Enhancing Physical Therapy: Noninvasive Brain Stimulation System for Treating Carpal Tunnel Syndrome

腕管综合征（CTS）影响高达4%的美国人口，在工作中的患病率更高 人口[1，2]。慢性疼痛（CP）是CTS最常见和最难治疗的并发症之一[2-6]。 目前的治疗方法[2-11]没有直接解决疼痛感觉在大脑中处理的事实[5，12-14]。 并且大多数作用于神经病变部位（即，虽然CTS患者也有中枢性疼痛， #21519;的伤害，[12-15] CTS病理学与CP诱导的脑变化相关 结构与功能[14-24]非侵入性脑刺激（NIBS）已成功应用于 在某些疾病状态下治疗CP，其中治疗诱导的脑活动变化恢复适应不良 与CP的感知/感觉相关的可塑性[25-28]。然而，最常见的NIBS方法， 例如，在一个实施例中，经颅直流电刺激在治疗神经性疼痛中显示出有限的（如果有的话）功效[13， 29-33]。据推测，传统NIBS技术的局限性，穿透力， 靶向控制限制了它们的治疗功效[34-38]。电声刺激（ESStim™）是一种改进的 NIBS模式，通过结合独立控制的 电磁场和超声场，以通过调谐的机电 神经组织中的耦合[39]。该提案的重点是评估我们的无创ESStim系统是否 可以有效地治疗CTS中的CP，无论是作为单独治疗还是与物理治疗（PT）结合。在 第一阶段，评估拟议工作的可行性，并专门测试ESStim改进CTS的能力 疼痛，我们将跟踪20例CTS患者给予固定剂量的ESStim后，连续5天，20分钟/天（10 SHAM ESStim，10 ESStim）。我们将进行一系列安全、疼痛、定量感觉测试（QST）， 运动功能和整体自我评估（例如，QOL）在治疗期间和至少 最后一次治疗后六周。接下来在第二阶段，我们将评估ESStim是否会引起疼痛 减少可以与物理治疗（PT）相结合，以改善CTS治疗。我们将遵循60 CTS 患者（30例ESStim，30例SHAM）在两周内给予固定剂量刺激10天后，20分钟/天， 但现在与PT一起提供。我们将对这些患者进行一系列评估， 在第一阶段验证，并比较测试干预措施的有效性至少八周后， 最后一次治疗我们假设ESStim可以与PT协同提供，因为两者都可以 鼓励可塑性依赖的变化，这可以最大限度地改善CTS患者的无疼痛移动性。在 与CTS处理并行，我们将建立多元线性和广义线性回归模型， 预测CTS患者与疼痛、身体功能和心理社会评估相关的结局， 基线疾病特征的函数。计算工作将用于开发优化的CTS ESStim给药模型。总的来说，我们假设我们将能够开发用于CTS治疗的ESStim™。

Carpal Tunnel Syndrome (CTS) affects up to 4% of the US population, with higher prevalence in the working population [1, 2]. Chronic pain (CP) is one of the most common and difficult to treat complications of CTS [2-6]. Current therapies [2-11] do not directly address the fact that pain sensation is processed in the brain [5, 12-14] and most act at the neuropathy site (i.e., in the periphery), although CTS patients also have a central pain component due to their injury [5, 6, 12-15]. CTS symptomatology correlates with CP-induced changes in brain activity and/or structure [14-24]. Non-Invasive Brain Stimulation (NIBS) has been successfully applied for the treatment of CP in some disease states, where treatment induced changes in brain activity revert maladaptive plasticity associated with the perception/sensation of CP [25-28]. However, the most common NIBS methods, e.g., transcranial direct current stimulation, have shown limited, if any, efficacy in treating neuropathic pain [13, 29-33]. It has been postulated that limitations in conventional NIBS techniques’ focality, penetration, and targeting control limit their therapeutic efficacy [34-38]. 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 [39]. This proposal is focused on evaluating whether our noninvasive ESStim system can effectively treat CP in CTS, both as a lone treatment and in conjunction with physical therapy (PT). In Phase I, to assess the feasibility of the proposed work, and specifically test ESStim’s ability to improve CTS pain, we will follow 20 CTS 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) evaluated over the treatment period and for at least six weeks following the last treatment session. Next in Phase II, we will assess whether ESStim induced pain reductions can be coupled with physical therapy (PT) to improve CTS treatment. We will follow 60 CTS patients (30 ESStim, 30 SHAM) after giving a fixed dose of stimulation for 10 days over two weeks, 20 min/day, but now provided in conjunction with PT. We will evaluate these patients with the 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. We hypothesize ESStim can be provided synergistically with PT, as both can encourage plasticity-dependent changes which could maximally improve a CTS patient’s pain free mobility. In parallel with the CTS treatments, we will build multivariate linear and generalized linear regression models to predict the CTS patient outcomes related to pain, physical function, and psychosocial assessments as a function of baseline disease characteristics. The computational work will be used to develop an optimized CTS ESStim dosing model. Overall, we hypothesize that we will be able to develop ESStim™ for CTS treatment.