Assessment of EEG Responses to Spinal Cord Stimulation Waveforms in Chronic Pain Patients

慢性疼痛患者对脊髓刺激波形的脑电图反应评估

• 批准号: 10616136
• 负责人: Ilknur Telkes Ergun
• 金额: $ 24.89万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10616136
• 关键词: Achievement; Adult; Advanced Development; Affect; Affective; Alpha Rhythm; American; Beck depression inventory; Biological Markers; Brain; Brain region; Chronic; Clinical; Complex; Conscious; Consensus; Custom; Data; Decision Making; Development; Devices; Economic Burden; Electroencephalography; Esthesia; Frequencies; Future; Goals; Health Expenditures; Healthcare; Hour; Implant; Individual; Intractable Pain; Intraoperative Monitoring; Lead; Link; McGill Pain Scale; Measurement; Measures; Medical; Methodology; Neurostimulation procedures of spinal cord tissue; Numbness; Numeric Rating Scale; Operative Surgical Procedures; Outcome; Outcome Measure; Pain; Pain Measurement; Paresthesia; Patient Self-Report; Patients; Pattern; Persons; Pharmaceutical Preparations; Physiologic pulse; Physiological; Postoperative Period; Refractory; Reporting; Rest; Scanning; Sensory; Shapes; Sleep; Spatial Distribution; Therapeutic; Training; United States Food and Drug Administration; Work; awake; base; chronic neuropathic pain; chronic pain; chronic pain management; chronic pain patient; chronic painful condition; clinical efficacy; clinical risk; cost; disability; efficacy study; experience; implantation; improved; insight; mathematical model; meetings; neural correlate; neural patterning; neurophysiology; neuroregulation; neurotechnology; non-opioid analgesic; novel; pain catastrophizing; pain relief; pain sensation; patient subsets; productivity loss; relating to nervous system; response; sensory gating; somatosensory; success; temporal measurement; tool; treatment response

Chronic pain is a significant problem and it has been estimated to affect about 50 million adult Americans. It accounts for more than 600 billion dollars in health care expenditures, disability and loss of productivity and remains one of the most common reasons that patients seek healthcare. Spinal cord stimulation (SCS) is a Food and Drug Administration (FDA)-approved neuromodulation treatment to relieve chronic refractory pain. While SCS can be used effectively in many patients with refractory chronic pain conditions, a significant portion of the patients receive suboptimal or inadequate pain suppression. Considering that over 30,000 individuals receive SCS implantation on an annual basis for chronic pain and an annual cost of over $24,000 per patient resulting from lack of satisfactory pain relief due to lack of consensus regarding optimal stimulation parameters, it is crucial to improve the clinical efficacy of SCS in chronic refractory pain. Beside the traditional stimulation (tonic), using novel stimulation waveforms such as burst and high frequency stimulation (HFS) is one approach. These waveforms do not induce paresthesia (sensation of tingling or numbness) and their effects are often delayed 24- 48 hours unlike tonic stimulation, where the effects are immediate. However, the supraspinal effects of these waveforms are still not very clear. It is also unknown why some patients respond well to one waveform over another. Another limitation is that assessment of the pain relief by SCS depends almost exclusively on patient self-reports and lack of objective measurements of SCS implants results might lead to increased number of failed permanent placements. In this regard, investigating neural patterns of SCS waveforms and assess SCS-induced pain relief by using electroencephalography (EEG) in awake and anesthetized chronic pain patients appears essential. Our preliminary data suggests that changes in alpha peak frequency and ratio of alpha and theta band power might be correlated to SCS-induced pain relief. The spatial distribution of these patterns is closely related to which waveform is used. We hypothesize that intra-operative EEG demonstrates similar spatio-spectral patterns to post-operative EEG. We predict that pain relief will correlate best with increased alpha band power in frontal and somatosensory regions in burst stimulation and somatosensory cortical regions in HFS. In this proposal, our objectives are to determine the relationship between alpha band features and SCS-induced pain relief in awake patients (Aim 1), determine the spatio-spectral differences between “sleep” and awake states EEG and characterize the intra-operative neural correlates of pain relief (Aim 2), and examine the changes in alpha band features when patients with minimal pain relief are reprogrammed to experience pain relief (Aim 3). Specifically, in Aim 3, we will develop a mathematical model based on these neural features and patients will be temporarily programmed to this EEG-guided setting. We will investigate the predictive power of the assessed neural patterns on selection of the optimal waveform. The immediate goal of this project is to develop quantified, neural signatures of pain relief. These objective markers could form an objective metric for device selection, which might reduce the healthcare expenditures associated with failed implants and help in guiding SCS parameters for better pain relief, especially in patients with minimal pain relief. Overall, these objective neurophysiological measures can be used for more personalized SCS therapy with higher efficacy, and, this study can contribute to development of neurotechnologies and neuroengineering methodologies.

