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: 10246692
• 负责人: Laura Dipietro
• 金额: $ 38.83万
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246692
• 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; Placebos; 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; 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.

抽象的。糖尿病神经性疼痛（DNP）是最常见且难以治疗的并发症之一 糖尿病[1，2]。当前的疗法[3-10]并未直接解决以下事实。 大脑[10-13]和大多数在神经病部位（即在外围）作用，尽管DNP患者也有A 由于其受伤而导致的中央疼痛成分[10-13]。 DNP症状与慢性疼痛引起的相关 大脑活动和/或结构的变化[13-19]。非侵入性大脑刺激（NIB）已成功 在某些疾病状态下申请治疗慢性疼痛，在治疗诱导大脑变化 活性恢复了与慢性疼痛感知/感觉有关的不良适应性可塑性[20-23]。然而， 最常见的NIBS方法，经颅磁刺激（TMS）和经颅直流电流 刺激（TDC）在治疗神经性疼痛和DNP方面的效率有限（如果有的话）[12，24-30]。它有 假设这些技术的焦点，渗透和靶向控制的局限性限制了 治疗效率[31-35]。电体刺激（ESSTIM™）是一种改进的Nibs模态，克服了 通过组合独立控制的电磁和超声波，其他技术的局限性 通过在神经组织中调谐的机电耦合聚焦和增强刺激电流的场[36]。这 提案的重点是评估我们的非侵入性埃斯蒂姆系统是否可以有效治疗DNP。首先 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跟随20名DNP患者 连续5天，每天20分钟（10 Sham Esstim，10 Esstim™）。我们将管理电池 安全，疼痛，定量感觉测试（QST），运动功能和全局自我评估（例如，QOL）， 在治疗期间进行了至少六周的评估，患者的行为量度 在上次治疗课程之后。第二阶段，我们将关注40名DNP患者（20个esstim，20个假） 在连续5天，20分钟/天给出了固定剂量的刺激后，然后是三周的双 每周刺激，20分钟/天（总刺激）。我们将用相同的电池评估这些患者 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效率 在上次治疗课程之后。与DNP处理并行，我们将建立MRI派生模型 DNP患者的头部（电场和声场模型）中的刺激场计算 大脑目标部位的刺激场特征。多元线性和广义线性回归 然后将建立和评估模型，以预测与疼痛，身体机能， 和社会心理评估是基线疾病特征和基于MRI的剂量的函数 型号。计算工作将组合起来，以开发优化的DNP ESSTIM剂量模型。全面的， 我们假设拟议的实验，计算研究和技术开发将允许 我们要优化ESSTIM™，以治疗DNP中心疼痛。