Capsaicin-sensitive primary afferent fibers and neuropathic pain

描述（由申请人提供）：Jennifer L. Gibbs, d.d.s.，博士在2008年7月完成她的牙髓实习期后被任命为助理兼职教授。她之前接受过系统神经科学研究方面的培训，包括生化分析、细胞培养、解剖研究和行为实验。这K-23指导病人导向的研究事业发展奖将用于启动她的职业生涯在翻译口面部疼痛的研究，重点是了解神经性疼痛（NP）的机制。研究计划：Gibbs博士提出了一系列研究来评估辣椒素敏感的初级传入神经元在介导NP中的作用，通过对被诊断为带状疱疹后神经痛（PHN）的受试者进行横断面研究，并使用口腔面部NP模型对动物进行一系列补充研究。在这些研究中，我们将确定辣椒素反应试验（CRT）与疼痛和感觉测量结果之间的关系，这些结果与高反应性原发性传入事件一致，以确定CRT是否有助于基于机制的NP诊断。此外，我们将测试对辣椒素有反应的PHN受试者具有不同的表皮和真皮神经支配模式的理论，并确定皮肤活检的组织学评估是否可以识别基于机制的NP分类的生物标志物。最后，将使用动物模型来研究辣椒素敏感初级传入神经末梢和中枢末梢在神经损伤情况下的作用。吉布斯将继续她之前与艾伦·巴斯鲍姆博士在他的实验室开始的工作，研究疼痛的基本机制和相关技术，包括神经解剖学和疼痛行为。此外，Gibbs博士将与UCSF疼痛临床研究中心的Rowbotham博士合作，进行感官测试研究并收集PHN受试者的活检。吉布斯博士将继续与施密特博士合作，确定NP的生物标志物，并在动物中开发一种新的口腔面部疼痛模型。她目前还在攻读临床研究硕士学位，以促进她进行转化研究的能力。吉布斯博士得到了内政部的全力支持，并将于2009年7月转为终身职位。

DESCRIPTION (provided by applicant): Jennifer L. Gibbs, D.D.S., Ph.D. was appointed as an Assistant Adjunct Professor after completing her Endodontic Residency in July 2008. She has prior training in systems neuroscience research including biochemical assays, cell culture, anatomical studies, and behavioral experiments. This K-23 Mentored Patient-Oriented Research Career Development Award will be used to launch her career in translational orofacial pain research with a focus on understanding the mechanisms of neuropathic pain (NP). Research Plan: Dr. Gibbs has propsed a series of studies to evaluate the role of capsaicin-sensitive primary afferent neurons in mediating NP by performing a cross-sectional study on subjects diagnosed with postherpetic neuralgia (PHN) and a complementary series of studies in animals using a model of orofacial NP. In these studies we will determine the relationship between a capsaicin response test (CRT) and outcomes of pain and sensory measures consistent with hyper-responsive primary afferents to determine if the CRT faciliatates a mechanism-based diagnosis of NP. In addition we will test the hjqjothesis that PHN subjects who respond to capsaicin have distinct epidermal and dermal innervation patterns and determine whether histological evaluation of skin biopsies can identify a biomarker for mechanism-based classification of NP. Finally, an animal model will be used to study the contribution of peripheral versus central terminals of capsaicin sensitive primary afferents in the setting of nerve injury Development Plan:Dr. Gibbs will continue her previously initiated work with Dr. Allan Basbaum in his laboratory studying basic mechanisms of pain and relevant techniques including neuroanatomy and pain behavior. In addition Dr. Gibbs will work with Dr. Rowbotham at the UCSF Pain Clinical Research Center to conduct sensory testing studies and collect biopsies from PHN subjects. Dr. Gibbs will continue collaborative efforts with Dr. Schmidt to identify biomarkers for NP and develop a new model of orofacial pain in animals. Dr. Gibbs is also currently pursuing a Master's in Clinical Research to facilitate her ability to perform translational research. Dr. Gibbs has the full support ofher home department and will transition to a tenure track position in July 2009. PUBLIC HEALTH RELEVANCE: These studies will yield novel and important insights into the mechanisms contributing th NP and help define populations (e.g. capsaicin responders) who are more likely to benefit from mechanims targeting analgesic therapies. Neuropathic pain has devastating impact on patients ability to inderact socially, work, and overall enjoyment of life. Improvement in diagnosis of NP is critical for better management of these patients.