Division for Psychology and Neuroscience, Department of Psychology and Behavioral Science, School of Business and Social Sciences, Aarhus University, Denmark.
Department of Psychology, University of Turin, Turin, Italy.
Pain. 2024 Feb 1;165(2):440-449. doi: 10.1097/j.pain.0000000000003035. Epub 2023 Sep 8.
The role of placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease (AD) is largely unknown, with only few studies in the area. Therefore, this study aims to investigate to which extent placebo analgesia and nocebo hyperalgesia effects are present in patients experiencing mild-to-moderate AD. Twenty-one patients with AD (test population) and 26 healthy participants (HP; design validation) were exposed to thermal pain stimulation on 3 test days: Lidocaine condition (open/hidden lidocaine administration), capsaicin condition (open/hidden capsaicin administration), and natural history (no treatment), in a randomized, within-subject design. Open lidocaine and open capsaicin were accompanied by verbal suggestions for pain relief and pain increase, respectively. Expected pain and actual pain intensity were measured on a numerical rating scale (0-10). Placebo and nocebo effects were calculated as pain differences in open-hidden lidocaine and capsaicin, respectively, controlled for no treatment. Healthy participants obtained a placebo effect ( P = 0.01) and a trend for a nocebo effect ( P = 0.07). Patients with AD did not obtain a placebo effect ( P = 0.44) nor a significant nocebo effect ( P = 0.86). Healthy participants expected lower and higher pain with open vs hidden lidocaine and capsaicin, respectively ( P < 0.001). The same expectation effects were seen in patients with AD (open vs hidden lidocaine, P = 0.008; open vs hidden capsaicin, P < 0.001). With a well-controlled experimental setting, this study suggests that patients with AD may not experience placebo analgesia effects. Nocebo hyperalgesia effects in patients with AD needs further research. These findings may have implications for the conduction of clinical trials and the treatment of patients with AD in clinical practice.
安慰剂镇痛和反安慰剂痛觉过敏在阿尔茨海默病（AD）患者中的作用在很大程度上是未知的，该领域仅有少数研究。因此，本研究旨在调查在轻度至中度 AD 患者中存在多大程度的安慰剂镇痛和反安慰剂痛觉过敏效应。21 名 AD 患者（试验人群）和 26 名健康参与者（HP；设计验证）在 3 个测试日接受热痛刺激：利多卡因条件（开放/隐藏利多卡因给药）、辣椒素条件（开放/隐藏辣椒素给药）和自然史（无治疗），采用随机、自身对照设计。开放利多卡因和开放辣椒素分别伴随着减轻疼痛和增加疼痛的口头建议。在数字评分量表（0-10）上测量预期疼痛和实际疼痛强度。安慰剂和反安慰剂效应分别计算为开放-隐藏利多卡因和辣椒素的疼痛差异，同时控制无治疗。健康参与者获得了安慰剂效应（P=0.01）和反安慰剂效应的趋势（P=0.07）。AD 患者未获得安慰剂效应（P=0.44）或显著的反安慰剂效应（P=0.86）。健康参与者预期开放时比隐藏时利多卡因和辣椒素的疼痛更低和更高（P<0.001）。AD 患者也观察到相同的期望效应（开放与隐藏利多卡因，P=0.008；开放与隐藏辣椒素，P<0.001）。在控制良好的实验环境下，本研究表明 AD 患者可能不会经历安慰剂镇痛效应。AD 患者的反安慰剂痛觉过敏效应需要进一步研究。这些发现可能对临床试验的进行和临床实践中 AD 患者的治疗有影响。
