Role of Endogenous Opioid System in the Placebo Effect

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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.