Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and tDCS

 描述(由申请人提供)：慢性疼痛的康复包括针对疼痛体验的所有方面的结构化治疗计划，并应包括一种综合的跨学科方法，使患者能够根据他们的需求获得最大益处。与其他慢性疼痛综合征一样，慢性幻肢痛(PLP)通常难以治疗，对经典的药物和手术治疗方法表现出抵抗力。在治疗PLP方面缺乏疗效是因为目前的康复措施没有考虑到与这种疼痛相关的复杂的潜在神经机制。事实上，广泛的证据表明，慢性PLP是一种与躯体感觉和运动皮质的显著重组有关的现象。止痛药不能抵消导致这些区域不适应可塑性的机制，因此不是最有效的治疗方法。在此背景下，我们假设PLP的新治疗方法需要针对与这种不适应可塑性相关的特定神经网络。经颅直流电刺激(TDC)是一种强大的非侵入性脑刺激技术，可显著调节可塑性，缓解各种症状的慢性疼痛。 最近，我们发现正极tdcs可选择性地缓解PLP，反复应用正极tdcs可产生持久的镇痛效应。这些初步结果表明，tDCs可能是治疗慢性PLP的一种有前途的康复工具。鉴于tDCs潜在的神经机制，使用多模式方法进行治疗至关重要--同时使用tDCs和行为疗法。在这种情况下，理想的治疗方法是镜像疗法(MT)。这种神经康复技术通常用于PLP，旨在通过在镜子前使用未受影响的肢体进行运动来调节皮质疼痛机制。我们建议进行一项机械性、析因、随机对照试验，以评估一种结合tDCs和MT的新康复方法在PLP患者中的应用。我们的目的是比较治疗前后的脑变化，以研究PLP的发病机制。目的1评价tdcs和MT作为康复工具的疗效。患者将被分配到四组中的一组：活动的tdcs/MT组；假的tdcs/MT组；活动的tdcs/sham MT组(隐蔽MT组)；和假tdcs/Sham MT组(隐蔽的MT组)。目标2将研究PLP背后的机制。我们将使用单脉冲和双脉冲经颅磁刺激(TMS)来评估与皮质重组相关的皮质标测和皮质兴奋性变化。我们还将使用功能磁共振成像(FMRI)来评估与这种治疗相关的感觉-运动皮质的大脑反应。这一建议将有助于理解和开发一种新的PLP干预方法，具有重要的意义。斯波尔丁康复医院是包括波士顿马拉松爆炸案中大多数截肢者在内的截肢者康复的主要中心。 相关性：慢性幻肢痛(PLP)被认为非常难以治疗，因为它通常对传统的药物和手术治疗方法具有抵抗力。它是残疾的主要原因，也是生活质量的主要贡献者。广泛的证据表明，PLP是一种与显著的适应不良大脑变化有关的现象。在这项研究中，我们建议探索一种新的康复方法，将行为疗法-镜像疗法-与脑调制方法(Tdcs)相结合来治疗PLP并探讨其机制。

 DESCRIPTION (provided by applicant): Rehabilitation for chronic pain involves a structured treatment plan targeting all dimensions of the pain experience, and should include a comprehensive interdisciplinary approach that allows patients to receive the most benefit according to their needs. As in other chronic pain syndromes, chronic Phantom limb pain (PLP) is often difficult to treat, showing to be resistant to classical pharmacological and surgical treatment approaches. This lack of efficacy in treatment of PLP is because current rehabilitative measures do not take into account the complex underlying neural mechanisms related to this pain. In fact, extensive evidence indicates that chronic PLP is a phenomenon related to a significant reorganization of the somatosensory and motor cortex. Analgesic drugs do not counteract the mechanisms that lead to maladaptive plasticity of these areas, and therefore is not the most efficacious treatment. In this context, we hypothesize that novel treatments of PLP need to target specific neural networks associated with this maladaptive plasticity. Transcranial direct current stimulation (tDCS) is a powerful and non-invasive technique of brain stimulation that is known to significantly modulate plasticity and alleviate chronic pain in various syndromes. Recently, we showed that anodal tDCS can induce a selective short-lasting relief from PLP, and repeated applications of anodal tDCS induces long- lasting analgesic effects. These preliminary results show that tDCS may be a promising rehabilitative tool for the management of chronic PLP. Given tDCS underlying neural mechanisms, it is critical to use a multimodal approach to treatment - using both tDCS and behavioral therapy simultaneously. In this case, an ideal therapy is mirror therapy (MT). This neurorehabilitation technique is commonly used in PLP, and is designed to modulate cortical mechanisms of pain by performing movements using the unaffected limb in front of a mirror. We propose to carry out a mechanistic, factorial, randomized controlled trial to evaluate a novel rehabilitation approach combining tDCS and MT in PLP patients. We aim to compare the brain changes before and after treatment in order to study the mechanisms underlying PLP. Aim 1 will evaluate the efficacy of tDCS and MT as rehabilitative tools. Patients will be assigned to one of four groups: active tDCS/MT; sham tDCS/MT; active tDCS/sham MT (covered MT); and sham tDCS/sham MT (covered MT). Aim 2 will examine the mechanisms underlying PLP. We will use single and paired-pulse transcranial magnetic stimulation (TMS) to assess cortical mapping and cortical excitability changes associated with cortical reorganization. We will also use functional magnetic resonance imaging (fMRI) to assess brain responses in the sensory-motor cortex associated with this treatment. This proposal has a great significance as it will help to understand and develop a novel intervention for PLP. Spaulding Rehabilitation Hospital - where this proposal is being developed - is a major center for rehabilitation of amputees including most of the amputees from the Boston Marathon Bombing. RELEVANCE: Chronic phantom limb pain (PLP) is recognized as very difficult to treat as it is often resistant to classical pharmacological and surgical treatment approaches. It is a major cause of disability and a main contributor to the quality of life. Extensive evidence indicates tha PLP is a phenomenon related to significant maladaptive brain changes. In this study we propose to investigate a novel rehabilitation approach combining a behavioral therapy- mirror therapy- with a method of brain modulation (tDCS) to treat and investigate the mechanisms of PLP.