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

据报道，帕金森氏病(PD)患者中有30%-85%出现疼痛。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效果。根据这一观察结果，抗帕金森症药物似乎不会影响痛觉阈值。尽管帕金森病患者的痛觉改变已被描述，但帕金森病患者疼痛的潜在机制仍不清楚。我们的假设是，帕金森病患者的疼痛是由所谓的中间疼痛系统的损害引起的，这与帕金森病患者已知的神经解剖学损害一致，导致疼痛处理的动机-情绪成分发生变化，而不是感觉辨别性疼痛成分。以前对帕金森病患者疼痛的研究主要集中在表征感觉辨别性疼痛成分，因此侧面疼痛系统的反应，很大程度上忽视了动机-情绪疼痛反应。帕金森病患者对感觉辨别性疼痛成分的关注可能至少部分是由于缺乏关注情绪动机疼痛处理的标准范式，而没有将其与感觉辨别性疼痛处理区分开来。贝克尔博士已经开发并验证了这种模式。在拟议的项目中，将使用该范式评估帕金森病患者在多巴胺能药物治疗的非阶段和非阶段以及年龄和性别匹配的健康对照组的痛觉。一个特别的重点将是分析疼痛处理的不同组成部分以及由于帕金森病引起的它们的改变。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。我们预计内侧前额叶皮质的伽马振荡编码疼痛刺激的情绪处理，而感觉运动区的阿尔法和伽马振荡编码实际的疼痛强度。脑磁图的发现应该有助于了解不同疼痛成分的机制，以及多巴胺在这些患者和健康对照组疼痛处理的中央机制中的调节作用。这个项目的结果应该有助于(1)协调关于帕金森病患者疼痛的不同发现，以及(2)表征帕金森病患者不同疼痛成分的脑机制。有了这些知识，就有可能优化帕金森氏病的药物疼痛治疗，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受。

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.