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Specifying the non-specific factors underlying opioid analgesia: expectancy, attention, and affect

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Abstract

Rationale

Psychological processes such as expectancy, attention, and affect directly influence clinical outcomes. These factors are grouped together as “nonspecific” factors, or placebo effects, in the medical literature, and their individual contributions are rarely considered. The pain-reducing effects of analgesic treatments may reflect changes in these psychological factors, rather than pure drug effects on pain. Furthermore, drug effects may not be isolated by drug vs. placebo comparisons if drugs interact with relevant psychological processes.

Objectives

We sought to determine whether the analgesic effects of opioid and placebo treatment are mediated by changes in attention, expectancy, or affect.

Methods

We crossed intravenous administration of a potent opioid analgesic, remifentanil, with information about drug delivery (treatment expectancy or placebo) using a balanced placebo design. We measured drug and treatment expectancy effects on pain, attention, and responses to emotional images. We also examined interactions with cue-based expectations about noxious stimulation or stimulus expectancy.

Results

Pain was additively influenced by treatment expectancy, stimulus expectancy, and drug concentration. Attention performance showed a small but significant interaction between drug and treatment expectancy. Finally, remifentanil enhanced responses to both positive and negative emotional images.

Conclusions

The pain-relieving effects of opioid drugs are unlikely to be mediated by changes in threat or affective processing. Standard open-label opioid administration influences multiple clinically relevant cognitive and emotional processes. Psychological factors can combine with drug effects to influence multiple outcomes in distinct ways. The influence of specific psychological factors should be considered when developing and testing pharmacological treatments.

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Acknowledgments

The authors would like to thank Namema Amendi and Steven Dashnaw for helpful assistance in data collection, and Stephen Shafer for assistance with the pharmacokinetic model of remifentanil. This work was funded by the NIH (NIMH RO1MH076136 and NIDA RO1DA027794, awarded to T.D.W.). The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Psychology, New York University, 6 Washington Place, New York, NY, 10003, USA

    Lauren Y. Atlas

  2. Department of Psychology, University of Wisconsin—Madison, Madison, WI, USA

    Joseph Wielgosz

  3. Department of Anesthesiology, Columbia University, New York, NY, USA

    Robert A. Whittington

  4. Department of Psychology and Neuroscience, University of Colorado-Boulder, Boulder, CO, USA

    Tor D. Wager

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  1. Lauren Y. Atlas
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  2. Joseph Wielgosz
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  3. Robert A. Whittington
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  4. Tor D. Wager
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Correspondence to Lauren Y. Atlas.

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Atlas, L.Y., Wielgosz, J., Whittington, R.A. et al. Specifying the non-specific factors underlying opioid analgesia: expectancy, attention, and affect. Psychopharmacology 231, 813–823 (2014). https://doi.org/10.1007/s00213-013-3296-1

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  • DOI: https://doi.org/10.1007/s00213-013-3296-1

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