Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Clinical Psychology, Department of Experimental Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Petra Schweinhardt
Integrative Spinal Research, Department of Chiropractic Medicine, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, Oxford, United Kingdom
Herta Flor
Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Clinical Psychology, Department of Experimental Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Integrative Spinal Research, Department of Chiropractic Medicine, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
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.
