Optimization of Non Invasive Brain Stimulation for Diabetic Neuropathic Pain

无创脑刺激治疗糖尿病神经病理性疼痛的优化

• 批准号: 10316269
• 负责人: Laura Dipietro
• 金额: $ 40.51万
• 依托单位: HIGHLAND INSTRUMENTS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-10 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10316269
• 关键词: Acoustics; Address; Aftercare; American; Area; Behavior; Biophysics; Brain; Brief Pain Inventory; Characteristics; Clinic; Clinical; Complications of Diabetes Mellitus; Coupling; Development; Diabetes Mellitus; Disease; Dose; Double-Blind Method; Effectiveness; Electromagnetics; Electrophysiology (science); Equilibrium; Equipment and supply inventories; Esthesia; Foundations; Head; Health Surveys; Home; Injury; Intervention; Knee Osteoarthritis; Linear Regressions; Magnetic Resonance Imaging; Measures; Methods; Modality; Modeling; Morbidity - disease rate; Motor; Motor Cortex; Neurologic; Neuropathy; Pain; Pain management; Patient-Focused Outcomes; Patients; Penetration; Perception; Phase; Physical Function; Placebo Control; Procedures; Process; Psychosocial Assessment and Care; Quality of life; Randomized; SF-36; Safety; Self Assessment; Sensory; Site; Sleep; Stratification; Structure; System; Techniques; Technology; Testing; Therapeutic Effect; Tissues; Transcranial magnetic stimulation; Treatment Efficacy; Ultrasonics; United States; Work; actigraphy; base; behavioral study; central pain; chronic pain; chronic pain management; comparative efficacy; computer studies; diabetic; diaries; efficacy testing; experimental study; functional outcomes; improved; metabolic abnormality assessment; mortality; noninvasive brain stimulation; novel; outcome prediction; overtreatment; pain outcome; pain patient; pain reduction; pain sensation; pain symptom; painful neuropathy; prognostic; psychosocial; relating to nervous system; safety assessment; symptom treatment; symptomatology; technology development; treatment duration; vector

Abstract. Diabetic neuropathic pain (DNP) is one of the most common and difficult to treat complications of diabetes [1, 2]. Current therapies [3-10] do not directly address the fact that pain sensation is processed in the brain [10-13] and most act at the neuropathy site (i.e., in the periphery), although DNP patients also have a central pain component due to their injury [10-13]. DNP symptomatology correlates with chronic pain induced changes in brain activity and/or structure [13-19]. Non-Invasive Brain Stimulation (NIBS) has been successfully applied for the treatment of chronic pain in some disease states, where treatment induced changes in brain activity revert maladaptive plasticity associated with the perception/sensation of chronic pain [20-23]. However, the most common NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), have shown limited, if any, efficacy in treating neuropathic pain and DNP [12, 24-30]. It has been postulated that limitations in these techniques' focality, penetration, and targeting control limit their therapeutic efficacy [31-35]. Electrosonic Stimulation (ESStim™) is an improved NIBS modality that overcomes the limitations of other technologies by combining independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue [36]. This proposal is focused on evaluating whether our noninvasive ESStim system can effectively treat DNP. First in Phase I, to assess the feasibility of the proposed work, we will follow 20 DNP patients after giving a fixed dose of ESStim for 5 consecutive days, 20 min/day (10 SHAM ESStim, 10 ESStim™). We will administer a battery of safety, pain, quantitative sensory testing (QST), motor function, and global self-assessments (e.g., QOL), and actigraphy measures in the patients, evaluated over the treatment period and for at least six weeks following the last treatment session. Next in Phase II, we will follow 40 DNP patients (20 ESStim, 20 SHAM) after giving a fixed dose of stimulation for 5 consecutive days, 20 min/day, followed by three weeks of bi- weekly stimulation, 20 min/day (11 total stimulations). We will evaluate these patients with the same battery of assessments validated in Phase I, and compare the efficacy of the tested interventions for at least eight weeks following the last treatment session. In parallel with the DNP treatments, we will build MRI derived models of the stimulation fields in the heads (electric and acoustic field models) of the DNP patients to calculate the stimulation field characteristics at the brain target sites. Multivariate linear and generalized linear regression models will then be built and evaluated to predict the DNP patient outcomes related to pain, physical function, and psychosocial assessments as a function of baseline disease characteristics and the MRI based dosing models. The computational work will be combined to develop an optimized DNP ESStim dosing model. Overall, we hypothesize that the proposed experiments, computational studies, and technology development will allow us to optimize ESStim™ for treatment of central pain in DNP.

抽象。糖尿病神经性疼痛（DNP）是糖尿病最常见和最难治疗的并发症之一。 糖尿病[1，2]。目前的治疗[3-10]没有直接解决疼痛感觉在大脑皮层中处理的事实。 脑[10-13]并且大多数作用于神经病变部位（即，在外周），尽管DNP患者也有 由于其损伤的中枢疼痛成分[10-13]。DNP病理学与慢性疼痛诱导的 大脑活动和/或结构的变化[13-19]。非侵入性脑刺激（NIBS）已成功 应用于治疗某些疾病状态下的慢性疼痛，其中治疗引起大脑变化 活动恢复与慢性疼痛的感知/感觉相关的适应不良可塑性[20-23]。然而，在这方面， 最常见的NIBS方法，经颅磁刺激（TMS）和经颅直流电 刺激（tDCS）在治疗神经性疼痛和DNP中显示出有限的（如果有的话）功效[12，24-30]。它有 据推测，这些技术的聚焦性、穿透性和靶向控制的局限性限制了它们的应用。 治疗效果[31-35]。超声电刺激（ESStim™）是一种改进的NIBS模式，克服了 通过结合独立控制的电磁和超声波， 场，以通过神经组织中的调谐机电耦合来聚焦和提升刺激电流[36]。这 该提案的重点是评估我们的非侵入性ESStim系统是否可以有效治疗DNP。第一 第一阶段，为了评估拟议工作的可行性，我们将在给予固定剂量后随访20名DNP患者 连续5天，20分钟/天（10个假ESStim，10个ESStim™）。我们会用电池 安全性、疼痛、定量感觉测试（QST）、运动功能和整体自我评估（例如，生活质量）， 在治疗期间和至少六周内对患者进行评估 在最后一次治疗之后。接下来在II期，我们将随访40例DNP患者（20例ESStim，20例SHAM） 在给予固定剂量的刺激连续5天后，20分钟/天，随后是3周的双- 每周刺激，20分钟/天（共11次刺激）。我们将用相同的一组测试来评估这些患者， 在第一阶段验证的评估，并比较至少八周的测试干预措施的疗效 在最后一次治疗之后。在DNP治疗的同时，我们将建立MRI衍生模型， DNP患者头部的刺激场（电场和声场模型），以计算 在大脑目标部位的刺激场特性。多元线性和广义线性回归 然后将建立模型并进行评估，以预测与疼痛，身体功能， 和心理社会评估作为基线疾病特征和基于MRI的给药的函数 模型将结合计算工作开发优化的DNP ESStim给药模型。总的来说， 我们假设，所提出的实验、计算研究和技术开发将允许 我们将优化ESStim™用于治疗DNP的中枢性疼痛。