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Research Article

Placebo analgesia and its opioidergic regulation suggest that empathy for pain is grounded in self pain

Markus Rütgen, Eva-Maria Seidel, Giorgia Silani, Igor Riečanský, Allan Hummer, Christian Windischberger, Predrag Petrovic, and Claus Lamm
PNAS October 13, 2015 112 (41) E5638-E5646; first published September 28, 2015; https://doi.org/10.1073/pnas.1511269112
Markus Rütgen
aSocial, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna 1010, Austria;
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Eva-Maria Seidel
aSocial, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna 1010, Austria;
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Giorgia Silani
bCognitive Neuroscience Sector, International School for Advanced Studies, Trieste 34136, Italy;
cDepartment of Applied Psychology: Health, Development, Enhancement and Intervention, Faculty of Psychology, University of Vienna, Vienna 1010, Austria;
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Igor Riečanský
aSocial, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna 1010, Austria;
dLaboratory of Cognitive Neuroscience, Institute of Normal and Pathological Physiology, Centre of Excellence for Examination of Regulatory Role of Nitric Oxide in Civilization diseases, Slovak Academy of Sciences, Bratislava 813 71, Slovakia;
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Allan Hummer
eMedical Research (MR) Center of Excellence, Medical University of Vienna, Vienna 1090, Austria;
fCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna 1090, Austria;
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Christian Windischberger
eMedical Research (MR) Center of Excellence, Medical University of Vienna, Vienna 1090, Austria;
fCenter for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna 1090, Austria;
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Predrag Petrovic
gCognitive Neurophysiology Research Group, Department of Clinical Neuroscience, Karolinska Institute, Stockholm 171 76, Sweden
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Claus Lamm
aSocial, Cognitive and Affective Neuroscience Unit, Department of Basic Psychological Research and Research Methods, Faculty of Psychology, University of Vienna, Vienna 1010, Austria;
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  • For correspondence: claus.lamm@univie.ac.at
  1. Edited by Naomi I. Eisenberger, University of California, Los Angeles, CA, and accepted by the Editorial Board August 25, 2015 (received for review June 16, 2015)

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Significance

Empathy is of major importance for everyday social interaction. Recent neuroscientific models suggest that pain empathy relies on the activation of brain areas that are also engaged during the first-hand experience of pain. These models rely on rather unspecific and correlational evidence. Here, we show that inducing pain analgesia also reduces pain empathy, and that this is associated with decreased activation of empathy-related brain areas. We then document that blocking placebo analgesia via an opioid antagonist also blocks placebo analgesia effects on pain empathy. This finding suggests that pain empathy is grounded in neural responses and neurotransmitter activity related to first-hand pain.

Abstract

Empathy for pain activates brain areas partially overlapping with those underpinning the first-hand experience of pain. It remains unclear, however, whether such shared activations imply that pain empathy engages similar neural functions as first-hand pain experiences. To overcome the limitations of previous neuroimaging research, we pursued a conceptually novel approach: we used the phenomenon of placebo analgesia to experimentally reduce the first-hand experience of pain, and assessed whether this results in a concomitant reduction of empathy for pain. We first carried out a functional MRI experiment (n = 102) that yielded results in the expected direction: participants experiencing placebo analgesia also reported decreased empathy for pain, and this was associated with reduced engagement of anterior insular and midcingulate cortex: that is, areas previously associated with shared activations in pain and empathy for pain. In a second step, we used a psychopharmacological manipulation (n = 50) to determine whether these effects can be blocked via an opioid antagonist. The administration of the opioid antagonist naltrexone blocked placebo analgesia and also resulted in a corresponding “normalization” of empathy for pain. Taken together, these findings suggest that pain empathy may be associated with neural responses and neurotransmitter activity engaged during first-hand pain, and thus might indeed be grounded in our own pain experiences.

  • pain
  • empathy
  • placebo
  • fMRI
  • psychopharmacology

Footnotes

  • ↵1To whom correspondence should be addressed. Email: claus.lamm{at}univie.ac.at.
  • Author contributions: M.R., E.-M.S., G.S., I.R., A.H., C.W., P.P., and C.L. designed research; M.R., E.-M.S., I.R., and A.H. performed research; M.R., E.-M.S., I.R., A.H., and C.W. analyzed data; and M.R., E.-M.S., G.S., I.R., A.H., C.W., P.P., and C.L. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission. N.I.E. is a guest editor invited by the Editorial Board.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1511269112/-/DCSupplemental.

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Empathy and placebo analgesia
Markus Rütgen, Eva-Maria Seidel, Giorgia Silani, Igor Riečanský, Allan Hummer, Christian Windischberger, Predrag Petrovic, Claus Lamm
Proceedings of the National Academy of Sciences Oct 2015, 112 (41) E5638-E5646; DOI: 10.1073/pnas.1511269112

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Empathy and placebo analgesia
Markus Rütgen, Eva-Maria Seidel, Giorgia Silani, Igor Riečanský, Allan Hummer, Christian Windischberger, Predrag Petrovic, Claus Lamm
Proceedings of the National Academy of Sciences Oct 2015, 112 (41) E5638-E5646; DOI: 10.1073/pnas.1511269112
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