Integrative Medicine for Pain Management in Sickle Cell Disease

项目摘要/摘要 镰状细胞病(SCD)以慢性疼痛为特征，伴有潜在的氧化应激，炎症， 低氧和中枢敏化。阿片类药物是SCD疼痛治疗的主要药物，但往往无效 并伴随着显著的副作用。使用非药物治疗的潜在好处(例如 针灸、催眠、太极、瑜伽)已有报道，但由于缺乏系统性应用 令人信服的证据。在人源化的SCD转基因小鼠模型中，电针(EA) 在不使用麻醉或约束的情况下给药。我们观察了产生的止痛的个体差异。 电针后疼痛减轻程度与外周/中枢的表达呈正相关。 炎症介质。需要探索不同止痛的潜在机制，以便 制定有效的策略，以加强对电针反应不佳的疼痛缓解不足。具体的 该项目的目的是1)确定特定的炎症生物标志物(例如物质)的水平 P、肿瘤坏死因子-α、白介素1β、白介素6)参与电针对镰状小鼠不同的镇痛作用。 以炎性生物标志物为靶点的痛敏机制阻碍电针的镇痛作用 较差的响应者，以及3)确定选定的循环生物标志物水平与 镰刀患者的针刺镇痛程度及其与静息状态变化的关系 功能磁共振成像和特异性脑神经代谢产物配合针刺的干预。的主要目标是 该奖项的导师(K99)部分是为候选人提供神经成像疼痛的全面培训 她获得终身教职所需的研究和临床技能跟踪教师职位并成功领导她 拥有独立的研究项目。K99候选人提出的大部分研究和培训 这一阶段将在明尼苏达大学完成，由格雷戈里的卡尔普纳·古普塔博士指导 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容外在的 密歇根大学理查德·哈里斯博士的指导将指导候选人进行与核磁共振相关的培训 技巧。加州大学洛杉矶分校(UCLA)的朗尼·泽尔策(Lonnie Zeltzer)博士是综合医学领域的领先内科科学家，也将担任 与共同导师就拟议研究的临床相关方面向候选人提供建议 维塞洛蒂医生。这些导师和顾问都是世界知名的分子/生理学专家 分别与SCD/癌症或疼痛神经成像相关的疼痛研究。明尼苏达大学 非常适合项目的K99阶段，因为有可用的资源，包括致力于 到基础和转化性疼痛研究和指导，致力于研究的磁共振成像(MRI) 扫描仪和最先进的疼痛测试设备，以及充足的实验室和办公空间 医学和放射学。在完成奖励的K99部分后，候选人将非常适合 过渡到终身教职。

Project Summary/Abstract Sickle cell disease (SCD) is characterized by chronic pain with underlying oxidative stress, inflammation, hypoxia and central sensitization. Opioids are the mainstay of pain therapy for SCD, but are often ineffective and associated with significant side effects. Potential benefits of using nonpharmacological therapy (e.g. acupuncture, hypnosis, Tai chi, Yoga) have been reported, but not been systematically applied due to lack of compelling evidence. In a humanized transgenic mouse model of SCD, electroacupuncture (EA) was administered without using anesthesia or restraints. We observed individual differences in analgesia produced by EA, and the intensity of pain reduction positively correlated with the expression of peripheral/central inflammatory mediators. The underlying mechanisms of varying analgesia need to be explored in order to develop an effective strategy to potentiate the insufficient pain relief of the poor responders to EA. The specific aims of this project are to 1) determine whether the levels of specific inflammatory biomarkers (e.g. substance P, TNF-α, IL-1β, IL-6) contribute to the varied analgesic effect of EA in sickle mice, 2) demonstrate the mechanisms underlying hyperalgesia that target inflammatory biomarkers hamper the analgesic effect of EA in poor responders, and 3) determine the correlations between the levels of selected circulating biomarkers and the degree of acupuncture analgesia in sickle patients, and how they correlate with the changes of resting state fMRI and specific brain neurometabolites with the intervention of acupuncture. The primary goal of the mentored (K99) portion of the award is to give the candidate the comprehensive training in neuroimaging pain research and clinical skills necessary for her to obtain a tenure track faculty position and successfully lead her own independent research program. The majority of studies and training proposed by the candidate for K99 phase will be completed at the University of Minnesota, under the mentorship of Drs. Kalpna Gupta, Gregory Vercellotti, and Donald Simone, with the collaboration of Drs. Xiao-hong Zhu and Al Beitz. The external mentorship of Dr. Richard Harris from University of Michigan will guide the candidate in training related to MRI techniques. Dr. Lonnie Zeltzer (UCLA), a leading physician scientist in integrative medicine, will also serve as a co-mentor in advising the candidate on the clinically relevant aspects of the proposed studies with co-mentor Dr. Vercellotti. These mentors and consultants are world-renowned experts in either molecular/physiological pain research associated with SCD/cancer, or, pain neuroimaging, respectively. The University of Minnesota is ideal for the K99 phase of the project because of the available resources, including faculty who are committed to basic and translational pain research and mentoring, research-devoted magnetic resonance imaging (MRI) scanners and state-of-the-art pain testing equipment, and ample laboratory and office space in Departments of Medicine and Radiology. Upon completing the K99 portion of the award, the candidate will be well suited to make the transition to a tenure-track faculty position.