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，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，慢性疼痛与功能性大脑连接的中断有关。脊柱 脊髓刺激（SCS）是一种临床上可用的非药物疗法，用于 管理慢性疼痛。虽然SCS对许多人有效，但也有一些人 而不是利益。因此，为了更好地理解SCS的大脑机制， 治疗慢性疼痛和开发SCS疗效的脑生物标志物，我们建议评估 功能性脑变化对SCS的反应。找到缓解疼痛的大脑信号 SCS将提高对SCS如何缓解慢性疼痛的理解， 最有可能回应的人。这项研究的主要目的是评估大脑的变化， 慢性神经性疼痛患者对SCS的连接反应。我们将研究两个 队列：队列1-接受SCS试验期的SCS初治患者;队列1-长期- 长期SCS使用者（植入后≥ 6个月）。我们的目标是从神经生理学的角度 使用静息状态近红外光谱分析这两个人群的疼痛缓解特征 和脑电图（rs-fNIRS/EEG）。 研究设计：我们将招募目前患有难治性慢性神经性疼痛的退伍军人， 在医疗中心接受临床护理。队列1：慢性神经病患者 未接受过SCS治疗并作为其临床护理的一部分选择接受SCS试验的疼痛患者将 参加两次研究访视：SCS试验开始前和试验期结束前。 所有数据采集时间点（T1-T3）的数据采集将保持一致，包括rs- fNIRS/EEG和临床疼痛测量。队列2：有效植入SCS ≥ 6的受试者 每个月将参加三次研究访视，间隔24 - 48小时。数据将被收集 在SCS使用期间和SCS洗脱期之后。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 队列将接受基于感觉异常的SCS。 目的1是表征疼痛缓解过程中的神经生理学（rs-fNIRS/EEG）脑特征， 未接受过SCS治疗的慢性神经性疼痛患者的SCS试验期。目标2是 表征患者疼痛缓解的神经生理学（rs-fNIRS/EEG）脑特征 使用SCS ≥ 6个月的慢性神经性疼痛患者。解决措施 这两个目标包括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）、患者报告结局 测量信息系统-29 profile v2.1（PROMIS-29）; EQ-5D-5L;患者全局 变化印象（PGIC）; painDetect;和活动监测。 意义：研究大脑连接对SCS的反应变化将提供对以下方面的深入了解： SCS的治疗机制。使用神经成像方法，如rs-fNIRS/EEG， 易于在临床环境中应用，以进一步完善SCS的患者选择， SCS治疗的结果。这笔赠款将为今后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.