Neuropeptidergic Inhibition of Spinal Pain Transmission

描述(由申请人提供)：独立科学家奖(K02)的候选人寻求五年的工资支持，以提供释放时间来研究神经肽在介导炎性和神经病理性疼痛中的作用。他的综合方法包括药理学、行为学和分子研究。这位候选人在加州大学圣迭戈分校获得了博士学位，在加州大学旧金山分校与艾伦·巴斯鲍姆共事，现在是杜兰大学的药理学副教授。他发表了28篇原创文章(25篇作为第一/最后作者)和7篇特邀评论，并获得了研究疼痛和止痛的NRSA、FIRST(R29)、R21和R01奖项。他广泛的职业目标包括：1.将他目前的R01扩展为一个构思良好的长期研究计划，产生一种治疗慢性疼痛的新药物疗法(例如NPY受体激动剂)；2.继续与导师互动，这将促进他对慢性疼痛的生理、细胞和生化机制以及神经肽对其抑制的更深层次的理解；以及3.在分子生物学、病毒转染和条件转基因小鼠技术的利用方面继续合作和培训，以开发精确和有针对性的方法来解决慢性疼痛研究中的重要问题。杜兰大学仍然拥有丰富的智力成长和独立的教育机会，并为泰勒博士提供卓越的资源，包括实验室空间、设备、隔膜行为套件和内部研究资金。杜兰认为泰勒博士是该校坚定致力于研究的不可或缺的一部分，并于2004年提前授予他终身教职。根据K02基金的情况，该机构保证泰勒博士85%的时间将用于研究和职业发展活动。研究计划侧重于这样一个总体假设，即炎症或感觉神经损伤会减少背角NPY信号的突触前和突触后元素，从而促进伤害性神经传递，最终增加痛觉过敏和痛觉过敏。目的1利用新型受体亚型选择性拮抗剂和缺失突变小鼠，确定Y1或Y2受体对NPY作用的贡献。目的#2将损伤诱导的行为改变与NPY释放和Y1受体表达联系起来。目的#3利用微透析和免疫组织化学方法研究神经肽Y是否抑制P物质释放和背角伤害性反应神经元。

DESCRIPTION (provided by applicant): The candidate for an Independent Scientist Award (K02) seeks five years of salary support to provide release time to study the role of neuropeptides in mediating inflammatory and neuropathic pain. His integrative approach includes pharmacologic, behavioral and molecular studies. The candidate obtained a Ph.D. at UCSD, worked with Allan Basbaum at UCSF, and is now an Associate Professor of Pharmacology at Tulane University. He has published 28 original articles (25 as first/last author) plus 7 invited reviews and received NRSA, FIRST (R29), R21 and R01 grants to study pain and analgesia. His broad career goals include: 1. Extension of his current R01 into a well-conceived, long-term research program that yields a new pharmacotherapy for chronic pain (e.g. an NPY receptor agonist); 2. Continued interactions with mentors that will foster his deeper understanding of the physiological, cellular and biochemical mechanisms of chronic pain and its inhibition by neuropeptides; and 3. Continued collaborations and training in the utilization of molecular biological, viral transfection, and conditional transgenic mouse technologies so as to develop precise and targeted approaches to important questions in chronic pain research. Tulane remains rich in educational opportunities for intellectual growth and independence, and provides outstanding resources to Dr. Taylor including laboratory space, equipment, behavioral suites in the vivarium, and internal research funding. Tulane considers Dr. Taylor to be an integral part of its strong commitment to research, and granted him early tenure in 2004. Contingent upon K02 funding, the institution provides assurances that 85% of Dr.Taylor's time will be set aside for research and career development activities. The Research Plan focuses on the overall hypothesis that inflammatory or sensory nerve injury decreases presynaptic and postsynaptic elements of NPY signaling at the dorsal horn, thereby facilitating pronociceptive neurotransmission, and ultimately increasing allodynia and hyperalgesia. Aim #1 will determine the contribution of Y1 or Y2 receptors to the actions of NPY using new receptor subtype- selective antagonists, and deletion mutant mice. Aim #2 will correlate injury-induced changes in behavior with NPY release and Y1 receptor expression. Aim #3 will use microdialysis and immunohistochemistry to determine whether NPY inhibits substance P release and dorsal horn nociresponsive neurons.