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Project

Spinal Cord Stimulation for Restoration of Bladder Function

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Our objective is to conduct in vivo studies of a novel approach to treat urinary incontinence and poor bladder emptying following SCI. Specifically, we will measure in rats the changes in bladder capacity and bladder voiding efficiency produced by epidural kilohertz-frequency spinal cord stimulation (KHF SCS). This novel mode of SCS is used successfully to treat chronic pain, but has not been considered for treatment of bladder dysfunction. There are strong parallels between the pathophysiology of chronic pain and bladder dysfunction following SCI, and we hypothesize that KHF SCS will be effective in treating bladder dysfunction. The outcome will establish the feasibility of restoring of bladder continence and emptying, and lay the foundation for subsequent translational studies in persons with SCI. SCI results in the inability to empty the bladder voluntarily, neurogenic detrusor overactivity (NDO), which is the involuntary contraction of the bladder at small volumes, and detrusor sphincter dyssynergia (DSD), in which the external urethral sphincter contracts, rather than relaxes, during bladder contraction. NDO and DSD cause incontinence, high-pressure or absent voiding, and large post-void residual volumes. These factors can result in ureteric reflux and obstruction, kidney infection, renal damage, autonomic dysreflexia with dangerous rises in blood pressure, incontinence that contributes to skin problems, and frequent urinary tract infections. Current approaches to treat bladder dysfunction in persons with SCI are inadequate, and novel approaches are required to restore continence with increased bladder capacity and provide predictable and efficient on-demand voiding. We will conduct preclinical in vivo experiments on an innovative approach using epidural SCS to restore bladder function. Aim 1 is to determine the parameters of KHF SCS that are effective at increasing bladder capacity (suppressing NDO) and increasing voiding efficiency (suppressing DSD) in healthy anesthetized rats before and after installation in the bladder of acetic acid, which generates reduced bladder capacity (NDO) and inefficient bladder emptying (DSD), as observed after SCI. Aim 2 is to determine the effects of KHF SCS on bladder capacity and voiding efficiency in anesthetized rats four weeks after complete spinal cord transection. These experiments will confirm that the parameters identified in Aim 1 remain effective following SCI. Aim 3 is to quantify the effects of KHF SCS on voiding behavior in awake behaving rats following contusion SCI. These experiments make use of a more translationally-relevant contusion model of SCI to determine the efficacy and tolerability of this proposed therapy. The proposed preclinical studies will establish the feasibility and appropriate stimulation parameters for this innovative approach to restore bladder function following SCI, and we anticipate pursuing subsequent translational studies in persons with SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1103 Clinical Sciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • RCDC

    Urologic Diseases

  • HRCS HC

    Renal and Urogenital

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science