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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Baseline reward circuitry activity and trait reward responsiveness predict expression of opioid analgesia in healthy subjects
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Baseline reward circuitry activity and trait reward responsiveness predict expression of opioid analgesia in healthy subjects

机译：基线奖励回路活动和特质奖励响应性可预测健康受试者中阿片类镇痛的表达

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摘要

Variability in opioid analgesia has been attributed to many factors. For example, genetic variability of the μ-opioid receptor (MOR)-encoding gene introduces variability in MOR function and endogenous opioid neurotransmission. Emerging evidence suggests that personality trait related to the experience of reward is linked to endogenous opioid neurotransmission. We hypothesized that opi-oid-induced behavioral analgesia would be predicted by the trait reward responsiveness (RWR) and the response of the brain reward circuitry to noxious stimuli at baseline before opioid administration. In healthy volunteers using functional magnetic resonance imaging and the μ-opioid agonist remifentanil, we found that the magnitude of behavioral opioid analgesia is positively correlated with the trait RWR and predicted by the neuronal response to painful noxious stimuli before infusion in key structures of the reward circuitry, such as the orbitofrontal cortex, nucleus accumbens, and the ventral teg-mental area. These findings highlight the role of the brain reward circuitry in the expression of behavioral opioid analgesia. We also show a positive correlation between behavioral opioid analgesia and opioid-induced suppression of neuronal responses to noxious stimuli in key structures of the descending pain modulatory system (amygdala, periaqueductal gray, and rostral-ventromedial medulla), as well as the hippocampus. Further, these activity changes were predicted by the preinfusion period neuronal response to noxious stimuli within the ventral tegmentum. These results support the notion of future imaging-based subject-stratification paradigms that can guide therapeutic decisions.
机译：阿片类镇痛的变异性归因于许多因素。例如，μ阿片受体（MOR）编码基因的遗传变异性会导致MOR功能和内源性阿片类神经传递的变异性。新兴证据表明，与奖赏经历相关的人格特质与内源性阿片样物质神经传递有关。我们假设阿片类药物诱导的行为镇痛将由阿片类药物给药前的特质奖励响应性（RWR）和大脑奖励电路对有害刺激的响应来预测。在使用功能磁共振成像和μ阿片类激动剂瑞芬太尼的健康志愿者中，我们发现行为类阿片镇痛的程度与RWR特质呈正相关，并由输注奖励关键结构之前对伤害性伤害性刺激的神经元反应预测。电路，例如眶额叶皮层，伏隔核和腹侧被盖区。这些发现突出了大脑奖励电路在行为阿片类镇痛表达中的作用。我们还显示出行为阿片类药物的镇痛作用与阿片类药物诱导的对痛性下降调节系统的主要结构（杏仁核，导水管周围的灰质和延髓侧腹膜延髓）以及海马中有害刺激的神经元反应的抑制之间存在正相关。此外，这些活性的变化是通过输注前期对腹侧被膜内有害刺激的神经元反应来预测的。这些结果支持了可以指导治疗决策的未来基于影像的受试者分层范例的概念。

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    Vishvarani Wanigasekera; Michael C. Lee; Richard Rogers; Yazhuo Kong; Siri Leknes; Jesper Andersson; Irene Tracey;

  • 作者单位

    Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, Nuffield Division of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headington, Oxford 0X3 9DU, United Kingdom;

    Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, Nuffield Division of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headington, Oxford 0X3 9DU, United Kingdom,Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge CB2 1TN, United Kingdom;

    Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, Nuffield Division of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headington, Oxford 0X3 9DU, United Kingdom;

    Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, Nuffield Division of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headington, Oxford 0X3 9DU, United Kingdom;

    Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, Nuffield Division of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headington, Oxford 0X3 9DU, United Kingdom,Department of Psychology, University of Oslo, 0317 Oslo, Norway;

    Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, Nuffield Division of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headington, Oxford 0X3 9DU, United Kingdom;

    Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, Nuffield Division of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headington, Oxford 0X3 9DU, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    functional MRI; functional imaging; endophenotype;

    机译：功能性MRI;功能成像;内表型;

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