Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, USA.
Physical Medicine and Rehabilitation Department, MetroHealth Rehabilitation Institute of Ohio, Cleveland, OH, USA.
Sci Rep. 2022 Feb 8;12(1):2137. doi: 10.1038/s41598-022-06011-2.
Pre-clinical studies have shown that spinal cord epidural stimulation (scES) at the level of pelvic and pudendal nerve inputs/outputs (L5-S1) alters storage and/or emptying functions of both the bladder and bowel. The current mapping experiments were conducted to investigate scES efficacy at the level of hypogastric nerve inputs/outputs (T13-L2) in male and female rats under urethane anesthesia. As found with L5-S1 scES, T13-L2 scES at select frequencies and intensities of stimulation produced an increase in inter-contraction interval (ICI) in non-injured female rats but a short-latency void in chronic T9 transected rats, as well as reduced rectal activity in all groups. However, the detrusor pressure during the lengthened ICI (i.e., urinary hold) remained at a low pressure and was not elevated as seen with L5-S1 scES, an effect that's critical for translation to the clinic as high fill pressures can damage the kidneys. Furthermore, T13-L2 scES was shown to stimulate voiding post-transection by increasing bladder activity while also directly inhibiting the external urethral sphincter, a pattern necessary to overcome detrusor-sphincter dyssynergia. Additionally, select scES parameters at T13-L2 also increased distal colon activity in all groups. Together, the current findings suggest that optimization of scES for bladder and bowel will likely require multiple electrode cohorts at different locations that target circuitries coordinating sympathetic, parasympathetic and somatic outputs.
临床前研究表明,脊髓硬膜外刺激(scES)在骨盆和阴部神经输入/输出(L5-S1)水平改变了膀胱和肠道的储存和/或排空功能。目前的映射实验旨在研究在雄性和雌性大鼠在氨基甲酸乙酯麻醉下,在腹下神经输入/输出(T13-L2)水平进行 scES 的疗效。与 L5-S1 scES 一样,在选择的频率和刺激强度下,T13-L2 scES 在未受伤的雌性大鼠中增加了非收缩间隔(ICI),但在慢性 T9 横断大鼠中引起了短潜伏期排空,以及所有组的直肠活动减少。然而,在延长的 ICI 期间(即,尿潴留),逼尿肌压力保持在低压力,与 L5-S1 scES 不同,这对于转化为临床非常重要,因为高填充压力会损害肾脏。此外,T13-L2 scES 被证明通过增加膀胱活动来刺激横断后排空,同时直接抑制尿道外括约肌,这是克服逼尿肌-括约肌协同失调所必需的模式。此外,T13-L2 的选择 scES 参数也增加了所有组的远端结肠活动。总之,目前的研究结果表明,优化膀胱和肠道的 scES 可能需要在不同位置使用多个电极队列,以针对协调交感神经、副交感神经和躯体输出的电路。