Beth Israel Hospital/Harvard Medical School, Boston, MA 02139, USA.
Contributed equally.
BMJ. 2020 Jul 20;370:m1668. doi: 10.1136/bmj.m1668.
Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this review examines the effect of placebo treatment under three distinct frameworks: double blind, deception, and open label honestly prescribed. These specific conditions do not necessarily differentially modify placebo outcomes. Psychological, clinical, and neurological theories of placebo effects are scrutinized. In chronic pain, conscious expectation does not reliably predict placebo effects. A supportive patient-physician relationship may enhance placebo effects. This review highlights "predictive coding" and "bayesian brain" as emerging models derived from computational neurobiology that offer a unified framework to explain the heterogeneous evidence on placebos. These models invert the dogma of the brain as a stimulus driven organ to one in which perception relies heavily on learnt, top down, cortical predictions to infer the source of incoming sensory data. In predictive coding/bayesian brain, both chronic pain (significantly modulated by central sensitization) and its alleviation with placebo treatment are explicated as centrally encoded, mostly non-conscious, bayesian biases. The review then evaluates seven ways in which placebos are used in clinical practice and research and their bioethical implications. In this way, it shows that placebo effects are evidence based, clinically relevant, and potentially ethical tools for relieving chronic pain.
尽管安慰剂和安慰剂效应无处不在，但它们在生物医学中仍然存在着模糊和令人不安的存在。本综述特别关注慢性疼痛，考察了安慰剂治疗在三种不同框架下的效果：双盲、欺骗和开放标签如实处方。这些特定条件不一定会使安慰剂的效果产生差异。对安慰剂效应的心理、临床和神经学理论进行了仔细审查。在慢性疼痛中，有意识的期望并不能可靠地预测安慰剂效应。支持性的医患关系可能会增强安慰剂效应。本综述强调了“预测编码”和“贝叶斯大脑”作为新兴模型，这些模型源自计算神经生物学，为解释关于安慰剂的异质证据提供了一个统一的框架。这些模型颠覆了大脑作为受刺激驱动器官的教条，转而认为感知在很大程度上依赖于习得的、自上而下的皮层预测，以推断传入感觉数据的来源。在预测编码/贝叶斯大脑中，慢性疼痛（受中枢敏化显著调节）及其通过安慰剂治疗缓解都被解释为中枢编码的、主要是无意识的、贝叶斯偏见。然后，本综述评估了安慰剂在临床实践和研究中的七种用途及其生物伦理含义。通过这种方式，它表明安慰剂效应是基于证据的、临床相关的、缓解慢性疼痛的潜在伦理工具。
