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，大脑的结构和功能会发生变化。 此外，慢性疼痛与大脑功能连接中断有关。脊椎 脊髓刺激(SCS)是一种临床可用的非药物治疗方法，用于 慢性疼痛的管理。尽管SCS对许多人来说是有效的，但也有一些人这样做 而不是利益。因此，为了更好地了解SCS背后的大脑机制 慢性疼痛的治疗和开发SCS疗效的脑生物标记物，我们建议评估 对SCS反应的脑功能变化。找到缓解疼痛的大脑信号作为回应 对SCS的了解将提高对SCS如何缓解慢性疼痛的理解，并可能有助于识别 那些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反应的连通性。我们将研究两个 队列：队列1-对正在进行SCS试验期的SCS患者进行幼稚；队列1-长- 长期使用≥患者(植入后6个月)。我们的目标是识别神经生理学大脑 近红外光谱分析在这两种人群中缓解疼痛的特征 和脑电(RS-fNIRS/EEG)。 研究设计：我们将招募患有顽固性慢性神经性疼痛的退伍军人，这些退伍军人目前 在医疗中心内接受临床护理。队列1：患有慢性神经病的个体 对SCS天真并被选为SCS试验期的疼痛患者，作为其临床护理意愿的一部分 参加两次考察访问：在SCS试验开始之前和试验期结束之前。 数据收集将在所有数据收集时间点(T1-T3)保持一致，并包括RS- FNIRS/EEG和临床疼痛测量。队列2：植入有效SCS≥6的参与者 各月将参加相隔24-48小时进行的三次考察访问。将收集数据 在SCS使用期间和SCS冲洗期之后。数据收集在以下方面保持一致 所有数据收集时间点(T1-T4)，包括RS-fNIRS/EEG和临床疼痛测量。两者都有 队列将接受基于感觉异常的SCS。 目的1是表征疼痛缓解的神经生理学(rs-fNIRS/EEG)脑信号。 SCS试验期适用于对SCS天真的慢性神经病理性疼痛患者。目标2是 患者疼痛缓解的神经生理学(RS-fNIRS/EEG)特征 使用SCS 6个月的慢性神经病理性疼痛患者。要解决的结果措施 这两个目标都包括RS-功能连接(RS-fNIRS/EEG)；以及复合临床疼痛 评估将包括数字疼痛评定量表(NPR)、患者报告的结果 测量信息系统-29 Profile v2.1(PROMIS-29)；EQ-5D-5L；患者全球 变化印象(PGIC)；疼痛检测；活动监测。 意义：研究应对SCS的大脑连通性变化将为深入了解 SCS的治疗机制。使用RS-fNIRS/EEG等神经成像方法，可以 易于在临床环境中应用，进一步完善SCS的患者选择可能会有所改善 SCS治疗的结果。这笔赠款将为未来的研究提供初步数据，旨在 开发SCS治疗止痛的生物标记物。

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.