Loss of bladder control as a result of neurological disease or injury such as spinal cord injury (SCI) has devastating effects. SCI results in loss of voluntary control of bladder evacuation, bladder hyper-reflexia, and bladder sphincter dysynergia. These factors often lead to ureteric reflux and obstruction, infection of the kidneys, long-term renal damage, episodes of autonomic dysreflexia with dangerous rises in blood pressure, incontinence which contributes to skin breakdown, as well as frequent urinary tract infections. Loss of bladder control also has profound social impact and leads to decreased quality of life, as well as large direct medical costs from procedures, supplies, and medication. The long-term goal of this research is to develop a neural prosthesis to restore bladder function (continence and micturition) in persons with neurological disorders, particularly spinal cord injury. Restoration of bladder evacuation and continence in individuals with SCI by electrical stimulation of the sacral nerve roots and surgical transection of sacral sensory nerve roots (dorsal rhizotomy) has resulted in documented medical, quality of life, and financial benefits. However, the widespread application of existing technology is limited by the objection of potential candidates to the irreversible dorsal rhizotomy and the complex surgical implant procedure. We propose an innovative approach to restoration of bladder function using a single multi-electrode nerve cuff implanted on the pudendal nerve to detect the onset of hyper-reflexive bladder contractions by electrical recording, to arrest nascent hyper-reflexive bladder contractions by electrical stimulation of pudendal genital afferent nerve fibers, and to produce on-demand bladder evacuation by electrical stimulation of pudendal urethral afferent nerve fibers. This innovative approach differs substantially from existing approaches using electrical stimulation of the spinal roots in that it does not require a spinal laminectomy, does not require irreversible surgical transection of the sacral sensory nerve roots, and stimulates the afferent rather than the efferent side of the system. This is expected to increase the population of individuals who can benefit from neural prosthetic technology, while maintaining the documented benefits. The objective of the proposed work is to demonstrate the feasibility of this approach using complementary experiments in an animal model and in persons with spinal cord injury. Successful completion of this project will lead to the development of an effective neural prosthetic system for restoration of bladder function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS050514-02
Application #
7005707
Study Section
Special Emphasis Panel (ZRG1-MOSS-G (01))
Program Officer
Pancrazio, Joseph J
Project Start
2005-01-01
Project End
2009-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
2
Fiscal Year
2006
Total Cost
$347,757
Indirect Cost
Name
Duke University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Danziger, Zachary C; Grill, Warren M (2017) Sensory feedback from the urethra evokes state-dependent lower urinary tract reflexes in rat. J Physiol 595:5687-5698
Gonzalez, Eric J; Grill, Warren M (2017) The effects of neuromodulation in a novel obese-prone rat model of detrusor underactivity. Am J Physiol Renal Physiol 313:F815-F825
McGee, Meredith J; Swan, Brandon D; Danziger, Zachary C et al. (2017) Multiple Reflex Pathways Contribute to Bladder Activation by Intraurethral Stimulation in Persons With Spinal Cord Injury. Urology 109:210-215
Danziger, Zachary C; Grill, Warren M (2016) Estimating postvoid residual volume without measuring residual bladder volume during serial cystometrograms. Am J Physiol Renal Physiol 311:F459-68
Medina, Leonel E; Grill, Warren M (2016) Nerve excitation using an amplitude-modulated signal with kilohertz-frequency carrier and non-zero offset. J Neuroeng Rehabil 13:63
McGee, Meredith J; Grill, Warren M (2016) Temporal pattern of stimulation modulates reflex bladder activation by pudendal nerve stimulation. Neurourol Urodyn 35:882-887
Langdale, Christopher L; Grill, Warren M (2016) Phasic activation of the external urethral sphincter increases voiding efficiency in the rat and the cat. Exp Neurol 285:173-181
Danziger, Zachary C; Grill, Warren M (2016) Sensory and circuit mechanisms mediating lower urinary tract reflexes. Auton Neurosci 200:21-28
McGee, Meredith J; Grill, Warren M (2016) Modeling the spinal pudendo-vesical reflex for bladder control by pudendal afferent stimulation. J Comput Neurosci 40:283-96
Grill, Warren M (2015) Model-based analysis and design of waveforms for efficient neural stimulation. Prog Brain Res 222:147-62

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