Brain Stem Mechanisms of Opioid Induced Pain

阿片类药物引起疼痛的脑干机制

• 批准号: 7385881
• 负责人: TODD W VANDERAH
• 金额: $ 9.83万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7385881
• 关键词: Abate; Accounting; Acute; Address; Agonist; Animals; Appointment; Area; Arizona; Basic Science; Behavioral; Bilateral; Bolus Infusion; Brain; Brain Stem; Brain region; CTOP; Calcium; Cholecystokinin; Collaborations; Communities; Data; Development; Dialysis procedure; Dose; Drug Delivery Systems; Educational process of instructing; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Environment; Equipment; Exposure to; Fostering; Goals; Grant; Hunger; Infusion procedures; Interdisciplinary Study; International; Journals; K-Series Research Career Programs; Laboratories; Laboratory Research; Lesion; Measures; Mechanics; Mediating; Microdialysis; Microinjections; Monitor; Morphine; Naloxone; Narcotic Antagonists; Nature; Neuraxis; Neurobiology; Neurons; Opioid; Opioid Receptor; Pain; Pathway interactions; Peer Review; Pharmacology; Physical Dialysis; Physiological; Placebos; Postdoctoral Fellow; Potassium; Prevention; Principal Investigator; Publications; Publishing; Radioimmunoassay; Rattus; Reaction Time; Recruitment Activity; Regulation; Research; Research Activity; Research Infrastructure; Resource Sharing; Role; Science; Scientist; Sensory; Sensory Thresholds; Spinal; Spinal Cord; Stimulus; Students; Sufentanil; Tail; Taste Perception; Testing; Time; Universities; Withdrawal; awake; base; career; day; deltorphin; design; dorsal horn; driving force; endogenous opioids; expectation; extracellular; forging; immunoreactivity; implantation; in vivo; insight; interdisciplinary collaboration; interest; naltrindole; norbinaltorphimine; novel; osmotic minipump; prevent; programs; receptor; research study; response

DESCRIPTION (provided by applicant): My interest in research began as an undergraduate at the University of Arizona (U of A). Since that time I have developed as an independent scientist in the field of pain. Several milestones are noteworthy including the establishment of my laboratory, recruitment of students and a postdoctoral fellow, receiving my first 5 year R01 NIH-NIDA sponsored grant, invitations to speak at national/international meetings and in academic settings, forging new collaborations and continuous publications in peer reviewed journals. These accomplishments have offered a taste of a career in which I hunger for, however my appointment in the Department of Pharmacology came with a significant teaching commitment that, although important tends to abate my time for basic research. If I were to receive this Career Development Award, I would pursue specific research objectives including; 1) Continue to strengthen my primary research program; 2) Develop a new/extended hypothesis for a renewal of the current NIH-R01; 3) Publish; 4) Present my data at national/ international meetings; 5) Collaborate with the group of pain-neuroscientist/ pharmacologists/chemists here at the U of A. My research career goal is to establish an interdisciplinary research program aimed at understanding the mechanisms that drive the activation of supraspinal descending pain facilitatory pathways in the presence of sustained opioids. The ultimate goal of these studies is to understand the neurobiological consequences of sustained opioid administration and to determine the role of these adaptations. This proposal hypothesizes that morphine enhances cholecystokinin (CCK) release in the RVM which then promotes opioid-induced pain and antinociceptive "tolerance". The studies offer new insight into physiological mechanisms of opioid tolerance and strategies which might be employed to prevent opioid-induced pain and antinociceptive tolerance which may allow for the development of novel pain relieving compounds. The U of A has earned recognition as a top Research One University ranked 13th among public universities. The U of A has in place the infrastructure needed to support and oversee research activities including several core research laboratories, interdisciplinary academic programs and large multi-disciplinary center programs. These facilities were put into place to support and promote interdisciplinary collaborations which initiate new research and educational programs of high priority to the scientific community. I have adequate space, equipment, the ability to recruit graduate students from multiple programs, and have access to numerous shared resources. In summary, the U of A and the Department of Pharmacology provide an outstanding environment to promote science and foster career development.

描述（由申请人提供）： 我对研究的兴趣始于亚利桑那大学（A）的本科生。从那时起，我就成为痛苦领域的独立科学家。值得注意的值得注意的，包括建立我的实验室，招募学生和博士后研究员，我收到了我的前5年R01 NIH-NIHIDA赞助了Grant的Grant，在国家/国际会议和学术环境中发表演讲的邀请，在同行评审期刊上进行新的合作和连续出版物。这些成就提供了我渴望的职业，但是我在药理学系的任命具有重大的教学承诺，尽管重要的是减少了我进行基础研究的时间。如果我要获得这个职业发展奖，我将追求特定的研究目标，包括： 1）继续加强我的主要研究计划； 2）为当前NIH-R01的续订开发一个新的/扩展的假设； 3）发布； 4）在国家/国际会议上介绍我的数据； 5）与A的U型疼痛神经科学家/药物师/化学家一起合作。这些研究的最终目标是了解持续的阿片类药物给药的神经生物学后果，并确定这些适应的作用。该提议假设吗啡增强了RVM中的胆囊动蛋白（CCK）释放，然后促进阿片类药物诱导的疼痛和抗伤害感受性的“耐受性”。这些研究提供了对阿片类药物耐受性和策略的生理机制的新见解，这些机制可用于防止阿片类药物诱导的疼痛和抗伤害感受耐受性，这可能允许发展新型疼痛缓解化合物。 A的U赢得了公立大学中最高研究的认可。 A的U具有支持和监督研究活动所需的基础设施，包括几个核心研究实验室，跨学科的学术计划和大型多学科中心计划。建立了这些设施，以支持和促进跨学科的合作，这些合作启动了对科学界高度优先的新研究和教育计划。我有足够的空间，设备，能够从多个课程中招募研究生，并且可以访问众多共享资源。总而言之，A的U和药理学系为促进科学和培养职业发展提供了一个杰出的环境。