Brain Stem Mechanisms of Opioid Induced Pain

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，我就成了疼痛领域的一名独立科学家。有几个里程碑值得注意，包括我的实验室的建立，招收学生和博士后研究员，收到我的第一个5年R01 NIH-NIDA资助的资助，邀请我在国家/国际会议和学术环境中发言，建立新的合作伙伴关系，并在同行评议的期刊上持续发表文章。这些成就让我尝到了我渴望的职业的滋味，然而，我在药理学系的任命伴随着重大的教学承诺，尽管这很重要，但往往会减少我从事基础研究的时间。如果我获得这个职业发展奖，我会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)为更新现有的NIH-R01制定一个新的/扩展的假说；3)发表文章；4)在国内/国际会议上展示我的数据；5)与亚利桑那大学的疼痛神经学家/药理学家/化学家小组合作。我的研究职业目标是建立一个跨学科的研究计划，旨在了解在持续的阿片类药物存在的情况下，驱动脊柱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阿片类药物持续给药的神经生物学后果，并确定这些适应的作用。这一假设假设吗啡促进了RVM中CCK的释放，进而促进了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提供了新的见解，并可能用于预防阿片类药物诱导的疼痛和抗伤害耐受，这可能有助于开发新的止痛化合物。阿肯色州大学被公认为一流的研究型大学，在公立大学中排名第13。亚利桑那州大学拥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、跨学科学术项目和大型多学科中心项目。建立这些设施是为了支持和促进跨学科合作，从而启动科学界高度重视的新的研究和教育方案。我有足够的空间、设备，有能力从多个专业招收研究生，并有权获得大量共享资源。总而言之，亚利桑那州大学和药理学系为促进科学和促进职业发展提供了一个良好的环境。

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.