Deep Brain Stimulation of the Subgenual Cingulate Cortex for the Treatment of Medically Refractory Chronic Low Back Pain

膝下扣带皮层脑深部刺激治疗难治性慢性腰痛

• 批准号: 10174456
• 负责人: AUSAF BARI
• 金额: $ 14.82万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10174456
• 关键词: Acute Pain; Address; Affect; Affective; Area; Brain; Characteristics; Chronic low back pain; Clinical; Clinical Trials; Cognitive; Conduct Clinical Trials; Crossover Design; Deep Brain Stimulation; Development; Devices; Diagnosis; Diffusion Magnetic Resonance Imaging; Dimensions; Double-Blind Method; Effectiveness; Electrodes; Etiology; Fiber; Forcep; Goals; Literature; Mediating; Medical; Medicine; Mental Depression; Minor; Monitor; Neurostimulation procedures of spinal cord tissue; Neurosurgeon; Opiate Addiction; Opioid; Outcome Assessment; Pain; Pain management; Participant; Pathologic; Pathway interactions; Patients; Pharmacology; Phase; Physicians; Procedures; Quality of life; Quality-of-Life Assessment; Randomized; Refractory; Research Design; Rest; Safety; Seeds; Sensory; Serious Adverse Event; Source; Specialist; Spinal; Structure; System; Technical Expertise; Technology; Therapeutic; United States; Validation; Visit; Visual; analog; anxiety symptoms; arm; base; chronic pain; cingulate cortex; disability; effective therapy; experience; first-in-human; improved; indexing; multidisciplinary; neuroimaging; neuroimaging marker; neuroregulation; next generation; open label; opioid epidemic; opioid misuse; opioid use; pain patient; parent grant; pilot trial; predicting response; primary outcome; response; response biomarker; safety and feasibility; secondary outcome; side effect; tractography; transmission process; white matter

ABSTRACT (Parent Grant) Chronic low back pain (CLBP) is one of the most ubiquitous and intractable problems in medicine and a significant source of patient suffering and disability, leading to opioid misuse and addiction. Previous neuromodulatory therapies for CLBP have focused primarily on spinal etiologies and intra-spinal mechanisms of pain transmission. However, existing pharmacological and neuromodulatory therapies have not been successful in treating CLBP. Potential gaps and opportunities include: (1) a need to better understand the brain networks underlying CLBP, (2) development of DBS devices that can better target the specific brain networks underlying CLBP in a safe and clinically testable manner, and (3) identification of neuroimaging biomarkers of response to DBS for CLBP. Pain can be separated into sensory, cognitive and affect components. Growing neuroimaging evidence shows that chronic pain is associated with widespread changes in brain circuits mediating these components with particular pathological overrepresentation of the affective component. The current proposal aims to address these critical gaps and the unmet therapeutic needs of CLBP patients by using a next- generation DBS device with directional steering capability to engage networks known to mediate the affective component of CLBP. We will use the Abbott Infinity™ DBS System, which offers segmented electrodes capable of providing directional current steering technology. In addition, we will utilize patient- specific probabilistic tractography to target the subgenual cingulate cortex (SCC) in order to engage the major fiber pathways mediating the affective component of chronic pain. The SCC region demonstrates structural connectivity to downstream brain structures also known to be involved in the affective component of chronic pain, and DBS of the SCC has been previously shown to improve affect in patients with intractable depression. The objective of this application is to propose an exploratory first-in-human clinical trial of SCC DBS for the treatment of medically refractory CLBP which leverages our multidisciplinary expertise and technical skills. Specifically, we propose the following aims in order to carry out this trial: (1) Assess the preliminary efficacy of DBS of the SCC in the treatment of medically refractory CLBP; (2) Demonstrate the safety and feasibility of SCC DBS for CLBP; and (3) Develop diffusion tensor imaging (DTI)-based blueprints of response to SCC DBS for CLBP. The overall impact of this proof-of-concept pilot trial includes validation of the concept that suffering from CLBP results from pathological activity in affective brain networks, that these networks can be accurately engaged using a next-generation directional DBS device in a safe and feasible manner, and the discovery of neuroimaging biomarkers of response to SCC DBS for CLBP.

摘要（家长补助金） 慢性腰痛（CLBP）是医学上最普遍和最棘手的问题之一， 这是患者痛苦和残疾的重要来源，导致阿片类药物滥用和成瘾。先前 CLBP的神经调节疗法主要集中在脊髓病因学和脊髓内机制， 疼痛传递然而，现有的药理学和神经调节疗法尚未成功 治疗CLBP。潜在的差距和机会包括：（1）需要更好地了解大脑网络 基础CLBP，（2）开发能够更好地针对基础特定大脑网络的DBS设备 CLBP以安全和临床可测试的方式，和（3）识别响应于CLBP的神经成像生物标志物， DBS用于CLBP。疼痛可以分为感觉、认知和情感成分。生长神经影像学 证据表明，慢性疼痛与介导这些疼痛的大脑回路的广泛变化有关 情感成分具有特别病理性过度表现的成分。现时的建议 旨在通过使用下一个- 具有定向转向能力的第二代DBS设备，以接合已知的调解 CLBP的情感成分。我们将使用Abbott Infinity™ DBS系统， 能够提供定向电流导引技术的电极。此外，我们将利用患者- 特定的概率纤维束成像，以靶向膝下扣带皮层（SCC），以参与 调节慢性疼痛的情感成分的主要纤维通路。SCC区域显示 与下游大脑结构的结构连接也被认为涉及情感成分， 慢性疼痛，并且SCC的DBS先前已被证明可以改善难治性疼痛患者的影响。 萧条本申请的目的是提出SCC DBS的探索性首次人体临床试验 利用我们的多学科专业知识和技术技能治疗医学难治性CLBP。 具体而言，我们提出了以下目的，以进行这项试验：（1）评估初步疗效 DBS治疗难治性CLBP的SCC;（2）证明SCC的安全性和可行性 DBS用于CLBP;（3）开发基于扩散张量成像（DTI）的SCC DBS响应蓝图， CLBP。这一概念验证试验的总体影响包括验证以下概念： CLBP源于情感大脑网络的病理活动，这些网络可以准确地 以安全可行的方式使用下一代定向DBS设备，并发现 神经影像学生物标志物对SCC DBS治疗CLBP的反应。