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）患者的主要问题。此外，泌尿系统功能缺陷是影响SCI患者生活质量最重要因素之一。脊髓损伤的一个常见并发症是神经源性膀胱的发展，这涉及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和括约肌-逼尿肌协同失调，导致协调性丧失26。在过去数年，脊髓损伤患者的主要死因是肾衰竭76。然而，泌尿外科管理的改进降低了这一领域的死亡率，但目前患者的泌尿外科治疗方案往往难以维持，患者依从性低33。目前的治疗方案的一些问题包括：反复感染和疤痕频繁导尿，性功能障碍的外科手术后的副作用，药物的不良反应，以及未能建立推荐的指南和膀胱管理协议。在慢性SCI中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道，包括便秘，粪便嵌塞和失禁，以及腹胀引起的疼痛增加66; 68; 60。患者 能够通过手指肛门直肠刺激以启动反射性收缩排便， 通过数字疏散68.膀胱功能障碍和结直肠问题是SCI人群中显著发病率和死亡率的原因29; 67。因此，为了改善和更好地帮助膀胱和肠功能障碍患者，需要更好地了解慢性损伤后的解剖学和生理学。我们实验室的解剖追踪研究和初步电生理记录的证据表明，膀胱和结肠不仅受脊髓传入神经支配，而且也受迷走神经支配。在中枢通路受损的病理条件下，如SCI，迷走神经可能起到促进作用，实际上导致功能障碍。为了评估迷走神经受累的程度，本研究的目的是：1）使用雄性大鼠的神经解剖追踪技术，评估结状神经节中膀胱和结肠感觉传入的程度、与结肠的会聚程度以及这些神经元的组织化学表型; 2）使用体外和体内电生理记录，与正常对照相比，在组织刺激和/或慢性脊髓横断条件下，追踪的膀胱和结肠感觉传入神经的结状神经节神经元反应特性的可塑性相关变化。该项目旨在证明迷走神经传入直接从大鼠膀胱和结肠传递到尾侧髓质，并且可以基于其组织化学特征和对组织刺激和/或SCI的响应特性来表征。最终的目标是确定迷走神经作为一个潜在的来源，幻影的感觉，产生于一个“临床”（ASIA标准）以及一个“解剖学”的完整的SCI水平以下，希望提供一个 新的治疗靶点。

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.