CAREER DEVELOPMENT PROGRAM IN FUNCTIONAL NEUROIMAGING

吗啡仍然是治疗剧烈疼痛的主要疗法。 不幸的是，有些病人最初有很好的疼痛缓解失去疼痛 尽管提高了药物的剂量和效力，演变 耐受性、神经性疼痛和/或上升性伤害性刺激 疾病强度是可能的解释。提供治疗是 目标，但往往没有补救措施。在某种程度上， 减少疼痛控制，减少耐受性将改善患者 在乎研究的最终目的是扩大我们的理解， 改善无法控制疼痛综合征的管理。的主要目标 这个科学家发展奖是：我）在提名特别发展 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）开发临床相关 PET技术评估对疼痛的神经生理反应， 疗法在培训计划中获得的技能将应用于 测试疼痛和阿片类药物改变 可以用PET和美沙芬测量神经激活反应， 一种NMDA受体拮抗剂，减弱对阿片类药物的耐受性。 将招募70名未接受过长期吗啡使用的患者。每个 患者将被分配到接受吗啡的两个治疗组之一 服用美沙芬或安慰剂病人将被接纳 到医院（GCRC）24小时，以便开始治疗并进行最佳滴定 并建立他们每天的吗啡剂量一旦出院， 定时缓释吗啡和P.R. N施用的立即释放 吗啡将与试验药物/安慰剂一起开沿着。日记， 电信和诊所随访将用于监测日常疼痛 强度副作用和吗啡的使用七十个病人中的三十个 将在临床试验前后进行疼痛激活研究 建立其神经激活模式（H2-15-O推注技术）， 椎管内不注射芬太尼。这些结果将被比较 在18名正常人中进行的神经激活疼痛研究， 在椎管内芬太尼之后。这些研究活动是完美的 补充被提名人的教育计划和职业目标。的 研究与患者护理相关且有意义， 为被提名人实践的概念和原则， tutorials教程and coursework课程.这些综合活动将使 开发一个独立的临床科学家使用PET来探索 疼痛的问题和目前可用的止痛剂的局限性 药物治疗

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.