Role of Endogenous Opioid System in the Placebo Effect

描述(申请人提供)：疼痛治疗中的安慰剂效应可能导致增强疗效，从而混淆临床试验中对止痛药的评估。无论是从临床试验的混淆因素还是从治疗疼痛的可取现象的角度来看，安慰剂效应背后的生化机制都知之甚少。脑阿片系统参与了阿片类镇痛剂的作用，并在伤害性刺激的内源性调节中发挥作用。大量证据表明，内源性阿片系统也在止痛安慰剂效应中发挥作用。例如，许多(但不是全部)研究表明，安慰剂效应可能会被阿片类拮抗剂纳洛酮抑制。然而，没有直接证据表明在安慰剂反应中内源性阿片类药物会释放，也不知道大脑中哪些区域介导了阿片类药物介导的安慰剂效应。此外，纳洛酮不是阿片受体亚型选择性拮抗剂，因此，需要其他技术来更彻底地研究阿片系统在安慰剂反应中的作用。我们实验室最初开发的阿片受体的PET成像是检查大脑阿片系统在调节安慰剂效应中的作用的一种很好的方法。与信念、条件作用、期望和意义反应相关的行为和心理因素越来越多地被认识到是安慰剂反应的重要组成部分，但对它们与生物途径的关系的了解还不完整。在观察安慰剂状态下的安慰剂效应时，受试者之间存在很大的变异性，但目前还没有可靠的方法来预测哪些人会表现出安慰剂效应。阐明大脑阿片系统在安慰剂反应中的作用可以显著提高对这一重要的脑-脑相互作用的认识。因此，这项研究的具体目的是： 1)在表现出安慰剂反应的健康受试者中，比较在安慰剂条件下与非安慰剂条件下PET测量的区域MU阿片受体可用性。 2)确定区域MU阿片受体可获得性与安慰剂效应大小之间的关系。 3)确定在非疼痛条件下，安慰剂反应的大小和区域内阿片受体可获得性之间的关系。

DESCRIPTION (provided by applicant): The placebo effect in pain treatment can lead to enhanced efficacy and thereby confound the evaluation of analgesic medications in clinical trials. Whether viewed in the context of a confounder for clinical trials or a desirable phenomenon in the treatment of pain, the biochemical mechanisms underlying the placebo effect are poorly understood. The brain opioid system is involved in mediating the effects of opiate analgesics and plays a role in the endogenous modulation of noxious stimuli. Considerable evidence indicates that the endogenous opioid system also plays a role in the analgesia placebo effect. For example, many, but not all, studies have shown that the placebo effect may be inhibited by the opiate antagonist naloxone. Yet, there is no direct evidence that endogenous brain opioids are released during a placebo response, nor is it known which brain regions mediate opioid-mediated placebo effects. Furthermore, naloxone is not an opioid receptor subtype selective antagonist and therefore, other techniques are needed to examine more thoroughly the role of the opioid system in the placebo response. PET imaging of opioid receptors, originally developed by our laboratory, is an excellent method to examine the role of the brain opioid system in mediating the placebo effect. Behavioral and psychological factors that relate to belief, conditioning, expectancy and meaning response are increasingly realized to be important components of the placebo response, but knowledge of their relation to biological pathways is incomplete. There is large intersubject variability in observing a placebo effect during a placebo condition, but there is currently no reliable way of predicting which individuals will display a placebo effect. Elucidation of the role of the brain opioid system in the placebo response could significantly improve knowledge of this important mind-brain interaction. Accordingly, the specific aims of this study are to: 1) Compare regional mu opioid receptor availability measured by PET under a placebo condition vs. a non-placebo condition in healthy human subjects who demonstrate a placebo response. 2) Determine the relationships between regional mu opioid receptor availability and the magnitude of the placebo effect. 3) Identify relationships between the magnitude of the placebo response and regional mu opioid receptor availability in a non-painful condition.