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

摘要 慢性下腰痛(CLBP)是医学上最普遍、最棘手的问题之一。 患者痛苦和残疾的重要来源，导致阿片类药物滥用和成瘾。上一首 CLBP的神经调节治疗主要集中在脊髓病因和脊髓内机制。 疼痛传递。然而，现有的药物和神经调节疗法并不成功。 治疗慢性阻塞性肺疾病。潜在的差距和机会包括：(1)需要更好地了解大脑网络 潜在的CLBP，(2)DBS设备的开发，可以更好地针对潜在的特定大脑网络 以安全和临床可测试的方式进行CLBP，以及(3)识别神经成像生物标记物对 CLBP的星展银行。疼痛可以分为感觉成分、认知成分和情感成分。成长性神经成像 有证据表明，慢性疼痛与调节这些的大脑回路的广泛变化有关。 情感成分有特殊病理性过度表现的成分。目前的提案 旨在解决这些关键差距和CLBP患者未得到满足的治疗需求，方法是使用Next- 具有定向引导能力的新一代DBS设备，可与已知的网络接合，以调解 CLBP的情感成分。我们将使用雅培无限™DBS系统，它提供分段 能够提供定向电流转向技术的电极。此外，我们将利用患者- 以膝下扣带皮质(SCC)为靶点的特定概率纤维束造影术 介导慢性疼痛的情感成分的主要纤维通路。SCC区域演示 与下游大脑结构的结构性连接也被认为参与了 慢性疼痛和鳞状细胞癌的DBS此前已被证明对难治性患者的影响有所改善 抑郁症。本申请的目的是提出一项SCC DBS的探索性临床试验 用于治疗难治性CLBP，它利用了我们的多学科专业知识和技术技能。 具体地说，为了开展这项试验，我们提出了以下目标：(1)评估安慰剂的初步疗效 SCC治疗难治性CLBP的DBS；(2)证明SCC的安全性和可行性 用于CLBP的DBS；以及(3)基于扩散张量成像(DTI)的SCC DBS反应蓝图 CLBP。这项概念验证试点试验的总体影响包括验证以下概念： CLBP是由情感脑网络中的病理活动引起的，认为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 CLBP对SCC-DBS反应的神经影像生物标志物。

ABSTRACT 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.