Capsaicin-sensitive primary afferent fibers and neuropathic pain

描述(申请人提供)：詹妮弗·L·吉布斯博士，博士，2008年7月完成牙髓住院医师资格后被任命为助理教授。她曾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、解剖学研究和行为实验。这项K-23指导的以患者为导向的研究职业发展奖将用于启动她在翻译口面部疼痛研究方面的职业生涯，重点是了解神经病理性疼痛(NP)的机制。研究计划：Gibbs博士提出了一系列研究，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，以及使用口腔面部NP模型在动物身上进行的一系列补充研究，来评估辣椒素敏感的初级传入神经元在调节NP中的作用。在这些研究中，我们将确定辣椒素反应试验(CRT)与高反应性初级传入的疼痛和感觉测量结果之间的关系，以确定CRT是否有助于NP的基于机制的诊断。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假设，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分类的生物标记物。最后，一个动物模型将被用来研究辣椒素敏感初级传入的外周和中央终末在神经损伤发展计划设定中的作用：Gibbs博士将继续她之前与Allan Basbaum博士在他的实验室中开始的工作，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，吉布斯博士将在加州大学旧金山分校疼痛临床研究中心与罗伯坦博士合作，进行感官测试研究，并收集PHN受试者的活组织检查。吉布斯博士将继续与施密特博士合作，以确定NP的生物标记物，并开发一种新的动物口腔面部疼痛模型。吉布斯博士目前还在攻读临床研究硕士学位，以提高她进行转化性研究的能力。吉布斯博士得到了内政部的全力支持，将于2009年7月过渡到终身教职。 公共卫生相关性：这些研究将对导致THNP的机制产生新的和重要的见解，并有助于确定更有可能从针对止痛治疗的机制中受益的人群(例如辣椒素应答者)。神经性疼痛对患者的社交、工作和整体生活享受能力具有毁灭性的影响。提高NP的诊断水平是更好地处理这些患者的关键。

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.