CAREER DEVELOPMENT PROGRAM IN FUNCTIONAL NEUROIMAGING

吗啡仍然是控制剧烈疼痛的主要疗法。 不幸的是，一些最初有良好止痛效果的患者失去了疼痛。 控制，尽管提高了药物的剂量和效力。发展中的 耐受性、神经病理性疼痛和/或上升性伤害性刺激 疾病的强度是可能的解释。渲染解药是 目标，但往往没有补救措施可用。在某种程度上，容忍 减少疼痛控制，减少耐受性将改善患者 关心。研究的最终目的是扩大我们的理解和 改善对无法控制的疼痛综合征的管理。的主要目标 这一科学家发展奖是：i)在被提名者中发展特别 使用正电子发射断层扫描(PET)的技能和知识 阿片类药物的神经药理学；2)发展临床相关性 正电子发射计算机断层扫描技术用于评估神经生理对疼痛和 心理治疗。在培训计划中学到的技能将应用于 测试疼痛和鸦片类药物改变假说的方案 可用PET和右美沙芬测量的神经激活反应， 一种NMDA受体拮抗剂，可减弱对阿片类药物的耐受性。 将招募70名长期使用吗啡的幼稚患者。每个人 患者将被分配到接受吗啡的两个治疗组中的一个 使用右美沙芬或安慰剂治疗。病人将会入院 到医院(GCRC)24小时开始治疗并进行最佳滴定 并建立他们每天的吗啡给药方案。出院后， 计划缓释吗啡和P.R.N.实施即刻释放 吗啡将与测试药物/安慰剂一起开出。日记， 将使用电信和临床随访来监测日常疼痛 强度、副作用和吗啡的使用。七十个病人中的三十个 将在临床试验之前和之后进行疼痛激活研究 建立他们的神经激活模式(H2-15-O团注技术) 而且不需要椎管内注射芬太尼。这些结果将被比较 对18名正常人进行的神经激活性疼痛研究 在椎管内注射芬太尼之后。这些研究活动是最完美的 对被提名者的教育计划和职业目标进行补充。这个 研究与患者护理相关且有意义，并提供了一个场所 对于被提名人来说，实践从 教程和课程作业。这些综合活动将使 开发一位独立的临床科学家使用正电子发射计算机断层扫描来探索 疼痛问题和现有止痛药的局限性 药物。

Morphine continues to be the mainstay therapy for managing intense pain. Unfortunately, some patients who initially have good pain relief lose pain control despite advancing the dose and potency of medications. Evolving tolerance, neuropathic pain and/or ascending nociceptive stimulus intensity from disease are possible explanations. Rendering a cure is the goal, but often no remedy is available. To the extent that tolerance diminished pain control, curtailment of tolerance will improve patient care. The ultimate goal of the research is to expand our understanding and improve management of uncontrollable pain syndromes. The major goals of this Scientist Development Award are: I) to develop in the nominee special skills and knowledge in the use of Positron Emission Tomography (PET) and the neuropharmacology of opioids; and 2) develop clinically relevant techniques in PET to assess neurophysiologic responses to pain and therapy. The skills acquired in the training program will be applied to protocols which test the hypotheses that pain and opiates alter neuroactivation responses measurable with PET and that dextromethorphan, an NMDA receptor antagonist, attenuates tolerance to opiates. Seventy patients naive to chronic morphine use will be recruited. Each patient will be assigned to one of two treatment groups receiving morphine with either dextromethorphan or placebo therapy. Patients will be admitted to the hospital (GCRC) for 24 hours to begin therapy and optimally titrate and establish their daily morphine dosing regimen. Upon discharge, scheduled slow release morphine and P.R.N. administered immediate release morphine will be prescribe along with the test drug/placebo. Diaries, telecommunications and clinic follow-up will be used to monitor daily pain ihtensity, side-effects and morphine use. Thirty of the seventy patients will undergo a pain activation study before and after the clinical trial to establish their neuroactivation pattern (H2-15-O bolus technique) with and without intraspinal fentanyl injection. These results will be compared to neuroactivation pain studies performed in eighteen normals before and after intraspinal fentanyl. These research activities are the perfect complement to the nominees educational plan and career objectives. The research is relevant and meaningful to patient care and provides a venue for the nominee to practice the concepts and principles gained from the tutorials and coursework. These integrated activities will allow for the development of an independent clinical scientist using PET to explore the problems of pain and the limitations of currently available analgesic medications.