Role of Endogenous Opioid System in the Placebo Effect

描述（由申请人提供）：疼痛治疗中的安慰剂效应可导致疗效增强，从而混淆临床试验中镇痛药物的评估。无论是在临床试验的混杂因素背景下还是在疼痛治疗的理想现象中，安慰剂效应背后的生化机制都知之甚少。脑阿片系统参与阿片镇痛药物的介导作用，并在内源性有害刺激的调节中发挥作用。大量证据表明，内源性阿片系统也在镇痛安慰剂效应中起作用。例如，许多但不是全部的研究表明，安慰剂效应可能被阿片类拮抗剂纳洛酮所抑制。然而，没有直接证据表明内源性脑阿片样物质在安慰剂反应中释放，也不知道大脑的哪个区域介导阿片样物质介导的安慰剂效应。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检查阿片系统在安慰剂反应中的作用。阿片受体的PET成像，最初是由我们的实验室开发的，是一种很好的方法来检查大脑阿片系统在介导安慰剂效应中的作用。与信念、条件反射、期望和意义反应相关的行为和心理因素越来越被认为是安慰剂反应的重要组成部分，但它们与生物学途径的关系尚不完整。在安慰剂条件下，观察安慰剂效应在受试者之间存在很大的可变性，但目前还没有可靠的方法来预测哪些个体会表现出安慰剂效应。阐明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心脑相互作用的认识。因此，本研究的具体目的是：

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.