Integrative Medicine for Pain Management in Sickle Cell Disease

镰状细胞病疼痛管理的综合医学

基本信息

批准号：
10683217
负责人：
Ying Wang
金额：
$ 24.09万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-17 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10683217
关键词：
Absence of pain sensation Acupuncture Analgesia Acupuncture Therapy Acute Pain Adjuvant Adverse drug effect Analgesics Anesthesia procedures Attenuated Award Biological Markers Brain Brain Injuries Certification Chronic Clinical Clinical Skills Collaborations Complex Data Data Analyses Doctor of Philosophy Effectiveness Electroacupuncture Equipment Faculty Fright Functional Imaging Functional Magnetic Resonance Imaging Glutamates Goals Hospitalization Hyperalgesia Hypnosis Hypoxia Individual Individual Differences Inflammation Inflammation Mediators Inflammatory Integrative Medicine Intellectual Interest Interleukin-1 beta Interleukin-6 Intervention Labor Pain Laboratories Lead MAP Kinase Gene Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Malignant Neoplasms Mediating Mediator Medicine Mentors Mentorship Methods Michigan Minnesota Molecular Motivation Mus Neurogenic Inflammation Neuroglia Neuropeptides Nociception Nociceptors Nonpharmacologic Therapy Opioid Organ Oriental Medicine Outcome Oxidative Stress Pain Pain Measurement Pain Research Pain intensity Pain management Pathway interactions Patient imaging Patients Peripheral Peripheral Nerves Phase Phosphorylation Physicians Physiological Plasma Positioning Attribute Protons Qualifying Radiology Specialty Reactive Oxygen Species Recurrence Renal clearance function Reperfusion Injury Reporting Research Research Personnel Resources Rest Scientist Sickle Cell Anemia Skin Spinal Spinal Cord Substance P TNF gene Tai Ji Techniques Testing Training Transgenic Mice Translational Research Universities Up-Regulation Vascular Diseases Vertebral column Yoga addiction awake bench to bedside central sensitization chronic pain chronic pain patient circulating biomarkers clinically relevant cytokine data acquisition endoplasmic reticulum stress glial activation hydroxyurea imaging approach improved infancy inflammatory milieu mast cell mouse model myoinositol neuroimaging p38 Mitogen Activated Protein Kinase pain reduction pain relief painful neuropathy pharmacologic predicting response programs response restraint sickling side effect tenure track vaso-occlusive crisis

项目摘要

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.

项目摘要/摘要镰状细胞疾病（SCD）的特征是慢性疼痛，有潜在的氧化应激，炎症，缺氧和中央灵敏度。阿片类药物是SCD疼痛疗法的支柱，但通常无效并与重大副作用相关。使用非药物疗法的潜在好处（例如已经报道了针灸，催眠，太极拳，瑜伽），但由于缺乏系统而没有系统地应用令人信服的证据。在SCD的人源化转基因小鼠模型中，电针（EA）为不使用麻醉或约束而进行管理。我们观察到产生的镇痛的个体差异通过EA，疼痛减轻的强度与外周/中心的表达正相关炎症介体。需要探索各种镇痛的基本机制，以便制定一种有效的策略，使较差的响应者对EA的疼痛缓解不足。具体该项目的目的是1）确定特定炎症生物标志物的水平（例如物质 P，TNF-α，IL-1β，IL-6）有助于EA在镰状小鼠中的镇痛作用，2）证明了靶向炎症生物标志物的痛觉过敏的机制阻碍了EA IN的镇痛作用响应者差，3）确定选定循环生物标志物和镰状患者的针灸镇痛程度，以及它们与静止状态的变化的相关程度 fMRI和特定的脑神经代谢物具有针灸的干预。主要目标奖项的指导（K99）部分是为候选人提供神经影像疼痛的全面培训她获得任期教师职位并成功带领她的研究和临床技能自己的独立研究计划。 K99候选人提出的大多数研究和培训阶段将在博士的心态下在明尼苏达大学完成。 Kalpna Gupta，Gregory Vercellotti和Donald Simone与Drs的合作。小山和艾尔兹（Al Beitz）。外部密歇根大学的理查德·哈里斯（Richard Harris）博士的遗产将指导与MRI有关的培训候选人技术。综合医学领先的物理科学家Lonnie Zeltzer博士也将担任咨询公司的联合学者与拟议研究的临床相关方面的候选人与同事 Vercellotti博士。这些导师和顾问是分子/生理学的世界知名专家与SCD/癌症或疼痛神经影像学分别相关的疼痛研究。明尼苏达大学是由于可用的资源，包括承诺的教师，非常适合该项目的K99阶段进行基本和翻译的疼痛研究和心理，研究介绍的磁共振成像（MRI）扫描仪和最先进的疼痛测试设备，以及在部门的大量实验室和办公空间医学和放射学。完成该奖项的K99部分后，候选人将非常适合过渡到终身教师职位。