帕金森病疼痛机制研究进展

帕金森病是中老年人群常见的神经变性病,临床表现主要包括运动症状和非运动症状,疼痛是常见的非运动症状,因影响患者生活质量而倍受关注。然而目前关于帕金森病疼痛的发病机制仍不明确,尚待进一步研究。本文拟就可能的帕金森病疼痛发病机制进行阐述。     

帕金森病伴疼痛发病机制的研究进展

帕金森病(PD)是中老年人常见的中枢神经系统退行性疾病,疼痛是PD较常见的非运动症状,其发病机制尚未完全阐明,目前认为PD伴疼痛与多个因素有关,文中就PD合并疼痛的发病机制研究进展作一综述。     

蓝斑参与刺激下丘脑视上核引起的加强电针镇痛

本工作应用核团灌流液的放射免疫测定（ＲＩＡ），高压液相（ＨＰＬＣ）以及核团内注射拮抗剂，观察了蓝斑（ＬＣ）在刺激下丘脑视上核（ＳＯＮ０引起的加强电针（ＥＡ）镇痛效应中的作用，结果表明，化学检测ＳＯＮ后电针期间和停针后３０，６０ｍｉｎ蓝斑灌流液内ＯＴ的含量明显升高，刺激ＳＯＮ后电针期间灌流液内精氨酸加压素（ＡＶＰ）含量明显升高，停针后ＡＶＰ的含量虽高于对照组及注射前的水平，但无统计学意义，ＬＣ灌流夜     

通过国王帕金森病疼痛量表分析帕金森病患者疼痛的临床特点

目的应用国王帕金森病疼痛量表(KPPS)对帕金森病(PD)患者的疼痛症状进行评估和分类,分析其临床特点。方法收集200例在南昌大学第一附属医院就诊的原发性PD患者的临床资料。运用KPPS量表评估患者的疼痛症状,运用统一PD评分量表第三部分(UPDRSⅢ)、Hoehn-Yahr分级(H-Y)、MMSE、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)、日常生活能力量表(ADL)、匹兹堡睡眠质量指数(PSQI)分别评估患者的运动功能、症状的严重程度、认知功能、焦虑状况、抑郁状况、生活自理能力及睡眠情况。将患者分为PD伴疼痛组和不伴疼痛组,对两组进行分析比较,并且寻找PD伴疼痛的相关影响因素。结果 PD伴发疼痛的发生率为44.5%,平均KPPS评分为(41.2±26.8)分。患者疼痛部位多为下肢(60.7%)、上肢(22.5%)及腰部(21.3%),其中24例(27%)患者伴两种及两种以上部位疼痛;疼痛类型多为骨骼肌疼痛(61.8%)和肌张力障碍性疼痛(27%),其中伴多种类型疼痛患者17例(19.1%)。PD伴疼痛组与PD不伴疼痛组相比,其病程更长(P=0.022)、左旋多巴等效...     

帕金森病康复治疗及其作用机制研究进展

帕金森病是渐进性黑质致密部多巴胺能神经元退行性变导致的疾病,康复治疗可以延缓病情进展,改善运动症状和非运动症状,提高患者日常生活活动能力。康复训练改善帕金森病症状的机制复杂,涉及多种分子学机制,本文系统阐述康复训练对帕金森病症状的改善作用,以及神经递质、营养因子、突触可塑性和免疫系统等方面的分子学机制。     

帕金森病运动并发症发生机制的研究进展

帕金森病是临床常见的中枢神经系统变性疾病,拟多巴胺类药物仍是其主要治疗手段.帕金森病患者长期接受多巴胺替代治疗后,可出现运动并发症,发生机制目前尚未完全阐明,而且对有些运动并发症仍缺乏有效的治疗方法,给帕金森病的治疗带来了困难和挑战.近年来,国内外学者对帕金森运动并发症的发生机制进行了广泛的研究,取得了显著进展,本文拟从左旋多巴药代动力学及药效学、神经生化学等角度阐述导致运动并发症的相关机制,以期为后续帕金森运动并发症的机制及治疗相关研究提供新视野.     

