Urological dysfunctions are ranked as a top priority by the spinal cord injury (SCI) population. Traditional methods that include pharmacotherapy, non-electrical devices such as catheters and surgical procedures when deemed necessary target management but do not replace or restore control of the lower urinary tract. It is hypothesized that spinal cord epidural stimulation (scES) has clinical effectiveness for restoration of voluntary and reflex control of the lower urinary tract.  The objective of the current functional mapping pre-clinical animal study is to identify scES configurations (location, amplitude and frequency) that can promote optimal neural control of urine storage (adequate bladder capacity at safe pressures without incontinence) and/or sufficient controlled emptying (high voiding efficiency at safe leak point pressures).

Mapping at L5-S1 with scES was performed in 20 female Wistar rats to identify parameters for bladder storage and/or emptying. The L5-S1 spinal cord was targeted first as this level has inputs/outputs of pelvic (parasympathetic) and pudendal (somatic) nerves supplying the pelvic visceral organs (equivalent to S2-4 in humans). Using spinally intact (n=10) and chronic complete transected rats (T9 spinal level; n=10) in an acute urethane-anesthetized terminal preparation, scES was systematically applied over a wide surface area with a modified Medtronic 5-6-5 electrode during bladder filling/emptying cycles while recording bladder pressures along with external urethral sphincter EMG activity. Note that a power analysis was performed on the expected group means based on literature from similar studies showing that a sample size of 8 per group would achieve a significant difference between the groups with a power of 99% (2 rats added for a total of 10/group to account for possible attrition rates based on complications). In addition, a specially designed rodent-sized miniature 15-electrode array was then used in five more spinally intact female rats to assess the optimal responsive location within the L5-S1 region.

With scES on, all spinally intact rat cystometrograms show a steep rise in bladder pressure when capacity is reached and a subsequent overflow incontinence, with a contraction and void only upon offset of scES. In contrast, animals with a chronic spinal transection void immediately at the onset of scES. Intensity parameters in the 300-500 µA range and frequencies in the 30-60 Hz range at L5-S1 were necessary for holding in the intact rats and for an immediate void in the transected group. Although 100% of the intact rats had consistent fill/void cycles, 40% of the transected group had overflow incontinence without any contractions, although scES was still effective in inducing a void. Note that the EMG pattern during the scES-induced hold was reflective of guarding-like activity and had the typical consistent phasic bursting pattern during emptying. In contrast, the transected group of rats had intermittent patterns of high activity consistent with detrusor sphincter dyssynergia. Furthermore, the optimal urinary system effects were found with the miniature 15-electrode array to be located at L6. The scES parameters were at the same frequencies but intensities were at significantly lower levels (50-80 µA) with minimal concomitant motor responses.

The results indicate frequency and intensity dependent effects on bladder capacity, micturition, and sphincter EMG activity that differed depending upon neurological intactness. These findings are consistent with known plasticity of the lower urinary tract segmental circuitry in the intact versus the chronic transection model.

Epidural stimulation for activating spinal circuits involved with urinary function is a promising neuromodulation approach for expedient translation to individuals with SCI.