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.
Elife. 2023 Feb 1;12:e81436. doi: 10.7554/eLife.81436.
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.
持续疼痛的缓解是行为的有力动机，引导人们逃避或减轻潜在的有害刺激。尽管内源性疼痛事件的调节已得到很好的描述，但对于疼痛缓解的调节及其相应的神经化学基础知之甚少。在这里，我们在一个概率性缓解寻求任务（“幸运轮”赌博任务）中研究了疼痛调节，在该任务中，人们主动或被动地减少了持续的热痛刺激。我们发现，缓解感知会因主动决策和不可预测性而增强，而且在高新奇寻求特质个体中更为明显，这与一种模型一致，即缓解是通过其信息内容来调节的。然后，我们通过将任务嵌入到双盲交叉设计中，用多巴胺前体左旋多巴和阿片受体拮抗剂纳曲酮进行干预，探究了多巴胺能和阿片能信号在缓解处理中的作用。我们发现，左旋多巴增强了缓解调节的这些信息特异性方面中的每一个方面，但阿片能操作没有显著影响。这些结果表明，多巴胺能信号在调节疼痛缓解的感知方面起着关键作用，以优化动机和行为。
