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

描述(申请人提供)：尽管针灸被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相当大的安慰剂效应、剂量不精确以及对治疗的高度可变的个人反应。这些潜在混杂因素背后的机制仍不清楚。同时，脑成像的发展为科学家提供了新的工具来研究针刺治疗的神经生物学机制，并促进了我们对针刺刺激脑效应的理解。然而，到目前为止，大多数针灸神经成像研究都是在健康受试者身上进行的，在单一治疗过程中使用单一的针灸针灸。真正的临床针灸实践和机制研究之间的这种差距严重阻碍了该领域的进步，并限制了这些研究结果的影响。在这项建议中，我们计划使用一种近似于膝骨性关节炎(OA)患者多个治疗过程中的临床针灸实践的范式，动态研究Verum针刺(两种不同的“剂量”)和安慰剂针灸的大脑反应。这项建议的目的是：1)表征真假针刺治疗对骨性关节炎患者的间歇期大脑反应(反应的可靠性)，以及2)研究不同“剂量”的针灸如何影响大脑反应和针灸疗效(剂量的影响)。如果不清楚不同治疗阶段之间针灸反应的差异性以及依赖于针灸“剂量”的差异性，针灸在临床治疗中的潜在效用的研究将受到严重限制。我们已经将针灸治疗骨性关节炎确定为最关键和最紧迫的研究人群，因为针灸对骨性关节炎有着巨大的希望，而且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向前迈出了关键的一步。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，评估该疗法的潜在好处。

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.