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的临床的计划 测试和实验室方法，以提高我们的执行能力 小纤维感觉神经病的治疗试验。这个职业发展 该应用程序将建立在赫尔曼博士的临床专业知识的基础上 神经肌肉疾病、电生理学和周围神经 组织病理学。 Herrmann 博士的长期目标是开发一种成功的 独立研究计划，包括对 不同小纤维感觉神经病的发病机制及 对这些疾病进行治疗试验。 为了实现这些目标，候选人将：1）学习临床研究 通过教学课程的方法论，2）研究周围神经生物学和 通过结构化阅读计划了解疼痛的神经生物学，3）进行 指导的、以患者为导向的研究项目，旨在开发最佳的 周围神经病临床试验的结果测量，4) 制定 旨在了解疼痛的神经生物学的合作研究 在小纤维神经病中。 指导研究项目将测试以下假设：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测量； 2） 感觉神经新型 PN3 钠通道的重新分布和积累 终末期发生在从无症状到有症状的艾滋病毒转变过程中 相关的远端对称性多发性神经病（DSP），并且这些变化 有助于神经性疼痛的产生。 该研究项目将在 NIH 资助的大型高水平队列中进行 HIV 相关 DSP 的风险。通过使用连续打孔皮肤活检，博士。 Herrmann 将比较 ENF 密度和形态的变化以及 新型 PN3 钠通道在感觉神经末梢的表达 临床/实验室测量，包括： a) 患者产生的疼痛量表； b) 定量感官检验； c) 腓肠神经传导； d) 自主的 功能。 Herrmann 博士还将研究一种简化分析的方法 皮肤活检标本，更容易应用于大型临床试验。