Effects of spinal cord injury on vagal afferents from the rat bladder and colon.

描述（由申请人提供）：继发性健康并发症是脊髓损伤（SCI）患者主要关注的问题。此外，泌尿功能障碍是影响脊髓损伤患者生活质量的重要因素之一。脊髓损伤的常见并发症是神经源性膀胱的发展，包括下尿路功能障碍和自主控制的丧失。并发症包括逼尿肌过度活动，导致尿失禁，膀胱组织壁内持续高压，括约肌-逼尿肌协同作用障碍，导致协调性丧失26。在过去几年中，脊髓损伤患者死亡的主要原因是肾功能衰竭。然而，泌尿系统管理的改善降低了该地区的死亡率，但目前的泌尿系统治疗方案往往难以维持，患者的依从性较低33。目前治疗方案的一些问题包括：反复感染和频繁导尿留下的疤痕，手术后的性功能障碍副作用，药物的不良反应，以及未能建立膀胱管理的推荐指南和方案。慢性脊髓损伤同样重要的是失去对排便的有意识控制。患者出现神经源性肠病，包括便秘、粪便嵌塞和尿失禁，以及腹胀引起的疼痛增加66；68年;60. 病人

DESCRIPTION (provided by applicant): 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.