帕金森病相关疼痛

疼痛是帕金森病最常见且最棘手的非运动症状,其患病率高达40%以上。PD的疼痛可分为许多不同的亚型,包括肌肉骨骼、肌张力障碍、根性/神经性痛、中枢性疼痛以及静坐不能等。PD相关疼痛尚无统一的评估标准,难以开展个性化治疗,但左旋多巴能改善多数PD相关疼痛患者。其发病可能与CNS的外侧和内侧感觉系统以及外周神经病变有关,但具体机制尚未明确。     

帕金森病患者疼痛与睡眠障碍的相关性

目的 探讨伴疼痛的帕金森病(PD)患者的临床特征,并分析PD患者疼痛与睡眠障碍的相关性.方法 118例原发性PD患者分为伴疼痛组与不伴疼痛组,调查他们的一般特征,使用VAS评价患者的疼痛程度,使用UPDRSⅡ、UPDRSⅢ、H-Y分期、HAMD-17、HAMA量表、PDQ-8分别评价患者的运动症状、疾病严重程度、神经精神症状、生活质量.使用PDSS-2、ESS和PSG评价患者的睡眠情况.并对两组人群进行比较.结果 伴疼痛组病程长,UPDRS得分、H-Y分期、左旋多巴等效剂量、HAMD、HAMD、PDSS-2、PDQ-8得分均高于不伴疼痛组(P＜0.05).HAMD和PDSS-2评分与是PD患者疼痛的独立危险因素.VAS评分与PDSS-2评分有相关性,伴疼痛的PD患者与不伴疼痛患者相比,PSG主要表现为入睡潜伏期延长,睡眠效率下降,N1百分比增多、觉醒次数增多.结论 PD患者中,抑郁、睡眠障碍是疼痛的影响因素;PD疼痛与睡眠障碍有相关性;伴疼痛的PD患者夜间睡眠更差.     

帕金森病疼痛与非疼痛患者运动症状及运动并发症的比较研究

目的 比较帕金森病(PD)疼痛与非疼痛患者运动症状及运动并发症的差异,分析其与PD疼痛的关系.方法 收集自2019年1月至2019年12月就诊于山西医科大学第一医院的47例原发性PD患者,另招募20名健康对照者,根据国王帕金森病疼痛量表(KPPS)将PD患者分为疼痛组26例和非疼痛组21例.利用帕金森动力图系统评价各组...     

帕金森病相关骨骼肌肉疼痛的中枢机制及治疗研究现状

<正>帕金森病(Parkinson’s disease,PD)是伴有多种运动及非运动症状的神经变性疾病。近些年来非运动症状引起越来越多的重视,包括疼痛、情绪、嗅觉、认知、便秘等,其中疼痛一直有着高伴发率,并逐渐引起学界的重视。其实早在1817年詹姆斯帕金森就曾在专论里写到,疼痛可以是帕金森病疾病损害的早期警示征~([1])。疼痛定义是指一种与组织损伤或潜在组织损伤相关的感觉、情感、认知和社会维度的痛     

帕金森病相关外泌体研究进展

帕金森病（Parkinson disease, PD）是一种神经变性疾病,具有不可逆性、高发病率和高致 残率的特点,早期识别和干预对改善PD 意义重大。然而,目前临床上对PD 的诊断缺乏客观的实验室 检测指标,药物疗法对早期疾病修饰的证据尚不充分。外泌体是细胞产生、释放到胞外环境的囊泡,内 含丰富的生物活性分子。中枢神经系统起源的外泌体,其中PD标志性蛋白质,如α-突触核蛋白、DJ-1 和RNA 分子水平的变化反映了机体病理生理状态的改变,是筛选疾病诊断、鉴别诊断、分期、预后等标 志物的重要来源。间充质干细胞来源的外泌体具有与母细胞类似的组织修复、神经保护效应,而一些 活性分子（如过氧化物酶、多巴胺、小干扰RNAs等）也可以外泌体为载体靶向运输到脑组织,针对PD 不 同的致病通路发挥作用。现综述外泌体在PD 发生发展、诊断和治疗中的研究进展,探讨当前所面临的 问题和未来可能的研究方向。     

帕金森病多巴胺失调综合征的研究进展

多巴胺失调综合征（DDS）是一种由于对多巴胺能药物成瘾而产生一系列精神行为异常表 现的临床综合征，最常见于使用多巴胺能药物替代治疗的帕金森病患者。现从危险因素、发病机制、临 床表现、诊断评估、治疗及预后等多个方面阐述帕金森病DDS 的研究进展。     

