Role of Endogenous Opioid System in the Placebo Effect

Summary

Principal Investigator: J C Campbell
Abstract: 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.
Funding Period: 2003-04-01 - 2009-12-31
more information: NIH RePORT

Top Publications

  1. pmc individual variation in sleep quality and duration is related to cerebral mu opioid receptor binding potential during tonic laboratory pain in healthy subjects
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
    Pain Med 14:1882-92. 2013
  2. ncbi How do changes in pain severity levels correspond to changes in health status and function in patients with painful diabetic peripheral neuropathy?
    Deborah L Hoffman
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, MD 21287, USA
    Pain 149:194-201. 2010
  3. pmc Self-reported sleep duration associated with distraction analgesia, hyperemia, and secondary hyperalgesia in the heat-capsaicin nociceptive model
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Eur J Pain 15:561-7. 2011
  4. pmc Catastrophizing delays the analgesic effect of distraction
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA
    Pain 149:202-7. 2010
  5. ncbi Changes in situation-specific pain catastrophizing precede changes in pain report during capsaicin pain: a cross-lagged panel analysis among healthy, pain-free participants
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Pain 11:876-84. 2010
  6. pmc Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Meyer 1 108, 600 N Wolfe Street, Baltimore, MD 21287, USA
    Pain 141:114-8. 2009

Scientific Experts

Detail Information

Publications6

  1. pmc individual variation in sleep quality and duration is related to cerebral mu opioid receptor binding potential during tonic laboratory pain in healthy subjects
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
    Pain Med 14:1882-92. 2013
    ..This preliminary, exploratory investigation sought to examine the relationship between sleep and functioning of the cerebral mu opioid system during the experience of pain in healthy participants...
  2. ncbi How do changes in pain severity levels correspond to changes in health status and function in patients with painful diabetic peripheral neuropathy?
    Deborah L Hoffman
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, MD 21287, USA
    Pain 149:194-201. 2010
    ..Changes in pain were also associated with changes in health status. Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinically important changes in function and health status...
  3. pmc Self-reported sleep duration associated with distraction analgesia, hyperemia, and secondary hyperalgesia in the heat-capsaicin nociceptive model
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA
    Eur J Pain 15:561-7. 2011
    ..The secondary hyperalgesia finding may implicate central involvement, whereas enhanced skin flare response suggests that sleep duration may also impact peripheral inflammatory mechanisms...
  4. pmc Catastrophizing delays the analgesic effect of distraction
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, USA
    Pain 149:202-7. 2010
    ..These results suggest that both distraction and catastrophizing have substantial effects on experimental pain in normal subjects and these variables interact as a function of time...
  5. ncbi Changes in situation-specific pain catastrophizing precede changes in pain report during capsaicin pain: a cross-lagged panel analysis among healthy, pain-free participants
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Pain 11:876-84. 2010
    ..Limitations of the present study and possible future research directions are discussed...
  6. pmc Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain
    Claudia M Campbell
    Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Meyer 1 108, 600 N Wolfe Street, Baltimore, MD 21287, USA
    Pain 141:114-8. 2009
    ..When combined, three of the five accounted for a surprisingly high 35% of the inter-individual variance in pain ratings. We conclude that SNPs of the GCH1 gene may profoundly affect the ratings of pain induced by capsaicin...