Epidermal Innervation as an Outcome Measure

描述(由申请人提供) 此应用程序描述了一个结合了最近开发的临床应用的计划 测试和实验室方法，以提高我们进行 小纤维感觉神经病的治疗试验。这份职业发展 应用程序将建立在Herrmann博士在 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临床意义 治疗试验在这些疾病中的表现。 为了实现这些目标，应聘者将：1)学习临床研究 方法通过授课工作，2)学习周围神经生物学和 通过有组织的阅读计划研究疼痛的神经生物学，3)进行 有指导、以患者为导向的研究项目旨在开发最优 周围神经病临床试验的结果衡量标准，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。 指导研究项目将检验以下假设：1)系列 测量表皮神经纤维密度和形态是有用的。 作为小纤维感觉神经病研究的结果指标； 新的PN3钠通道在感觉神经的重新分布和蓄积 在从无症状艾滋病毒向有症状艾滋病毒的过渡过程中发生终末期 相关的远端对称性多发性神经病(DSP)以及这些变化 导致神经病理性疼痛的产生。 这项研究项目将在美国国立卫生研究院资助的大型队列中进行。 HIV相关数字信号处理器的风险。通过使用连续冲压皮肤活检，Dr。 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/实验室措施，包括：a)患者产生的疼痛程度； B)定量感觉测试；c)腓肠神经传导；d)自主神经 功能。赫尔曼博士还将研究一种简化分析的方法 皮肤活检标本，便于在大型临床试验中使用。

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.