Effects of on-demand and early neuromodulation interventions on bladder function after spinal cord injury

PROJECT SUMMARY The prevalence of spinal cord injury (SCI) in the United States exceeds 350,000 individuals, with approximately 18,000 new injuries each year. Nearly everyone with SCI loses voluntary control of their bladder, and improving bladder care is emphasized by people living with SCI as a critically important need. This is in large part because current clinical management techniques, including catheterization and medications, fall short in addressing the complexities of bladder dysfunction after SCI. Epidural spinal cord stimulation (SCS) over the sacral spinal cord is a promising new approach and may be able to activate spinal reflexes and restore lower urinary tract control. While surgical access to relevant lower urinary tract nerves in humans is difficult, SCS offers a clinically established approach to activating these nerves on the surface of the spinal cord. Our preliminary findings suggest that SCS can evoke both micturition and continence reflexes in anesthetized cats with intact spinal cords and also after acute spinal transection. The challenge now is to evaluate whether it is possible to elicit functional changes in the lower urinary tract after chronic SCI where permanent maladaptive changes occur in the neural control of the bladder. We propose to use SCS in two innovative ways to regain bladder function following SCI. In Aim 1 we will evaluate if both micturition and continence can be evoked in cats with chronic SCI by using multiple stimulation frequencies. A closed-loop control system will use continuous bladder pressure measurements acquired through an implanted telemetry system to control continence and micturition on demand. In Aim 2, we will investigate an early intervention strategy to prevent maladaptive changes in the neural control of the bladder that are the primary drivers of bladder overactivity. We will deliver long duration (~23 hours/day) SCS that begins immediately after SCI for up to 4 weeks, and measure the effects on reflexive bladder contractions. This approach could slow or prevent bladder overactivity from occurring. The data generated from this proposal will de-risk the future studies that will be aimed towards more comprehensively evaluating optimal stimulation parameters in animal studies, but will also provide evidence to rapidly evaluate sacral SCS in people with SCI.