Neuroimaging Acupuncture Effects Brain Activity in Chronic low Back Pain

描述（由申请人提供）：虽然针灸在许多临床试验中已被证明对慢性腰痛（cLBP）有效，但目前针灸有效的原因尚不确定。在多次试验中，针灸并没有显示出与基于假针刺的安慰剂对照相比有显著改善。假针刺包括用一种压在皮肤上的装置插入或非插入“针刺”。然而，使用假针刺作为安慰剂控制一直受到批评，因为它可能是一种类似于指压的积极治疗。最终，针灸临床试验中出现的这种不确定性状态的存在是因为我们缺乏对真实针灸和各种形式的假针灸的作用机制的理解。具体地说，我们不知道针的插入和体感传入在cLBP针刺镇痛的机制中有多重要。我们有理由相信，真正的针灸可能与假针灸有不同的机制，我们提出，神经影像学可以为一个可测试的神经生物学模型提供信息，以确定有或没有体感传入的针灸治疗的不同作用机制。这些假设将在一个特定的慢性疼痛人群中进行检验，特发性cLBP具有显著的“中枢”疼痛成分，其特征是异常的躯体解剖和大脑对实验性疼痛（痛觉过敏）的反应增强。cLBP患者临床疼痛的脑相关性尚未得到很好的表征，但我们自己的数据表明，临床疼痛与疼痛处理大脑区域（如脑岛）和特定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），后者被认为是自我参照认知的基础，并由针灸调节。我们提出，真实的和不同形式的假针灸不同地调节这些网络，并改变躯体解剖。我们的总体目标是评估治疗cLBP的脑神经回路对有或无体感传入的真针刺和假针刺是否有不同的反应。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患者在临床和实验疼痛、针灸刺激和躯体切除方面的脑网络。这些措施将在基线和7周后(a)针灸，ACUP；(b)体感假针灸，sham -sn；(c)无体感的假针灸，sham -ml\或(d)等待名单，WL。目的1将描述cLBP的疼痛神经回路，以及腰背SI躯体解剖和大脑对针灸刺激的反应。Aim 2将评估ACUP与SHAM-sn对cLBP脑网络和SI躯体解剖的纵向影响，而Aim 3将评估SHAM-sn与SHAM-ml对这些相同神经影像学标志物的纵向影响。了解躯体感觉对针灸安慰剂效应的神经影响将显著影响我们对针灸的理解，并允许开发更多的惰性针灸安慰剂。

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.