Thomaidou Mia A, Peerdeman Kaya J, Koppeschaar Melissa I, Evers Andrea W M, Veldhuijzen Dieuwke S
Health, Medical & Neuropsychology Unit, Leiden University, Leiden, Netherlands.
Leiden Institute for Brain and Cognition, Leiden, Netherlands.
Front Neurosci. 2021 Mar 24;15:652552. doi: 10.3389/fnins.2021.652552. eCollection 2021.
This comprehensive review summarizes and interprets the neurobiological correlates of nocebo hyperalgesia in healthy humans. Nocebo hyperalgesia refers to increased pain sensitivity resulting from negative experiences and is thought to be an important variable influencing the experience of pain in healthy and patient populations. The young nocebo field has employed various methods to unravel the complex neurobiology of this phenomenon and has yielded diverse results. To comprehend and utilize current knowledge, an up-to-date, complete review of this literature is necessary. PubMed and PsychInfo databases were searched to identify studies examining nocebo hyperalgesia while utilizing neurobiological measures. The final selection included 22 articles. Electrophysiological findings pointed toward the involvement of cognitive-affective processes, e.g., modulation of alpha and gamma oscillatory activity and P2 component. Findings were not consistent on whether anxiety-related biochemicals such as cortisol plays a role in nocebo hyperalgesia but showed an involvement of the cyclooxygenase-prostaglandin pathway, endogenous opioids, and dopamine. Structural and functional neuroimaging findings demonstrated that nocebo hyperalgesia amplified pain signals in the spinal cord and brain regions involved in sensory and cognitive-affective processing including the prefrontal cortex, insula, amygdala, and hippocampus. These findings are an important step toward identifying the neurobiological mechanisms through which nocebo effects may exacerbate pain. Results from the studies reviewed are discussed in relation to cognitive-affective and physiological processes involved in nocebo and pain. One major limitation arising from this review is the inconsistency in methods and results in the nocebo field. Yet, while current findings are diverse and lack replication, methodological differences are able to inform our understanding of the results. We provide insights into the complexities and involvement of neurobiological processes in nocebo hyperalgesia and call for more consistency and replication studies. By summarizing and interpreting the challenging and complex neurobiological nocebo studies this review contributes, not only to our understanding of the mechanisms through which nocebo effects exacerbate pain, but also to our understanding of current shortcomings in this field of neurobiological research.
这篇综述总结并解读了健康人群中反安慰剂高敏反应的神经生物学关联。反安慰剂高敏反应是指由负面经历导致的疼痛敏感性增加，被认为是影响健康人群和患者疼痛体验的一个重要变量。新兴的反安慰剂领域采用了多种方法来揭示这一现象复杂的神经生物学机制，并取得了多样的结果。为了理解和运用当前的知识，有必要对该文献进行最新、全面的综述。检索了PubMed和PsychInfo数据库，以识别使用神经生物学测量方法研究反安慰剂高敏反应的研究。最终筛选出22篇文章。电生理研究结果表明认知 - 情感过程参与其中，例如α和γ振荡活动以及P2成分的调制。关于皮质醇等与焦虑相关的生化物质是否在反安慰剂高敏反应中起作用，研究结果并不一致，但显示环氧合酶 - 前列腺素途径、内源性阿片类物质和多巴胺参与其中。结构和功能神经影像学研究结果表明，反安慰剂高敏反应增强了脊髓以及参与感觉和认知 - 情感处理的脑区（包括前额叶皮质、脑岛、杏仁核和海马体）中的疼痛信号。这些发现是朝着识别反安慰剂效应可能加剧疼痛的神经生物学机制迈出的重要一步。所综述研究的结果结合反安慰剂和疼痛相关的认知 - 情感及生理过程进行了讨论。本综述产生的一个主要局限性是反安慰剂领域在方法和结果上的不一致性。然而，尽管当前的研究结果多样且缺乏重复性，但方法上的差异有助于我们理解这些结果。我们深入探讨了反安慰剂高敏反应中神经生物学过程的复杂性和参与情况，并呼吁进行更多的一致性和重复性研究。通过总结和解读具有挑战性且复杂的反安慰剂神经生物学研究，本综述不仅有助于我们理解反安慰剂效应加剧疼痛的机制，也有助于我们理解该神经生物学研究领域当前的不足之处。
