Evidence for dopaminergic involvement in endogenous modulation of pain relief

  1. Simon Desch  Is a corresponding author
  2. Petra Schweinhardt
  3. Ben Seymour
  4. Herta Flor
  5. Susanne Becker  Is a corresponding author
  1. Heidelberg University, Germany
  2. University of Zurich, Switzerland
  3. John Radcliffe Hospital, United Kingdom
  4. Heinrich Heine University Düsseldorf, Germany

Abstract

Relief of ongoing pain is a potent motivator of behavior, directing actions to escape from or reduce potentially harmful stimuli. Whereas endogenous modulation of pain events is well characterized, relatively little is known about the modulation of pain relief and its corresponding neurochemical basis. Here we studied pain modulation during a probabilistic relief-seeking task (a 'wheel of fortune' gambling task), in which people actively or passively received reduction of a tonic thermal pain stimulus. We found that relief perception was enhanced by active decisions and unpredictability, and greater in high novelty-seeking trait individuals, consistent with a model in which relief is tuned by its informational content. We then probed the roles of dopaminergic and opioidergic signaling, both of which are implicated in relief processing, by embedding the task in a double-blinded cross-over design with administration of the dopamine precursor levodopa and the opioid receptor antagonist naltrexone. We found that levodopa enhanced each of these information-specific aspects of relief modulation but no significant effects of the opioidergic manipulation. These results show that dopaminergic signaling has a key role in modulating the perception of pain relief to optimize motivation and behavior.

Data availability

Behavioral and questionnaire data is available as csv file at the project's Open Science Framework page (osf.io/5xjt9).

The following data sets were generated

Article and author information

Author details

  1. Simon Desch

    Institute of Cognitive and Clinical Neuroscience, Heidelberg University, Mannheim, Germany
    For correspondence
    simon.desch@zi-mannheim.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5863-643X
  2. Petra Schweinhardt

    Department of Chiropractic Medicine, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Ben Seymour

    Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1724-5832
  4. Herta Flor

    Institute of Cognitive and Clinical Neuroscience, Heidelberg University, Mannheim, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Susanne Becker

    Heinrich Heine University Düsseldorf, Düsseldorf, Germany
    For correspondence
    sbecker@uni-duesseldorf.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5681-4084

Funding

Baden-Württemberg Stiftung (Postdoctoral Fellowship for Leading Early Career Researchers)

  • Susanne Becker

Universität Heidelberg (Olympia Morata Program)

  • Susanne Becker

Swiss National Science Foundation (PRIMA grant,PR00P1_179697/1)

  • Susanne Becker

Deutsche Forschungsgemeinschaft (Collaborative Research Centres,SFB1158 B03 and B07)

  • Herta Flor

Wellcome Trust (Senior Research Fellowship (214251/Z/18/Z))

  • Ben Seymour

Versus Arthritis (Research Award,21537)

  • Ben Seymour

Ministry of Science and ICT, South Korea (Technology Planning & Evaluation IITP grant,2019-0-01371)

  • Ben Seymour

Deutsche Forschungsgemeinschaft (Reinhart Koselleck Project,Fl 156/41-1)

  • Herta Flor

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Markus Ploner, Technische Universität München, Germany

Ethics

Human subjects: The study was approved by the Ethics Committee of the Medical Faculty Mannheim, Heidelberg University, (approval reference 2014-504N-MA) and written informed consent was obtained from all participants prior to participation according to the revised Declaration of Helsinki (World Medical Association, 2013).

Version history

  1. Received: June 27, 2022
  2. Preprint posted: July 13, 2022 (view preprint)
  3. Accepted: January 31, 2023
  4. Accepted Manuscript published: February 1, 2023 (version 1)
  5. Version of Record published: March 6, 2023 (version 2)

Copyright

© 2023, Desch et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Simon Desch
  2. Petra Schweinhardt
  3. Ben Seymour
  4. Herta Flor
  5. Susanne Becker
(2023)
Evidence for dopaminergic involvement in endogenous modulation of pain relief
eLife 12:e81436.
https://doi.org/10.7554/eLife.81436

Share this article

https://doi.org/10.7554/eLife.81436

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