Brain Connectivity Changes with Spinal Cord Stimulation Treatment of Chronic Pain: A Resting State NIRS/EEG Study

慢性疼痛是一种复杂的神经系统疾病，会对功能和生活质量产生不利影响。 当一个人处于慢性疼痛状态时，大脑结构和功能会发生改变。 此外，慢性疼痛与大脑功能连接的破坏有关。脊柱 脊髓刺激（SCS）是一种临床可用的非药物疗法，用于 慢性疼痛的管理。尽管 SCS 对许多人都有效，但也有一些人不这样做 没有好处。因此，为了更好地理解SCS背后的大脑机制 治疗慢性疼痛并开发 SCS 功效的大脑生物标志物，我们建议评估 大脑功能随 SCS 的变化而变化。寻找缓解疼痛的大脑反应信号 SCS 将提高对 SCS 如何减轻慢性疼痛的理解，并可能有助于识别 最有可能做出回应的人。这项研究的主要目的是评估大脑的变化 慢性神经病理性疼痛患者对 SCS 的反应连通性。我们将学习两个 队列：队列 1——接受 SCS 试验期的 SCS 患者；第 1 组——长—— 足月 SCS 用户（植入后≥6 个月）。我们的目标是识别大脑的神经生理学 使用静息状态近红外光谱对这两个人群的疼痛缓解特征 和脑电图（rs-fNIRS/EEG）。 研究设计：我们将招募患有难治性慢性神经性疼痛的退伍军人，他们目前正在接受治疗 在医疗中心接受临床护理。第 1 组：慢性神经病患者 未接触过 SCS 并被选为 SCS 试验期作为临床护理一部分的患者将 参加两次研究访问：SCS 试验开始前和试验期结束前。 数据收集将在所有数据收集时间点 (T1 – T3) 上保持一致，并包括 rs- fNIRS/EEG 和临床疼痛测量。第 2 组：有效植入 SCS ≥ 6 的参与者 个月将参加 3 次研究访问，间隔 24-48 小时进行。将收集数据 在 SCS 使用期间和 SCS 清洗期之后。数据收集将保持一致 所有数据收集时间点（T1-T4），包括 rs-fNIRS/EEG 和临床疼痛测量。两者都 队列将接受基于感觉异常的 SCS。 目标 1 是表征疼痛缓解期间的神经生理学 (rs-fNIRS/EEG) 大脑特征 SCS 试验期适用于未接受过 SCS 的慢性神经性疼痛患者。目标 2 是 表征疼痛缓解患者的神经生理学 (rs-fNIRS/EEG) 大脑特征 使用 SCS ≥6 个月的慢性神经性疼痛。成果 解决措施 这两个目标都包括 rs 功能连接 (rs-fNIRS/EEG)；和复合临床疼痛 评估将包括数字疼痛评定量表 (NPRS)、患者报告结果 测量信息系统-29配置文件v2.1(PROMIS-29)； EQ-5D-5L；全球患者 变革印象（PGIC）；疼痛检测；和活动监控。 意义：研究 SCS 引起的大脑连接变化将有助于深入了解 SCS的治疗机制。使用 rs-fNIRS/EEG 等神经影像方法 易于应用于临床环境，进一步细化 SCS 的患者选择可能会改善 SCS 治疗的结果。这笔赠款将为未来的研究提供初步数据 开发 SCS 治疗缓解疼痛的生物标志物。

Chronic pain is a complex neurological disease that adversely impacts function and quality of life. Brain structure and function are altered when an individual is in the chronic pain state. Furthermore, chronic pain is associated with disruptions in functional brain connectivity. Spinal cord stimulation (SCS) is a clinically available non-pharmacological therapy that is used in the management of chronic pain. Although SCS is effective for many, there are individuals who do not benefit. Therefore, in order to better understand brain mechanisms that underlie SCS treatment of chronic pain and to develop brain biomarkers of SCS efficacy, we propose to evaluate functional brain changes in response to SCS. Finding a brain signature of pain relief in response to SCS would improve understanding of how SCS alleviates chronic pain and may help to identify those most likely to respond. The main objective of this study is to assess changes in brain connectivity in response to SCS in individuals with chronic neuropathic pain. We will study two cohorts: Cohort 1 – naive to SCS patients who are undergoing SCS trial period; Cohort 1 – long- term SCS users (≥6 months post implantation). We aim to identify neurophysiological brain signatures of pain relief in these two populations using resting state Near Infrared Spectroscopy and Electroencephalography (rs-fNIRS/EEG). Study Design: We will enroll veterans with refractory chronic neuropathic pain who are currently receiving clinical care within the medical center. Cohort 1: Individuals with chronic neuropathic pain who are naïve to SCS and were selected for SCS trial period as part of their clinical care will participate in two study visits: before the beginning of the SCS trial and the end of the trial period. Data collection will be consistent across all data collection timepoints (T1 – T3) and include rs- fNIRS/EEG and clinical pain measures. Cohort 2: Participants with effective implanted SCS ≥ 6 months will participate in three study visits conducted 24-48 hours apart. Data will be collected during SCS use and following an SCS washout period. Data collection will be consistent across all data collection timepoints(T1-T4) and include rs-fNIRS/EEG and clinical pain measures. Both cohorts will receive paresthesia based SCS. AIM 1 is to characterize neurophysiological (rs-fNIRS/EEG) brain signature of pain relief during the SCS trial period for patients with chronic neuropathic pain who are naïve to SCS. AIM 2 is to characterize neurophysiological (rs-fNIRS/EEG) brain signature of pain relief in patients with chronic neuropathic pain who have utilized SCS for ≥6 months. Outcome Measures to address both aims include rs-functional connectivity (rs-fNIRS/EEG); and a composite clinical pain assessment that will include Numeric Pain Rating Scale (NPRS), Patient Reported Outcomes Measurement Information System-29 profile v2.1(PROMIS-29); EQ-5D-5L; Patient Global Impression of Change (PGIC); painDetect; and activity monitoring. Significance: Studying changes in brain connectivity in response to SCS will provide insight into the treatment mechanism of SCS. Use of neuroimaging methods such as rs-fNIRS/EEG that can be easily applied in the clinical setting to further refine patient selection for SCS may improve outcome in SCS therapy. This grant will provide preliminary data for future studies aimed at developing biomarkers of pain-relief with SCS treatment.