Epidermal Innervation as an Outcome Measure

表皮神经支配作为结果衡量标准

• 批准号: 7066669
• 负责人: DAVID N HERRMANN
• 金额: $ 16.61万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-15 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7066669
• 关键词: AIDS /HIV neuropathy; HIV infections; biopsy; clinical research; clinical trials; counseling; human subject; human therapy evaluation; immunocytochemistry; light microscopy; longitudinal human study; morphology; nervous system disorder diagnosis; neural conduction; neurobiology; outcomes research; pain; patient oriented research; polyneuritis; sensory neuropathy; sign /symptom; sodium channel; stimulus /response

DESCRIPTION (provided by applicant) This application describes a plan that combines recently developed clinical tests and laboratory methodologies to improve our ability to carry out therapeutic trials in small-fiber sensory neuropathies. This career development application will build upon the clinical expertise of Dr. Herrmann in neuromuscular disorders, electrophysiology, and peripheral nerve histopathology. The long-range goal of Dr. Herrmann is to develop a successful independent research program that includes both investigations of the pathomechanism of different small fiber sensory neuropathies and the performance of therapeutic trials in these disorders. To achieve these objectives the candidate will: 1) learn clinical research methodology through didactic course work, 2) study peripheral nerve biology and the neurobiology of pain through a structured reading program, 3) undertake a mentored, patient oriented research project aimed at the development of optimal outcomes measures for clinical trials in peripheral neuropathy, 4) develop collaborative research studies aimed at understanding the neurobiology of pain in small fiber neuropathies. The mentored research project will test the hypotheses that: 1)serial measurements of epidermal nerve fiber density (ENF) and morphology are useful as outcome measures in studies of small fiber sensory neuropathy; 2) redistribution and accumulation of novel PN3 sodium channels at sensory nerve terminals occur during the transition from asymptomatic to symptomatic HIV associated distal symmetrical polyneuropathy (DSP), and that these changes contribute to the production of neuropathic pain. This research project will be carried out in a large NIH-funded cohort at high risk for HIV-associated DSP. Through the use of serial punch skin biopsies, Dr. Herrmann will compare changes in ENF density and morphology and the level of expression of novel PN3 sodium channels at sensory nerve terminals to several clinical/laboratory measures which include: a) a patient generated pain scale; b) quantitative sensory testing; c) sural nerve conduction; and d) autonomic function. Dr. Herrmann will also examine a method to simplify the analysis of skin biopsy specimens, for easier application in large clinical trials.

描述（由申请人提供） 该应用程序描述了一个结合了最近开发临床的计划 测试和实验室方法论，以提高我们执行的能力 小纤维感觉神经病的治疗试验。这个职业发展 申请将基于Herrmann博士的临床专业知识 神经肌肉疾病，电生理学和周围神经 组织病理学。赫尔曼博士的远程目标是发展成功 独立研究计划，包括对 不同小纤维感觉神经病的病理机制和 这些疾病中治疗试验的表现。 为了实现这些目标，候选人将：1）学习临床研究 通过教学课程工作的方法，2）研究周围神经生物学和 通过结构化阅读计划的疼痛神经生物学，3）进行 旨在开发最佳的指导，以患者为导向的研究项目 周围神经病的临床试验的结果措施，4） 旨在理解疼痛神经生物学的协作研究 在小纤维神经病中。 指导研究项目将检验以下假设：1）串行 表皮神经纤维密度（ENF）和形态的测量很有用 作为小纤维感觉神经病研究的结果度量； 2） 新型PN3钠通道在感觉神经上的重新分布和积累 终端发生在从无症状到有症状的HIV过渡期间发生 相关的远端对称多发性病变（DSP），这些变化 有助于神经性疼痛的产生。 该研究项目将在High的大型NIH资助队列中进行 与HIV相关的DSP的风险。通过使用连续的打孔皮肤活检，博士 Herrmann将比较ENF密度和形态的变化以及 在感觉神经末端的新型PN3钠通道的表达 临床/实验室措施包括：a）患者产生疼痛量表； b）定量感觉测试； c）伴随神经传导； d）自主教 功能。 Herrmann博士还将研究一种简化分析的方法 皮肤活检标本，以便于在大型临床试验中使用。