Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: An fMRI study in healthy placebo responders and nonresponders

Elsenbruch, Sigrid; Kotsis, Vassilios; Benson, Sven; Rosenberger, Christina; Reidick, Daniel; Schedlowski, Manfred; Bingel, Ulrike; Theysohn, Nina; Forsting, Michael; Gizewski, Elke R.

doi:10.1016/j.pain.2011.10.036

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Volume 153, Issue 2 , Pages 382-390, February 2012

Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: An fMRI study in healthy placebo responders and nonresponders

Sigrid Elsenbruch
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
- Corresponding author. Address: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany. Tel.: +49 201 723 4502; fax: +49 201 723 5948.
Vassilios Kotsis
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Sven Benson
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Christina Rosenberger
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
- Institute of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Daniel Reidick
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Manfred Schedlowski
- Institute of Medical Psychology and Behavioral Immunobiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Ulrike Bingel
- Neuroimage Nord, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Nina Theysohn
- Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Michael Forsting
- Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Elke R. Gizewski
- Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
- Department of Neuroradiology, Centre for Radiology, University Clinic of Gießen and Marburg, Justus-Liebig-University Gießen, Gießen, Germany

Received 4 August 2011; received in revised form 12 October 2011; accepted 27 October 2011. published online 05 December 2011.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Summary

In this placebo analgesia study, the expectation of pain relief reduced perceived painfulness of visceral stimuli, which was associated with activity changes in thalamus, and prefrontal and somatosensory cortices.

Abstract

This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N=36 healthy subjects, the blood oxygen level–dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0%>100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain.