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Evidence for dopaminergic involvement in endogenous modulation of pain relief

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
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.7554/elife.81436

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Role:
Author
ORCID:
0000-0001-5863-643X
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Role:
Author
ORCID:
0000-0003-4837-6595
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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0003-1724-5832
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Role:
Author
ORCID:
0000-0003-4809-5398
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Role:
Author
ORCID:
0000-0002-5681-4084


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Funder identifier:
10.13039/501100001661
Grant:
Olympia Morata Program
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Funder identifier:
10.13039/100008316
Grant:
Postdoctoral Fellowship for Leading Early Career Researchers
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Funder identifier:
10.13039/501100001711
Grant:
PRIMA grant
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Funder identifier:
10.13039/100004440
Grant:
Senior Research Fellowship (214251/Z/18/Z)
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Funder identifier:
10.13039/501100012041
Grant:
Research Award 21537


Publisher:
eLife Sciences Publications
Journal:
eLife More from this journal
Volume:
12
Pages:
e81436
Article number:
e81436
Publication date:
2023-02-01
Acceptance date:
2023-01-31
DOI:
EISSN:
2050-084X
ISSN:
2050-084X


Language:
English
Keywords:
Pubs id:
1327862
Local pid:
pubs:1327862
Source identifiers:
W4318754360
Deposit date:
2026-05-01
ARK identifier:
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