Capsaicin-sensitive primary afferent fibers and neuropathic pain

辣椒素敏感的初级传入纤维和神经性疼痛

• 批准号: 7879429
• 负责人: JENNIFER LYNN GIBBS
• 金额: $ 5.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-02-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7879429
• 关键词: Acute; Affect; Afferent Neurons; Age; Analgesics; Anesthetics; Animal Model; Animals; Area; Behavior; Behavioral; Biochemical; Biological Assay; Biological Markers; Biopsy; Capsaicin; Cell Culture Techniques; Classification; Clinical Research; Cream; Cross-Sectional Studies; Data; Dermal; Detection; Development; Development Plans; Diagnosis; Disease Outbreaks; Doctor of Dental Surgery; Doctor of Philosophy; Endodontics; Evaluation; Fiber; Functional disorder; Herpes zoster disease; Herpesvirus Type 3; Home environment; Hyperalgesia; Image; Immunohistochemistry; Laboratory Study; Lidocaine; Life; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Modeling; Molecular; Neuroanatomy; Neurons; Neurosciences Research; Orofacial Pain; Outcome; Pain; Pain Research; Patients; Pattern; Peripheral; Peripheral nerve injury; Play; Population; Positioning Attribute; Postherpetic neuralgia; Principal Investigator; Quality of life; Rattus; Research; Research Personnel; Residencies; Role; Secondary to; Sensory; Series; Site; Skin; Symptoms; System; TRPV1 gene; Techniques; Testing; Tissues; Training; Translational Research; Trigeminal nerve structure; Work; allodynia; base; capsaicin receptor; career; central sensitization; clinically significant; cohort; experience; follow-up; inflammatory pain; insight; mechanical allodynia; nerve injury; nerve supply; neurochemistry; novel; orofacial; pain behavior; painful neuropathy; professor; public health relevance; relating to nervous system; research study; response; tool

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.

描述（由申请人提供）：Jennifer L.吉布斯，D.D.S.，博士2008年7月完成牙髓病学住院医师培训后，被任命为助理兼职教授。她曾接受过系统神经科学研究的培训，包括生化分析、细胞培养、解剖学研究和行为实验。这个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的职业生涯在翻译orofacial疼痛研究，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，通过对诊断为带状疱疹后神经痛（PHN）的受试者进行横断面研究，并使用口面NP模型在动物中进行一系列补充研究，以评估辣椒素敏感的初级传入神经元在介导NP中的作用。在这些研究中，我们将确定辣椒素反应试验（CRT）和与高反应初级传入一致的疼痛和感觉测量结果之间的关系，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hjqjothesis，并确定皮肤活检的组织学评价是否可以鉴定用于NP的基于机制的分类的生物标志物。最后，动物模型将用于研究辣椒素敏感的初级传入神经的外周与中枢末梢在神经损伤环境中的作用。发展计划：Gibbs博士将继续她先前与Allan Basbaum博士在他的实验室开展的工作，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，进行感觉测试研究，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，以确定NP的生物标志物，并开发一种新的动物口面疼痛模型。吉布斯博士目前还在攻读临床研究硕士学位，以提高她进行转化研究的能力。吉布斯博士得到了她的内政部的全力支持，并将于2009年7月过渡到终身职位。 公共卫生相关性：这些研究将产生新的和重要的见解的机制，有助于NP和帮助定义人群（如辣椒素反应者）谁更有可能受益于机制靶向镇痛治疗。神经性疼痛对患者的社交、工作和整体生活享受的能力具有破坏性影响。提高NP的诊断对于更好地管理这些患者至关重要。