Neuroimaging Acupuncture Effects Brain Activity in Chronic low Back Pain

描述(申请人提供)：尽管在许多临床试验中，针灸已被证明对慢性下腰痛(CLBP)有效，但目前对于针灸为什么有效仍存在不确定性。在多项试验中，针灸并没有显示出比基于假针刺的安慰剂对照组有显著改善，假针刺可能包括插入或非插入“针刺”，用一个按压皮肤的设备进行。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穴位按压的积极疗法。最终，针灸临床试验产生的这种不确定状态的存在，是因为我们缺乏对真实针灸与各种形式的假针灸背后的作用机制的了解。具体地说，我们不知道针刺和体感传入对cLBP的针刺镇痛机制有多重要。有理由相信真正的针灸可能有不同于假针灸的机制，我们认为神经成像可以提供一个可测试的神经生物学模型，该模型识别有或没有体感传入的针灸治疗的不同作用机制。这些假说将在一种特定的慢性疼痛人群--特发性cLBP上进行测试，这种疼痛具有显著的“中枢”疼痛成分，其特征是异常的躯体动作和增强的大脑对实验性疼痛(痛觉过敏)的反应。CLBP患者的临床疼痛与脑功能的相关性尚未得到很好的描述，但我们自己的数据表明，临床疼痛与疼痛处理脑区(如脑岛)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)，这是一个被认为是自我参照认知的基础网络，并受到针灸的调节。我们认为，真实和不同形式的假针灸对这些网络进行了不同的调制，并改变了体视功能。我们的总体目标是评估辅助cLBP的大脑神经回路是否对有和没有躯体感觉传入的真针刺和假针刺有不同的反应。为了验证我们的特定假设，我们将使用功能磁共振成像(FMRI)来评估cLBP患者为临床和实验疼痛、针灸刺激和体视手术提供服务的大脑网络。这些措施将在基线和7周(A)之后执行。针灸，针灸；(B)假针刺加体感疗法；(C)假针刺无躯体感觉，假毫升或(d.)等待名单，西雅图。目的1描述腰背部疼痛的神经回路，以及腰背部SI体位和脑对针刺刺激的反应。目的2将评估针刺与假SN对cLBP脑网络和SI体位的纵向影响，而目标3将评估Sham-sn与Sham-m1对这些神经影像标志物的纵向影响。了解躯体感觉对针灸安慰剂效应的神经影响将极大地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.