An acupuncture fMRI study on chronic pain: response reliability and dose effect

描述（由申请人提供）：尽管针灸用于缓解疼痛已有数千年的历史，但最近研究其对慢性疼痛疗效的临床试验显示出相互矛盾的结果。这种模糊性可能源于针灸的相当大的安慰剂效应，剂量不精确以及高度可变的个体对治疗的反应。这些潜在混杂因素背后的机制尚不清楚。与此同时，脑成像技术的发展为科学家研究针灸治疗的神经生物学机制提供了新的工具，并促进了我们对针灸刺激对大脑影响的理解。然而，迄今为止，大多数针灸神经影像学研究都是在健康受试者上进行的，在一次治疗中使用一根针灸针。实际临床针灸实践与机制研究之间的差距极大地阻碍了该领域的进展，并限制了这些研究结果的意义。在这个提议中，我们计划动态研究脑对verum针灸（两种不同“剂量”）和安慰剂针灸的反应，使用一个接近临床针灸治疗膝关节骨关节炎（OA）患者的多个治疗阶段的范例。本研究旨在：1)表征OA患者对verum / sham针灸治疗的脑反应（反应可靠性）；2)研究不同“剂量”针灸对脑反应和针灸疗效的影响（剂量的影响）。如果对不同治疗阶段之间针灸反应的可变性以及针灸“剂量”的可变性没有如此清晰的机制理解，针灸在临床护理中的潜在效用的调查将受到严重限制。我们已经确定针灸治疗OA是最关键和最紧迫的研究人群，因为针灸对OA有很大的希望，迫切需要澄清为什么精心设计的针灸临床试验产生了相互矛盾的结果。我们相信这项研究在将脑成像工具应用于针灸临床研究方面迈出了关键的一步。这将有助于加深我们对针灸机制的生物学理解，并完善未来的临床研究方案，评估该疗法的潜在益处。

DESCRIPTION (provided by applicant): Although acupuncture has been used to relieve pain for thousands of years, recent clinical trials investigating its efficacy on chronic pain have shown contradictory results. This ambiguity may derive from acupuncture's sizeable placebo effects, dosage imprecision as well as highly variable individual response to treatment. The mechanisms underlying these potential confounders remain unknown. In parallel, development in brain imaging provide scientists with new tools for investigating the neurobiological mechanisms underlying acupuncture treatment, and have advanced our understanding of the brain effects of acupuncture stimulation. However, most acupuncture neuroimaging studies to date have been conducted on healthy subjects using a single acupuncture needle in a single treatment session. This gap between the real clinical acupuncture practice and mechanistic research significantly hinders progress in the field and limits the implications of these research findings. In this proposal, we plan to dynamically investigate brain response to verum acupuncture (of two different "doses") and placebo acupuncture, using a paradigm that approximates clinical acupuncture practice across multiple treatment sessions in knee osteoarthritis (OA) patients. This proposal aims to: 1) characterize session-to-session brain responses to verum / sham acupuncture treatment (reliability of response) for OA patients, and 2) investigate how different "doses" of acupuncture influence brain response and acupuncture efficacy (impact of dose). Without such a clear mechanistic understanding of the variability in acupuncture response between different treatment sessions and the variability dependent on acupuncture "dosage," investigation of acupuncture's potential utility for clinical care will be severely limited. We have identified acupuncture treatment for OA as the most critical and urgent study population because acupuncture holds great promise for OA and there is a pressing need to clarify why well-designed acupuncture clinical trials have produced contradictory results. We believe this research takes a critical step forward in applying brain imaging tools to clinical studies of acupuncture. It will help deepen our biological understanding of acupuncture mechanisms and refine future clinical research protocols evaluating the therapy's potential benefits.