Stimulation mediated sensory enhancement of the urethral afferents


Principal Investigator: Zachary C Danziger
Abstract: DESCRIPTION (provided by applicant): Urinary retention is a disease of the urinary tract that prevents hundreds of thousands of people from properly emptying the contents of their bladder. Urinary retention can be caused by many things such as natural aging, acute trauma (especially during surgical procedures), diabetes, multiple sclerosis and others. Despite the range of causes, a feature common to most cases of urinary retention is a reduced neural sensitivity for detecting fluid flow in the urethra. This reduction in sensitivity, in turn, limits the effectivenes of reflexes that naturally control bladder voiding. We hypothesize that enhancing urethral sensitivity will mitigate many of the symptoms associated with retention by allowing the reflexes to once again function properly. The work in this proposal will demonstrate that it is possible to enhance urethral sensitivity. To accomplish this enhancement we will use a process called stochastic resonance, where we inject sub-threshold levels of electrical noise (amounts small enough that they cannot be detected by the sensory neurons) directly into the urethra. This will be done in a rat model of the urinary tract. Stochastic resonance has been successful in other biological sensory systems and we hypothesize that these undetectable perturbations will lower the activation threshold of the urethral sensory neurons, effectively increasing their sensitivity o flow. We will demonstrate our findings by recording from the pudendal nerve, which carries sensory information from the urethra to the spinal cord. We will compare the pudendal nerve's response to fluid flow in the urethra both with and without the stimulation at a range of flowrates We can conclude that sensitivity was enhanced if more neural activity is observed in the presence of the stimulation than without it, and if slower flowrates can be detected with the stimulation it will also serve as evidence of enhanced sensitivity. Finally, a mathematical model of stochastic resonance in the lower urinary tract will be developed in tandem with the animal experiments. This model will allow us to simulate many different types of stimulation and flowrates to better guide the animal work. Using the model we can investigate a wide range of experiment parameters, many more than we could test using the biological system. We will use the model estimates of the optimal stimulation parameters and flowrates to give ourselves the best chance of success for enhancing urethral sensitivity.
Funding Period: 2013-09-01 - 2015-08-31
more information: NIH RePORT

Detail Information

Research Grants30

  1. PAHs: New Technologies and Emerging Health Risks
    David E Williams; Fiscal Year: 2013
    ..Accomplishing these goals will provide significant scientific advancement and improve the quality of life for impacted communities. ..
    Ramnik J Xavier; Fiscal Year: 2013
    ..These goals are fostered by Pilot/Feasibility Study awards which support new research initiatives as well as an enrichment program of seminars, workshops and symposia. ..
  3. A Murine Sox10 Dominant Negative COIN Allele for Functional Gene Analysis
    E Michelle Southard-Smith; Fiscal Year: 2013
  4. Pathophysiology of Alveolar Epithelial Lung Injury
    Jacob I Sznajder; Fiscal Year: 2013
    ..The insights gained from the data generated from these studies will provide novel molecular targets for the development of new therapeutic strategies to treat patients with lung injury. ..
  5. Sox10 Alleles for Functional Analysis of Glial Lineages
    E Michelle Southard-Smith; Fiscal Year: 2013
  6. Neural Prosthetic Control of Continence and Micturition
    Warren M Grill; Fiscal Year: 2013
    ..Successful completion of this project will advance the development of an effective neural prosthetic system for restoration of bladder function. ..
  7. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
    ..abstract_text> ..
  8. IBD and Mucosal Inflammation, Immunology, and Microbiology of the GI Tract
    Eugene B Chang; Fiscal Year: 2013
    ..Through its cost-effective, enabling technologies and services, the DDRCC has been a major factor in the advancement of scholarship and discovery in IBD and digestive diseases at the University of Chicago. ..
  9. Role of T cells in gastrointestinal manifestations of food allergy
    MARIA CECILIA BERIN; Fiscal Year: 2013
    ..This research focuses on a shared feature of all food allergic disorders, the food allergen-specific Th2 lymphocyte, and therefore we anticipate that this research will be relevant to a broad spectrum of food allergic disorders. ..
  10. Recovery of bladder reflexes and nerve regeneration after spinal cord injury
    Yu Shang Lee; Fiscal Year: 2013
    ..This multipartite strategy has the potential to lead to an unprecedented amount of functional plasticity/regeneration and bladder recovery after SCI. ..
    ..The research projects are supported by four Cores: a Mouse Model Core, a Histopathology Core, an Imaging and Cell Sorting Core and an Administrative Core. ..
  12. Severe Enteric Disease: Pathogenesis and Response
    James B Kaper; Fiscal Year: 2013
  13. Enteric Neuronal Development as a Determinant of Intestinal Inflammation
    Kara Gross Margolis; Fiscal Year: 2013
    ..Knowledge of interactions between the ENS and inflammatory effectors, therefore, has the potential to transform understanding and, ultimately, treatment of many intestinal disorders. ..
  14. Synaptic Function: Effects of the Nerve Injury, Repair, and Altered Activity
    Timothy C Cope; Fiscal Year: 2013
    ..The Resume and Summary of Discussion above summarizes the final outcome of the group discussion. OVERALL PROGRAM EVALUATION ..
  15. Mechanisms/Treatments of Lower Urinary Tract Dysfunction After Spinal Cord Injury
    ANTHONY JOHN KANAI; Fiscal Year: 2013
    ..We are confident that our experience and unique approaches will lead to a very interactive and fruitful program. ..