PDF(Pubmed)
Abstract：
Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study (N = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes.
摘要：
疼痛的药物治疗通常不会超过安慰剂，并且需要更好地了解安慰剂机制以改善治疗开发和临床实践。在一项具有预注册分析的大规模功能磁共振成像研究(N=392)中，我们测试了安慰剂镇痛治疗是否能调节伤害性过程，以及其效果是否从条件性疼痛模式推广到非条件性疼痛模式。安慰剂治疗在条件性热痛中引起强烈的镇痛作用，这种疼痛一般为非条件性机械性疼痛。然而,安慰剂并没有降低与伤害性疼痛相关的大脑功能磁共振成像活性，包括神经疼痛信号（NPS）和脊髓丘脑通路区域，在贝叶斯因子分析中强烈支持零效应。此外,令人惊讶的是,安慰剂在非条件性机械性疼痛的一些脊髓丘脑区域增加了活动。相比之下,安慰剂降低了与更高水平的疼痛相关的神经标记的活性，与刺激强度无关的疼痛信号(SIPS)，以及与动机和价值相关的大脑区域的活动受到影响，在两种疼痛模式中。行为镇痛的个体差异与两种方式的神经变化有关。我们的结果表明，认知和情感过程主要驱动安慰剂镇痛，并显示了神经标记物用于将治疗对伤害感受的影响与对评估过程的影响分开的潜力。
