From the Department of Neuroscience (Camerone, Piedimonte, Zamfira, Benedetti, Carlino), University of Turin Medical School, Turin; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Science (DINOGMI) (Camerone, Testa), University of Genoa, Genoa, Italy; Nuffield Department of Clinical Neurosciences (Wiech), University of Oxford, Oxford, United Kingdom; Department of Psychology and Behavioural Sciences, School of Business and Social Sciences (Vase), Aarhus University, Aarhus, Denmark; and Plateau Rosà Laboratories (Benedetti), Plateau Rosà, Italy/Switzerland.
Psychosom Med. 2021 Jan 1;83(1):43-50. doi: 10.1097/PSY.0000000000000882.
Expectations are known to be key determinants of placebo and nocebo phenomena. In previous studies, verbal suggestions to induce such expectations have mainly focused on the direction and magnitude of the effect, whereas little is known about the influence of temporal information.
Using an experimental placebo and nocebo design, we investigated whether information about the expected onset of a treatment effect modulates the start and time course of analgesic and hyperalgesic responses. Healthy volunteers (n = 166) in three placebo and three nocebo groups were informed that the application of an (inert) cream would reduce (placebo groups) or amplify pain (nocebo groups) after 5, 15, or 30 minutes. Two control groups were also included (natural history and no expectations). Participants' pain intensity rating of electrical stimuli administered before and 10, 20, and 35 minutes after cream application was obtained.
Mixed-method analysis of variance showed a significant interaction between group and time (F(12,262) = 18.172, p < .001, pη2 = 0.454), suggesting that pain variations differed across time points and between groups. Post hoc comparisons revealed that the placebo and nocebo groups began to show a significantly larger change in perceived pain intensity than the no-expectancy control group at the expected time point (p < .05) but not earlier (p > .05). Once triggered, the analgesic effect remained constant over the course of the experiment, whereas the hyperalgesic effect increased over time.
Our results indicate that temporal suggestions can shape expectancy-related treatment effects, which, if used systematically, could open up new ways to optimize treatment outcome.
预期被认为是安慰剂和反安慰剂现象的关键决定因素。在之前的研究中，主要通过言语暗示来诱导这种预期，侧重于效果的方向和幅度，而对于时间信息的影响知之甚少。
使用实验性安慰剂和反安慰剂设计，我们研究了关于治疗效果预期开始的信息是否会调节镇痛和痛觉过敏反应的开始和时间进程。在三个安慰剂组和三个反安慰剂组中，健康志愿者（n=166）被告知，应用（惰性）乳膏后，在 5、15 或 30 分钟后会减轻（安慰剂组）或加重疼痛（反安慰剂组）。还包括两个对照组（自然史和无预期）。在乳膏涂抹前和涂抹后 10、20 和 35 分钟，对参与者进行电刺激的疼痛强度评分。
混合方法方差分析显示，组间和时间间存在显著交互作用（F(12,262)=18.172，p<.001，pη2=0.454），表明疼痛变化在时间点和组间存在差异。事后比较表明，与无预期对照组相比，安慰剂组和反安慰剂组在预期时间点开始显示出更大的感知疼痛强度变化（p<.05），但更早时没有（p>.05）。一旦被触发，镇痛效果在实验过程中保持不变，而痛觉过敏效果随时间增加。
我们的结果表明，时间暗示可以塑造与预期相关的治疗效果，如果系统地使用，可能会开辟优化治疗效果的新途径。
