Pain processing in Parkinson’s disease: motivational-emotional vs. sensory-discriminative components

据报道，30%-85%的帕金森病（PD）患者存在疼痛。疼痛甚至被描述为帕金森病的早期症状，比运动症状早几年。标准的多巴胺能药物可以改善由于僵硬和运动波动引起的肌肉骨骼疼痛，但只有三分之一的PD患者报告这种药物对他们的疼痛有积极的影响。与此观察一致，抗帕金森药物似乎不会影响疼痛阈值。尽管PD患者已经描述了疼痛感知的改变，但PD患者疼痛的机制尚不清楚。我们的假设是PD的疼痛是由所谓的内侧疼痛系统的损伤引起的，与PD已知的神经解剖学损伤一致，导致疼痛处理的动机-情绪成分的改变，而不是感觉-区别性疼痛成分。以往关于帕金森病疼痛的研究主要集中在表征感觉-鉴别疼痛成分以及侧痛系统的反应，而在很大程度上忽略了动机-情绪疼痛反应。关注PD患者的感觉-区别性疼痛成分可能是由于缺乏关注情绪-动机疼痛加工的标准范式，而没有将其与感觉-区别性疼痛加工区分开来，至少部分原因是。这样一个范例已经被贝克尔博士发展和验证。在拟议的项目中，PD患者在多巴胺能药物的关闭和打开阶段以及年龄和性别匹配的健康对照组的疼痛感知将使用该范式进行评估。特别的重点将是分析疼痛处理的不同组成部分以及它们因PD而发生的变化。为了补充这些评估，将用脑磁图（MEG）研究与疼痛处理相关的大脑反应。我们期望内侧前额叶皮层内的伽马振荡编码疼痛刺激的情绪处理，而感觉运动区域内的α和伽马振荡编码实际疼痛强度。脑磁图的发现将有助于理解不同疼痛成分的机制，以及多巴胺对这些患者和健康对照者疼痛加工中枢机制的调节。本项目的结果将有助于(1)调和PD患者疼痛的不一致发现，(2)表征PD中不同疼痛成分的脑机制。有了这些知识，将有可能优化帕金森病的药物疼痛治疗，并开发非侵入性神经反馈方法来减少这些患者增加的疼痛感知。

Pain has been reported in 30%-85% of patients with Parkinson’s disease (PD). Pain has even been described as an early symptom of PD, preceding motor symptoms by a couple of years. Standard dopaminergic medication can improve musculoskeletal pain due to rigidity and motor fluctuation, but only a third of all PD patients reports a positive effect of this medication on their pain . In line with this observation, anti-Parkinsonian medication appears not to affect pain thresholds . Although altered pain perception has been described in PD, the mechanisms underlying pain in PD remain unclear. Our hypothesis is that pain in PD is caused by impairments in the so-called medial pain system, in line with known neuroanatomical impairments in PD, resulting in alterations of motivational-emotional components of pain processing as opposed to sensory-discriminative pain components.Previous studies on pain in PD have predominantly focused on characterizing sensory-discriminative pain components and therefore responses of the lateral pain system, largely ignoring motivational-emotional pain responses. The focus on sensory-discriminative pain components in PD patients has likely been caused, at least partially, by a lack of standard paradigms focusing on emotional-motivational pain processing and not distinguishing it from sensory-discriminative pain processing. Such a paradigm has been developed and validated by Dr. Becker. In the proposed project, pain perception of PD patients during OFF and ON phases of their dopaminergic medication and of age- and sex-matched healthy controls will be assessed using this paradigm. A particular focus will be on analyzing the different components of pain processing and their alteration due to PD. To complement these assessments, brain responses related to pain processing will be studied with magnetoencephalography (MEG). We expect gamma oscillations within the medial pre-frontal cortex to encode the emotional processing of painful stimuli, while alpha and gamma oscillations within the sensorimotor regions encode the actual pain intensity. The MEG findings should provide an understanding of the mechanisms of different pain components and their modulation by dopamine in the central mechanisms of pain processing in these patients and healthy controls. The results of this project should help (1) reconcile inconsistent findings on pain in PD patients and (2) characterizing brain mechanisms of different pain components in PD. With this knowledge, it will be possible to optimize pharmacological pain treatment in Parkinson’s disease and to develop non-invasive neurofeedback approaches to reduce increased pain perception in these patients.