Epidermal Innervation as an Outcome Measure

描述（由申请人提供） 该应用程序描述了一个计划，结合最近开发的临床 测试和实验室方法，以提高我们的能力， 小纤维感觉神经病的治疗试验。这种职业发展 申请将建立在Herrmann博士的临床专业知识基础上， 神经肌肉疾病、电生理学和外周神经 组织病理学赫尔曼博士的长期目标是开发一种成功的 独立的研究计划，包括调查的 不同小纤维感觉神经病变的病理机制及 这些疾病的治疗试验的性能。 为了实现这些目标，候选人将：1）学习临床研究 方法通过教学课程工作，2）研究周围神经生物学， 疼痛的神经生物学通过一个结构化的阅读程序，3）进行一个 指导，面向患者的研究项目，旨在开发最佳的 周围神经病变临床试验的结局指标，4）制定 旨在了解疼痛的神经生物学的合作研究 小纤维神经病变 指导研究项目将测试假设：1）连续 表皮神经纤维密度（ENF）和形态学的测量是有用的 作为小纤维感觉神经病研究的结局指标; 2） 新的PN 3钠通道在感觉神经上的重新分布和积聚 在从无症状到有症状的HIV转变过程中， 相关的远端对称性多发性神经病（DSP），这些变化 导致神经性疼痛。 这项研究项目将在一个大型NIH资助的队列中进行， 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 新的PN 3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）定量感觉测试; c）腓肠神经传导;和d）自主神经 功能赫尔曼博士还将研究一种方法，以简化分析， 皮肤活检标本，便于在大型临床试验中应用。

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.