慢性疼痛是一个严重的问题，据估计它影响着大约 5000 万美国成年人。它造成超过 6000 亿美元的医疗保健支出、残疾和生产力损失，并且仍然是患者寻求医疗保健的最常见原因之一。脊髓刺激 (SCS) 是一种经美国食品和药物管理局 (FDA) 批准的神经调节治疗方法，用于缓解慢性难治性疼痛。虽然 SCS 可有效用于许多患有难治性慢性疼痛的患者，但很大一部分患者的疼痛抑制效果不佳或不充分。考虑到每年有超过 30,000 人因慢性疼痛接受 SCS 植入，并且由于对最佳刺激参数缺乏共识而无法令人满意地缓解疼痛，因此每个患者每年的费用超过 24,000 美元，因此提高 SCS 在慢性难治性疼痛中的临床疗效至关重要。除了传统的刺激（强直）之外，使用突发刺激和高频刺激（HFS）等新颖的刺激波形也是一种方法。这些波形不会引起感觉异常（刺痛或麻木的感觉），并且其效果通常会延迟 24-48 小时，这与效果立竿见影的强直刺激不同。然而，这些波形的椎上效应仍然不是很清楚。还不清楚为什么有些患者对一种波形的反应优于另一种波形。另一个限制是，SCS 疼痛缓解的评估几乎完全取决于患者的自我报告，缺乏对 SCS 植入结果的客观测量可能会导致永久植入失败的数量增加。在这方面，研究 SCS 波形的神经模式并通过使用脑电图 (EEG) 对清醒和麻醉的慢性疼痛患者评估 SCS 引起的疼痛缓解显得至关重要。我们的初步数据表明，α 峰值频率以及 α 和 θ 波段功率比的变化可能与 SCS 引起的疼痛缓解相关。这些模式的空间分布与所使用的波形密切相关。我们假设术中脑电图表现出与术后脑电图相似的空间频谱模式。我们预测，疼痛缓解与突发刺激中额叶和体感区域以及 HFS 中体感皮质区域的 α 带功率增加具有最佳相关性。在本提案中，我们的目标是确定清醒患者的α带特征与SCS引起的疼痛缓解之间的关系（目标1），确定“睡眠”和清醒状态脑电图之间的空间频谱差异，并表征疼痛缓解的术中神经相关性（目标2），并检查当疼痛缓解程度最低的患者被重新编程以体验疼痛缓解时α带特征的变化（目标3）。具体来说，在目标 3 中，我们将开发一个基于这些神经特征的数学模型，患者将被暂时编程到这种脑电图引导的设置。我们将研究评估的神经模式对选择最佳波形的预测能力。该项目的近期目标是开发缓解疼痛的量化神经特征。这些客观标记可以形成设备选择的客观指标，这可能会减少与植入失败相关的医疗支出，并有助于指导 SCS 参数以更好地缓解疼痛，特别是对于疼痛缓解程度最低的患者。总体而言，这些客观的神经生理学测量可用于更个性化且疗效更高的 SCS 治疗，并且本研究可有助于神经技术和神经工程方法的发展。