Abstract
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.
Highlights
Pre-clinical studies have shown that spinal cord epidural stimulation at the level of pelvic and pudendal nerve inputs/outputs (L5-S1) alters storage and/or emptying functions of both the bladder and bowel
Bladder and bowel health are among the most common reasons for re-hospitalization after spinal cord injury (SCI) and are a major source of morbidity. Deficits develop in both storage and emptying dynamics, leading to incontinence and retention[3]
Data sets collected from intact females (IF; n = 7/11), intact males (IM; n = 12/12), transected females (STxF; n = 8/9), and transected males (STxM; n = 9/12) were analyzed according to sex, injury, and stimulation parameters
Summary
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. Novel stimulation focused on neuromodulation including[8]: electrical stimulation of the tibial9–12, saphenous[13,14], pudendal nerves[15,16], and the dorsal genital nerve[17,18]; electrical stimulation of the sacral nerves[19,20]; sacral anterior root stimulation (SARS) combined with posterior root r hizotomy[21–23]; and the recently described laproscopic neuroprosthesis implantation[24] Surgical methods, such as bladder augmentation or c olostomy[4], are reserved for those patients in which all other treatment strategies have failed to produce sufficient benefit. Initially targeted for standing and s tepping[31], many other benefits have been uncovered, including multiple autonomic functions, suggesting that scES can improve off-target function via interaction with spinal circuits that extend across numerous levels of the spinal cord These effects are consistent with a recent study utilizing transcutaneous stimulation to improve bladder function[32]. Several preliminary scES clinical case reports showing benefits of directly targeting spinal circuitries mediating bladder and bowel function prompted mapping studies for identification of spatial specificity and optimal parameters for achieving storage and emptying for both lower urinary tract (LUT) and anorectal function in rodent models that have been used extensively for pre-clinical studies of S CI33
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