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Int Rev Neurobiol. 2018;139:129-157. doi: 10.1016/bs.irn.2018.07.022. Epub 2018 Aug 6.

Optimizing Placebo and Minimizing Nocebo to Reduce Pain, Catastrophizing, and Opioid Use: A Review of the Science and an Evidence-Informed Clinical Toolkit.

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School of Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Division of Pain Medicine, Psychiatry and Behavioral Sciences (by courtesy), Stanford University, Palo Alto, CA, United States. Electronic address:
Department of Pain Translational Symptom Science, School of Nursing, University of Maryland, Baltimore, MD, United States; Departments of Anesthesiology and Psychiatry, School of Medicine, University of Maryland, Baltimore, MD, United States; Center to Advance Chronic Pain Research, University of Maryland, Baltimore, MD, United States.


Pain, a noxious psychosensory experience, motivates escape behavior to assure protection and survival. Psychological factors alter the experience and trajectory of pain, as well as behavior and treatment response. In the context of pain, the placebo effect (expectation for pain relief) releases endogenous opioids and facilitates analgesia from exogenously administered opioids. Nocebo hyperalgesia (expectation for persistent or worsening pain) opposes endogenous opioid analgesia and patient engagement in prescription opioid tapering. Reductions in nocebo hyperalgesia and pain catastrophizing may enhance descending modulation of pain, mediate adaptive structural brain changes and promote patient engagement in opioid tapering. Interventions that minimize nocebo and optimize placebo may adaptively shape the central nervous system toward pain relief and potentially opioid reduction. Here we provide a critical description of catastrophizing and its impact on pain, placebo and nocebo effects. We also consider the importance of minimizing nocebo and optimizing placebo effects during prescription opioid tapering, and offer a clinical toolkit of resources to accomplish these goals clinically.


Catastrophizing; Chronic pain; Evidence-based; Expectations; Nocebo; Opioids; Pain; Patient-centered; Placebo; Treatment

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