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

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


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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Catastrophization* / drug therapy
  • Catastrophization* / psychology
  • Humans
  • Hyperalgesia / drug therapy
  • Hyperalgesia / psychology
  • Nocebo Effect*
  • Pain / drug therapy*
  • Pain / psychology*
  • Pain Management
  • Placebo Effect*


  • Analgesics, Opioid