Psychobiological mechanisms of impaired reward processing in chronic pain

慢性疼痛是一个重大问题，造成巨大的个人痛苦和巨大的社会经济代价。虽然疼痛研究在过去的几十年里取得了很大的进步，但有效的治疗选择仍然有限。这种缺乏可能是由于疼痛研究主要集中在伤害性感觉的分子和神经机制(即，对损害或威胁损害组织的刺激进行编码的神经过程)，而忽视了疼痛时的多方面体验。最近，情绪-动机加工在疼痛中的潜在病因和致病作用已被强调，超越了伤害性加工。在慢性疼痛中，从伤害性大脑回路到情感动机大脑回路的转变反映了一种负享乐主义的转变。这样的转变被认为会导致奖励性刺激，因为它们被认为回报较低。然而，目前可用的数据还不能得出结论，慢性疼痛患者的奖励处理是否真的发生了变化，这种变化的心理生物学机制仍然难以捉摸。提供了一个概念性机制导向的框架，本项目旨在描述慢性疼痛患者在奖赏加工过程中的变化以及相应的神经关联。为此，50名慢性背痛患者和50名健康对照将分别参加一次功能磁共振成像(FMRI)和一次实验室会议。在功能磁共振成像课程中，动机和享乐体验以及与金钱得失相关的相应神经关联作为强大的二级奖励和惩罚，以及作为厌恶刺激的原型的急性疼痛刺激及其作为奖励事件的避免，将被调查，以及当两者同时存在时，金钱奖励与痛苦避免的权衡。实验室会议包括对与食物有关的刺激的动机和享乐体验作为潜在和显性的主要奖励的评估，以及全面的临床评估。对行为和成像数据的分析旨在测试与行为改变相关的大脑回路中具体提出的改变，以填补现有文献中的空白。选定的实验范式允许对奖赏刺激处理过程中的变化进行具体评估和区分，这些变化被认为是疼痛慢性化加剧的基础，包括情感共病，因此从理论上和临床角度都很重要。预期结果将为今后的工作提供必要的基础，为在慢性疼痛的基于机制的干预治疗中利用与奖励处理相关的机制铺平道路，这些机制在慢性疼痛中功能失调。

Chronic pain is a major problem causing immense personal suffering and enormous socioeconomic costs. Although pain research has made great progress in the last decades, effective therapy options are still limited. This lack is probably caused by pain research largely focusing on molecular and neuronal mechanisms of nociception (i.e. the neural process of encoding of stimuli that damage or threaten to damage tissues), neglecting multifaceted experiences when being in pain. Recently, the potential etiological and pathogenetic role of emotional-motivational processing when being in pain, going beyond nociceptive processing, has been emphasized. A negative hedonic shift that is mirrored in a shift from nociceptive to emotional-motivational brain circuits has been described in chronic pain. Such a shift is assumed to cause rewarding stimuli as being perceived as less rewarding. However, the currently available data does not allow a conclusion on whether reward processing is truly altered in chronic pain patients and the psychobiological mechanisms of such a shift remain elusive. Providing a conceptual mechanism-oriented framework, the present project aims to characterize alterations in the processing of reward and corresponding neural correlates in patients with chronic pain. For this purpose, 50 patients with chronic back pain and 50 healthy controls will participate each in one functional magnetic resonance imaging (fMRI) and one laboratory session. In the fMRI session, motivation and hedonic experience and corresponding neural correlates related to monetary wins and losses as powerful secondary rewards and punishment and acute pain stimuli as a prototype of aversive stimuli and their avoidance as a rewarding event will be investigated as well as weighting of monetary rewards against avoidance of pain, when both are present concurrently. The laboratory session comprises an assessment of the motivation and hedonic experience of food-related stimuli as potent primary rewards at implicit and explicit levels and a comprehensive clinical assessment. Analysis of behavioral together with imaging data is aimed at testing specifically proposed alterations in brain circuits related to behavioral alterations to close a gap in the available literature. The chosen experimental paradigms allow a specific evaluation and differentiation of alterations in the processing of rewarding stimuli, which have been proposed as underlying the exacerbation of the chronification of pain, including affective comorbidities, thus being important from a theoretical, but also clinical perspective. Expected results will provide a necessary basis for future work, paving the way for exploiting mechanisms related to reward processing that are dysfunctional in chronic pain in mechanism-based interventions for the treatment of chronic pain.