Evidence for dopaminergic involvement in endogenous modulation of pain relief
- Heidelberg University, Germany
- University of Zurich, Switzerland
- John Radcliffe Hospital, United Kingdom
- 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).
Article and author information
Author details
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.
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).
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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Evidence for dopaminergic involvement in endogenous modulation of pain relief
eLife 12:e81436.
https://doi.org/10.7554/eLife.81436
