for sacral neuromodulation has remained largely unchanged since its inception. We sought to determine, in rats, whether stimulation-induced increases in bladder capacity correlated with the proportion of sensory pudendal (PudS) neurons at each stimulated location (L6, S1). If supported, this finding could guide the choice of stimulation side (left/right) and level (S2, S3, S4) in humans. Unexpectedly, we observed that acute stimulation at clinically relevant (low) amplitudes [1-1.5 × motor threshold (T)], did not increase bladder capacity, regardless of stimulus location (L6 or S1). More importantly for the ability to test our hypothesis, there was little anatomic variation, and S1 infrequently contributed nerve fibers to the PudS nerve. During mapping studies we noticed that large increases in PudS nerve activation occurred at amplitudes exceeding 2T. Thus, additional cystometric studies were conducted, this time with stimulation of the L6-S1 trunk, to examine further the relationship between stimulation amplitude and cystometric parameters. Stimulation at 1T to 6T evoked increases in bladder capacity and decreases in voiding efficiency that mirrored those produced by PudS nerve stimulation. Many animal studies involving electrical stimulation of nerves of the lower urinary tract use stimulation amplitudes that exceed those used clinically (∼1T). Our results confirm that high amplitudes generate immediate changes in cystometric parameters; however, the relationship to low-amplitude chronic stimulation in humans remains unclear. Additional studies are needed to understand changes that occur with chronic stimulation, how these changes relate to therapeutic outcomes, and the contribution of specific nerve fibers to these changes. Acute low-amplitude electrical stimulation of sacral nerve (sacral neuromodulation) did not increase bladder capacity in anesthetized CD, obese-prone, or obese-resistant rats. Increasing stimulation amplitude correlated with increases in bladder capacity and pudendal sensory nerve recruitment. It is unclear how the high-amplitude acute stimulation that is commonly used in animal experiments to generate immediate effects compares mechanistically to the chronic low-amplitude stimulation used clinically.
骶神经调节的刺激模式自出现以来基本保持不变。我们试图在大鼠中确定，刺激引起的膀胱容量增加是否与每个刺激部位（L6、S1）的感觉阴部（PudS）神经元的比例相关。如果得到支持，这一发现可以指导在人类中选择刺激侧（左/右）和水平（S2、S3、S4）。出乎意料的是，我们观察到，在临床相关（低）幅度[1-1.5×运动阈值（T）]下进行急性刺激，无论刺激部位（L6 或 S1）如何，均不会增加膀胱容量。对我们假设的检验能力而言，更重要的是，解剖变异很小，S1 很少有神经纤维贡献给 PudS 神经。在映射研究中，我们注意到在超过 2T 的幅度下，PudS 神经激活会大幅增加。因此，进行了额外的膀胱测压研究，这次是刺激 L6-S1 干，以进一步研究刺激幅度和膀胱测压参数之间的关系。在 1T 至 6T 的刺激下，膀胱容量增加，排尿效率降低，与 PudS 神经刺激产生的效果相似。许多涉及下尿路神经电刺激的动物研究使用的刺激幅度超过临床使用的幅度（约 1T）。我们的结果证实，高幅度会立即改变膀胱测压参数；然而，在人类中，与低幅度慢性刺激的关系尚不清楚。需要进一步研究以了解慢性刺激引起的变化，这些变化与治疗结果的关系，以及特定神经纤维对这些变化的贡献。急性低幅度骶神经电刺激（骶神经调节）未增加麻醉 CD、肥胖易感或肥胖抵抗大鼠的膀胱容量。增加刺激幅度与膀胱容量增加和阴部感觉神经募集相关。目前尚不清楚，在动物实验中，通常用于产生即时效果的高幅度急性刺激在机制上与临床上使用的慢性低幅度刺激有何不同。
