Department of Anesthesiology, Pain Research Center, Utah Center for Exploring Mind-Body Interactions (UCEMBI), University of Utah School of Medicine, Salt Lake City, UT, USA.
Pain. 2012 Jan;153(1):227-237. doi: 10.1016/j.pain.2011.10.024. Epub 2011 Nov 21.
Investigating dose-dependent effects of placebo analgesia (PA) in laboratory subjects undergoing pain testing, we evaluated 2 hypotheses: (1) greater expectancy for relief produces greater PA, and (2) cued expectancy for relief triggered by a predictive cue leads to more enhanced analgesia than does passive expectancy (no predictive cue). We used conditioning procedures in which 84 subjects experienced reduced stimulation intensity following the application of purported analgesic creams to the 2 experimental fingers, while the control finger received the same levels of stimulation as in the baseline block. The dose of placebos was manipulated by creating 2 levels of expectations for relief. The form of expectation (cued vs uncued) was also manipulated by a predictive cue specifying the next finger to be stimulated. Subjective reports and psychophysiological responses served as critical indicators for evaluating impacts of the placebo manipulation on subsequent pain processing. The dose-dependent PA was unambiguously demonstrated by the predicted ordering of the 3 fingers (ie, manipulated expectation levels) in terms of both response sensitivity and average response magnitude, in mixed-effects analysis of 3 outcome indicators (evoked potential, skin conductance response, pain report). Greater expectation for relief led to both (1) greater reductions in the average dependent variable slope (response sensitivity) as a function of stimulus intensity, and (2) greater reductions in average response magnitude. Unexpectedly, uncued expectation led to a slightly larger PA than did cued expectation. The study provided clear evidence that PA can occur in a "dose"-dependent manner, mediated by the levels of expectancy for pain relief.
在进行疼痛测试的实验室受试者中，我们调查了安慰剂镇痛（PA）的剂量依赖性效应，评估了两个假设：（1）对缓解的期望越大，PA 越大；（2）由预测线索触发的暗示性缓解期望比被动性缓解期望（无预测线索）产生更大的镇痛增强作用。我们使用了条件作用程序，其中 84 名受试者在将所谓的镇痛乳膏施加到两个实验手指上后，经历了刺激强度的降低，而对照手指则接受了与基线块相同水平的刺激。通过创建两种缓解期望水平来操纵安慰剂的剂量。通过预测线索指定下一个要刺激的手指，也可以操纵期望的形式（暗示性或非暗示性）。主观报告和心理生理反应是评估安慰剂操作对随后疼痛处理的影响的关键指标。通过对 3 个结果指标（诱发电位、皮肤电反应、疼痛报告）的混合效应分析，以 3 个手指的预期顺序（即，操纵的期望水平）明确证明了剂量依赖性 PA。对缓解的期望越大，（1）随着刺激强度的增加，平均因变量斜率（响应灵敏度）的平均降低越大，（2）平均响应幅度的降低越大。出乎意料的是，非暗示性期望比暗示性期望导致稍大的 PA。该研究提供了明确的证据，表明 PA 可以以“剂量”依赖性的方式发生，这是由对缓解疼痛的期望水平介导的。
