Neuroimaging Acupuncture Effects Brain Activity in Chronic low Back Pain

描述（由申请人提供）：虽然针灸已被证明是有效的慢性腰痛（cLBP）在许多临床试验中，有一个目前的状态不确定为什么针灸是有效的。在多项试验中，针灸并没有表现出显着改善安慰剂对照的基础上假针刺，这可能涉及插入或非插入“针刺”与设备，压在皮肤上。然而，使用假针刺作为安慰剂对照一直受到批评，因为它可能是一种类似于指压的积极治疗。最后，这种不确定性的状态所产生的针灸临床试验的存在，因为我们缺乏了解的作用机制，潜在的真实的与各种形式的假针灸。具体来说，我们不知道针刺和躯体感觉传入对cLBP的针刺镇痛机制有多重要。有理由相信，真实的针灸可能有不同的机制，从假针灸，我们建议，神经影像学可以告知一个可测试的神经生物学模型，确定不同的作用机制，针灸治疗与无体感传入。这些假设将在一个特定的慢性疼痛人群，特发性cLBP，这有一个显着的“中央”疼痛的组成部分，其特征是异常的躯体和增强的大脑反应实验疼痛（痛觉过敏）。cLBP中临床疼痛的大脑相关性还没有得到很好的表征，但我们自己的数据表明，临床疼痛与疼痛处理脑区域（例如，大脑皮层）和特定的内在连接网络之间的内在功能连接增加有关。这些网络包括执行注意网络（EAN）和“默认模式网络”（DMN），该网络被认为是自我参照认知的基础，并通过针灸进行调节。我们认为，真实的和不同形式的假针灸差异调节这些网络，并改变躯体。我们的总体目标是评估是否大脑神经回路subserving cLBP差异响应真实的与“假”针刺与体感传入。为了验证我们的具体假设，我们将采用功能性磁共振成像（fMRI）来评估cLBP患者的临床和实验疼痛，针刺刺激和躯体功能的脑网络。这些测量将在基线时和（a）7周后进行。针灸，ACUP;（B.）具有躯体感觉的假针灸，SHAM-sn;（c.）假针刺无躯体感觉组（SHAM-ml），d.等待列表，WL。目的1将描述cLBP的疼痛神经回路，以及下背部SI体感，和大脑对针刺刺激的反应。目的2将评价ACUP与SHAM-sn对cLBP中的脑网络和SI躯体适应性的纵向效应，而目的3将评价SHAM-sn与SHAM-ml对这些相同的神经成像标志物的纵向效应。了解躯体感觉对针灸安慰剂效应的神经影响将显著影响我们对针灸的理解，并允许开发更惰性的针灸安慰剂。

DESCRIPTION (provided by applicant): While acupuncture has been shown to be effective for chronic low back pain (cLBP) in many clinical trials, there is a current state of uncertainty as to why acupuncture is effective. In multiple trials, acupuncture does not demonstrate significant improvement over placebo controls based on sham needling, which can involve insertive or non-insertive "needling" with a device that presses against the skin. However, the use of sham needling as placebo control has been criticized since it may be an active therapy akin to acupressure. Ultimately, this state of uncertainty arising from acupuncture clinical trials exists because we lack understanding about the mechanisms of action underlying real versus various forms of sham acupuncture. Specifically, we do not know just how important needle insertion and somatosensory afference are to the mechanisms underlying acupuncture analgesia in cLBP. There is reason to believe that real acupuncture may have different mechanisms from sham acupuncture, and we propose that neuroimaging can inform a testable neurobiological model that identifies diverse mechanisms of action for acupuncture therapy with versus without somatosensory afference. These hypotheses will be tested on a specific chronic pain population, idiopathic cLBP, which has a significant "central" pain component characterized by aberrant somatotopy and augmented brain response to experimental pain (hyperalgesia). The brain correlates of clinical pain in cLBP have been less well characterized, but our own data suggests that clinical pain is associated with increased intrinsic functional connectivity between pain processing brain regions (e.g insula) and specific intrinsic connectivity networks. These networks include the executive attention network (EAN) and "default mode network" (DMN), a network thought to underlie self-referential cognition and modulated by acupuncture. We propose that real and different forms of sham acupuncture differentially modulate these networks, and alter somatotopy. Our overall goal is to evaluate whether the brain neurocircuitry subserving cLBP responds differentially to real versus "sham" acupuncture with and without somatosensory afference. To test our specific hypotheses, we will employ functional magnetic resonance imaging (fMRI) to assess brain networks subserving both clinical and experimental pain, acupuncture stimulation, and somatotopy in cLBP patients. These measures will be performed at baseline and following 7 weeks of (a.) acupuncture, ACUP; (b.) sham acupuncture with somatosensation, SHAM-sn; (c.) sham acupuncture without somatosensation, SHAM-ml\ or (d.) wait list, WL. Aim 1 will characterize the pain neurocircuitry in cLBP, as well as low back SI somatotopy, and brain response to acupuncture stimuli. Aim 2 will evaluate longitudinal effects of ACUP vs. SHAM-sn on brain networks and SI somatotopy in cLBP, while Aim 3 will evaluate the longitudinal effects of SHAM-sn vs. SHAM-ml on these same neuroimaging markers. Understanding the neural influence of somatosensation on acupuncture placebo effects will significantly impact our understanding of acupuncture and allow for development of more inert acupuncture placebos.