Necka Elizabeth A, Akintola Titilola, Yu Qingbao, Amir Carolyn M, Oretsky Olga, Atlas Lauren Y
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, Maryland 20892.
National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, Maryland 20892
J Neurosci. 2025 Aug 20;45(34):e0050252025. doi: 10.1523/JNEUROSCI.0050-25.2025.
Clinical trials, laboratory experiments, and neuroimaging studies provide converging evidence that pain is highly sensitive to expectations, whether based on the psychosocial context surrounding treatment (e.g., placebo analgesia) or transient cues that provide information about painful events (e.g., pain-predictive cues). We asked whether placebo analgesia and pain-predictive cues modulate pain through the same mechanisms or dissociable brain pathways. Forty healthy volunteers of both sexes rated pain in response to noxious heat during functional magnetic resonance imaging. We crossed pain-predictive cues, which induce expectations for high or low pain on a trial-by-trial basis, with administration of an inert placebo cream or a control cream. Behavioral analyses revealed a significant interaction, such that predictive cues had weaker effects on pain during placebo blocks than control blocks. This interaction was accompanied by interactions in the insula, pons, and other brain regions. We also observed distinct neural substrates when we compared pure cue effects with pure placebo effects, and only predictive cues modulated responses in nociceptive regions and the neurologic pain signature (Wager et al., 2013). The only regions that were influenced similarly by both types of expectations were the rostral anterior cingulate and dorsomedial prefrontal cortex. These results indicate that cue-based expectations about stimulus intensity and placebo-based expectations about treatment outcomes are distinct and that pain researchers should differentiate between sources of expectations. Furthermore, cue-based expectations were associated with more consistent effects than treatment-based expectations, suggesting that clinicians should be particularly mindful of how they present information about impending pain.
临床试验、实验室实验和神经影像学研究提供了越来越多的证据表明，疼痛对预期高度敏感，无论这种预期是基于治疗周围的社会心理背景（例如，安慰剂镇痛）还是基于提供有关疼痛事件信息的短暂线索（例如，疼痛预测线索）。我们询问安慰剂镇痛和疼痛预测线索是否通过相同的机制或可分离的脑通路来调节疼痛。40名健康的男女志愿者在功能磁共振成像期间对有害热刺激的疼痛进行评分。我们将逐次试验诱导对高或低疼痛预期的疼痛预测线索与给予惰性安慰剂乳膏或对照乳膏进行交叉。行为分析显示出显著的交互作用，即预测线索在安慰剂组对疼痛的影响比在对照组弱。这种交互作用伴随着脑岛、脑桥和其他脑区的交互作用。当我们将纯线索效应与纯安慰剂效应进行比较时，我们还观察到了不同的神经基质，并且只有预测线索调节了伤害性感受区域和神经病理性疼痛特征的反应（Wager等人，2013年）。两种类型的预期同样影响的唯一区域是喙前扣带回和背内侧前额叶皮层。这些结果表明，基于线索的关于刺激强度的预期和基于安慰剂的关于治疗结果的预期是不同的，并且疼痛研究人员应该区分预期的来源。此外，基于线索的预期比基于治疗的预期具有更一致的效果，这表明临床医生应该特别注意他们如何呈现关于即将到来的疼痛的信息。
