Bladder and bowel responses to lumbosacral epidural stimulation in uninjured and transected anesthetized rats

Abstract

Spinal cord epidural stimulation (scES) mapping at L5-S1 was performed to identify parameters for bladder and bowel inhibition and/or contraction. Using spinally intact and chronic transected rats of both sexes in acute urethane-anesthetized terminal preparations, scES was systematically applied using a modified Specify 5–6–5 (Medtronic) electrode during bladder filling/emptying cycles while recording bladder and colorectal pressures and external urethral and anal sphincter electromyography activity. The results indicate frequency-dependent effects on void volume, micturition, bowel peristalsis, and sphincter activity just above visualized movement threshold intensities that differed depending upon neurological intactness, with some sex-dependent differences. Thereafter, a custom-designed miniature 15-electrode array designed for greater selectivity was tested and exhibited the same frequency-dependent urinary effects over a much smaller surface area without any concurrent movements. Thus, select activation of autonomic nervous system circuitries with scES is a promising neuromodulation approach for expedient translation to individuals with SCI and potentially other neurologic disorders.

Thoracolumbar epidural stimulation effects on bladder and bowel function in uninjured and chronic transected anesthetized rats

“…The proportion of animals in OI per group is consistent with our previous study 33 , whereby the bladder pressure recordings indicate oscillations around fluid being pumped in and leaking out at capacity. This pressure data could not be quantified in the same way as the other animals and so was analyzed separately for: AUC, mean pressure, maximum pressure, and minimum pressure (Fig.…”

“…The average of five baseline void volumes per rat collected after consistent fill-void cycle patterns were established (filling at a pump speed of 0.25 cc/min) were similar (p > 0.05) for intact females (0.61 cc, SEM = 0.09), intact males (0.52 cc, SEM = 0.05), transected females (0.52 cc, SEM = 0.11), and transected males (0.47 cc, SEM = 0.02). As established previously 33 , a subset of SCI rats (100% of males and 37.5% of females) displayed an overflow incontinence (OI) phenotype whereby upon reaching capacity, small drops of urine would leak upon small detrusor pressure increases rather than expelled as an intermittent stream with a reflex bladder contraction.…”

“…For data reduction, per our previously published study 33 , mapping parameters were grouped according to low (5 and 10 Hz) versus high (30, 45, and 60 Hz) frequency and below versus above visualized movement stimulus intensity threshold (VisMvt; 50, 75, 100 µA and 150 and 300 µA, respectively). These four groupings presented as four quadrants (Q1–Q4) on heat maps for each functional outcome and analysis using the following designations: (Q1) low frequency, below VisMvt; (Q2) high frequency, below VisMvt; (Q3) high frequency; above VisMvt; and (Q4) low frequency, above VisMvt.…”

“…Previous data from our laboratory obtained from acute terminal studies in non-injured and chronic-transected male and female urethane-anesthetized adult rats indicated numerous scES-induced effects on bladder and bowel functions within the lumbosacral region of the spinal cord (L5-S1; level of inputs/outputs of the pelvic and pudendal nerves) 33 . For the current experiments, the thoracolumbar region of the spinal cord was targeted (T13-L2; level of inputs/outputs of the hypogastric nerve).…”

“…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 SCI 33 .…”