Department of Neurology, Center of Translational Neuro- and Behavioural Sciences, University Medicine Essen, University Duisburg-Essen, Essen, Germany.
Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Eur J Neurosci. 2022 Jul;56(2):3967-3978. doi: 10.1111/ejn.15687. Epub 2022 Jun 16.
The neural mechanisms underlying placebo analgesia have attracted considerable attention over the recent years. In contrast, little is known about the neural underpinnings of a nocebo-induced increase in pain. We previously showed that nocebo-induced hyperalgesia is accompanied by increased activity in the hippocampus that scaled with the perceived level of anxiety. As a key node of the neural circuitry of perceived threat and fear, the hippocampus has recently been proposed to coordinate defensive behaviour in a context-dependent manner. Such a role requires close interactions with other regions involved in the detection of and responses to threat. Here, we investigated the functional connectivity of the hippocampus during nocebo-induced hyperalgesia. Our results show an increase in functional connectivity between hippocampus and brain regions implicated in the processing of sensory-discriminative aspects of pain (posterior insula and primary somatosensory/motor cortex) as well as the periaqueductal grey. This nocebo-induced increase in connectivity scaled with an individual's increase in anxiety. Moreover, hippocampus connectivity with the amygdala was negatively correlated with the pain intensity reported during nocebo hyperalgesia relative to the placebo condition. Our findings suggest that the hippocampus links nocebo-induced anxiety to a heightened responsiveness to nociceptive input through changes in its crosstalk with pain-modulatory brain areas.
近年来，安慰剂镇痛的神经机制引起了广泛关注。相比之下，人们对痛觉过敏的神经基础知之甚少。我们之前的研究表明，痛觉过敏是由海马体活动增加引起的，而这种增加与感知到的焦虑程度成正比。作为感知威胁和恐惧的神经回路的关键节点，海马体最近被提出以情境依赖的方式协调防御行为。这种作用需要与其他涉及威胁检测和反应的区域密切相互作用。在这里，我们研究了痛觉过敏期间海马体的功能连接。我们的研究结果表明，在痛觉过敏期间，海马体与大脑中与疼痛的感觉辨别方面的处理有关的区域（后岛叶和初级体感/运动皮层）以及导水管周围灰质之间的功能连接增加。这种与痛觉过敏相关的连接增加与个体的焦虑增加成正比。此外，海马体与杏仁核的连接与痛觉过敏期间报告的疼痛强度呈负相关，与安慰剂条件相比。我们的研究结果表明，海马体通过改变与疼痛调节脑区的串扰，将痛觉过敏引起的焦虑与对伤害性输入的反应性增强联系起来。
