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（U of A）的本科生。从那时起，我已经发展成为疼痛领域的独立科学家。几个里程碑是值得注意的，包括我的实验室的建立，学生和博士后研究员的招聘，收到我的第一个5年R 01 NIH-NIDA赞助的补助金，邀请在国家/国际会议和学术环境中发言，在同行评审的期刊上建立新的合作和持续的出版物。这些成就提供了一个我渴望的职业生涯的味道，但是我在药理学系的任命带来了一个重要的教学承诺，虽然重要，但往往会减少我的时间进行基础研究。如果我获得这个职业发展奖，我将追求具体的研究目标，包括：1）继续加强我的主要研究计划; 2）为更新当前的NIH-R 01开发一个新的/扩展的假设; 3）出版; 4）在国家/国际会议上展示我的数据; 5）与疼痛神经科学家/药理学家/化学家的小组合作。我的研究生涯目标是建立一个跨学科的研究计划，旨在了解在持续阿片类药物存在下，驱动脊髓上下行疼痛促进通路激活的机制。这些研究的最终目标是了解持续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。该建议假设吗啡增强RVM中胆囊收缩素（CCK）的释放，然后促进阿片类药物诱导的疼痛和抗伤害性“耐受”。这些研究为阿片类药物耐受的生理机制和可能用于预防阿片类药物诱导的疼痛和抗伤害耐受的策略提供了新的见解，这些策略可能会开发新的疼痛缓解化合物。A的U赢得了公认的顶级研究一所大学在公立大学中排名第13位。A的U已经到位所需的基础设施，以支持和监督研究活动，包括几个核心研究实验室，跨学科的学术课程和大型多学科中心计划。这些设施的建立是为了支持和促进跨学科的合作，从而启动科学界高度重视的新的研究和教育计划。我有足够的空间，设备，从多个项目招收研究生的能力，并有机会获得许多共享资源。总之，A的U和药理学系提供了一个优秀的环境，以促进科学和促进职业发展。