Endogenous modulation of pain relief: evidence for dopaminergic but not opioidergic involvement
Endogenous modulation of pain relief: evidence for dopaminergic but not opioidergic involvement
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DOI：
10.1101/2022.07.10.499477
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发表时间：
2022-07
期刊：
影响因子：
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通讯作者：
S. Desch;P. Schweinhardt;B. Seymour;Herta Flor;S. Becker
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文献类型：
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作者：
S. Desch;P. Schweinhardt;B. Seymour;Herta Flor;S. Becker
持续疼痛的缓解是行为的一个强有力的动机，指导行为逃避或减少潜在的有害刺激。虽然内源性调制的疼痛事件的特点，相对较少的是已知的调制疼痛缓解及其相应的神经化学基础。在这里，我们研究了疼痛调制过程中的概率寻求救济的任务（一个“幸运轮”赌博任务），其中人们主动或被动地收到减少的强直性热疼痛刺激。我们发现，救济知觉增强了积极的决定和不可预测性，更大的高新奇寻求特质的个人，符合一个模型，其中救济是由其信息内容调整。然后，我们探讨了多巴胺能和阿片样物质的信号传导，这两者都涉及救济处理的作用，通过嵌入的任务，在一个双盲交叉设计与管理的多巴胺前体左旋多巴和阿片受体拮抗剂纳洛酮。我们发现，左旋多巴，而不是纳洛酮，增强这些信息的具体方面的救济调制。这些结果表明，多巴胺能信号在调节疼痛缓解的感知以优化动机和行为方面具有关键作用。
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, but not naltrexone, enhanced each of these information-specific aspects of relief modulation. These results show that dopaminergic signaling has a key role in modulating the perception of pain relief to optimize motivation and behavior.