Secondary health complications present a major concern for people living with spinal cord injury (SCI). Furthermore, deficits in urological functin rank high as one of the most important factors affecting quality of life for SCI patients 6. A common complication of SCI is the development of a neurogenic bladder, which involves lower urinary tract dysfunction and a loss of voluntary control. Complications include overactivity of th detrusor muscle, leading to urinary incontinence, sustained high pressure within the bladder tissue walls and sphincter-detrusor dyssynergia, resulting in a loss of coordination 26. In previous years, the leading cause of death in SCI patients was due to renal failure 76. However, improvements in urological management have reduced mortality rates in this area, but current urological treatment options for patients are often difficult to sustain and have low patient compliance 33. Some of the problems with current treatment options include: repeated infections and scarring from frequent catheterization, sexual dysfunction side effects following surgical procedures, adverse reactions to pharmaceuticals, and failure to establish recommended guidelines and protocols for bladder management. Equally important in chronic SCI is a loss of conscious control of defecation. Patients develop a neurogenic bowel that includes constipation, fecal impaction and incontinence, and increased pain from abdominal distention 66;68;60. Patients are able to defecate by either digital ano-rectal stimulation to initiate reflexive contractions or through digital evacuation 68. Both urinary bladder dysfunction and colorectal problems are causes of significant morbidity and mortality in the SCI population 29;67. Therefore, in order to improve and better assist patients with bladder and bowel dysfunction, a better understanding of the anatomy and physiology following chronic injury is needed. Evidence from anatomical tracing studies as well as preliminary electrophysiology recordings from our lab indicates that the bladder and colon are not only innervated by spinal afferents, but by the vagus nerve as well. In pathological conditions, such as SCI, where central pathways are compromised, the vagus nerve may take on a faciliatory role and actually contribute to dysfunction. In order to assess the degree of vagal involvement, the purpose of this study is 1) to evaluate, using neuroanatomical tracing techniques in male rats, the extent of urinary bladder and colon sensory afferents in nodose ganglia, the degree convergence with the colon, and the histochemical phenotype of such neurons and 2) to identify, using in vitro and in vivo electrophysiological recordings, plasticity-related changes in nodose ganglion neuronal response properties of traced urinary bladder and colon sensory afferents under conditions of tissue irritation and/or chronic spinal transection relative to normal controls. This project aims o demonstrate that vagal afferents are conveyed directly from the rat bladder and colon to the caudal medulla and can be characterized based upon their histochemical signature and response properties to tissue irritation and/or SCI. The ultimate goal is to identify the vagus nerve as a potential source of phantom sensations that arise from below the level of a "clinically" (ASIA criteria) as well as an "anatomically" complete SCI with the hope of providing a novel therapeutic target for SCI patients.

Public Health Relevance

The goal of this project is to study the role of the vagus nerve with respect to bladder and bowel function, with an emphasis on its contribution in a clinically relevant rodent spinal cord injury model. Determining the anatomical connections and physiological responses of the vagus with respect to the bladder and distal colon will aide in the development of novel therapeutic devices for urinary/bowel disorders, including dysfunction after chronic spinal cord injury.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F01-F (20))
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Ludwig, Kip A
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University of Louisville
Anatomy/Cell Biology
Schools of Medicine
United States
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Herrity, April N; Rau, Kristofer K; Petruska, Jeffrey C et al. (2014) Identification of bladder and colon afferents in the nodose ganglia of male rats. J Comp Neurol 522:3667-82