帕金森病基因型和表型研究进展

帕金森病(PD)是常见的神经系统变性疾病之一,国外报道65岁以上的患病率达到2%,国内60岁以上为1%以上.目前认为PD的发病机制可能是环境因素和遗传因素共同作用的结果.近几年有关PD的基因发现,为研究PD发病的遗传基础燃起了新的希望.本文概括了目前与PD相关的基因研究状况以及和这些基因改变相关的PD病人临床特征.     

Activation of locus coeruleus by prefrontal cortex is mediated by excitatory amino acid inputs

We examined the role of excitatory amino acids (EAAs) in activation of noradrenergic locus coeruleus (LC) neurons evoked by electrical stimulation of the medial prefrontal cortex (mPFC) in halothane-anesthetized rats. Microinfusion of the specific N-methyl-

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-aspartate antagonist 2-amino-5-phosphonopentanoic acid (AP5, 50 or 100 μM) into the LC significantly suppressed LC responses evoked by mPFC stimulation. Microinfusion of the selective non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 25 or 50 μM) also significantly reduced evoked LC responses. Simultaneous microinfusion of both AP5 and CNQX considerably increased the proportion of LC neurons which exhibited complete suppression of evoked responses (81%), compared to either AP5 or CNQX alone (50% each). These results indicate that LC activation by mPFC stimulation is mediated by both NMDA- and non-NMDA-type EAA channels.     

Functional consequences of locus coeruleus degeneration in Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients, and its prevalence is expected to soar in coming decades. Neuropathologically, AD is characterized by beta-amyloid-containing plaques, tau-containing neurofibrillary tangles, and cholinergic neuronal loss. In addition to the hallmark of memory loss, the disease is associated with other neuropsychiatric and behavioral abnormalities, including psychosis, aggression, and depression. Although cholinergic cell loss is clearly an important attribute of the pathological process, another well-described yet underappreciated early feature of AD pathogenesis is degeneration of the locus coeruleus (LC), which serves as the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The purpose of this review is to explore the extent to which LC loss contributes to AD neuropathology and cognitive deficits.     

帕金森病相关睡眠障碍的研究进展

帕金森病是指以运动迟缓为主要表现的神经系统退行性疾病,至少存在静止性震颤或强直两主征中一项。除上述典型的运动症状外,帕金森病患者还存在睡眠障碍、自主神经功能障碍、嗅觉减退、精神障碍等非运动症状。某项针对391例帕金森病患者的研究表明［1］,在影响其生活质量的因素中,抑郁、睡眠障碍、疲劳3项共占61．7％,由此可见,非运动症状已成为影响帕金森病患者生活质量的主要原因。在非运动症状中,睡眠障碍会引起抑郁、焦虑等精神障碍,甚至导致认知障碍,严重影响患者的生活质量。现对帕金森病相关睡眠障碍的研究进展进行综述。     

经脑间质给药治疗帕金森病的研究新进展

帕金森病（PD）是一种常见的神经系统变性疾病,其致病因素除细胞功能紊乱及有毒物质作用外,细胞外微环境异常也逐渐受到关注,与此相关的前沿治疗方法主要包括对流增强给药和简单扩散给药,尤其后者的高效性及安全性已在多项研究中得到证实。现以脑间质治疗手段为基础,重点介绍国内学者研发的简单扩散给药在PD治疗领域的全新应用。     

Seeking progress in disease modification in Parkinson disease

ObjectiveDisease modification in Parkinson disease (PD) has remained an elusive goal, in spite of large investments over several decades. Following a large meeting of experts, this review article discusses the state of the science, possible reasons for past PD trials’ failures to demonstrate disease-modifying benefit, and potential solutions.MethodsThe National Institute of Neurological Disorders and Stroke (NINDS) convened a meeting including leaders in the field and representatives of key stakeholder groups to discuss drug therapy with the goal of disease modification in PD.ResultsImportant lessons can be learned from previous attempts, as well as from other fields. The selection process for therapeutic targets and agents differs among various organizations committed to therapeutic development. The areas identified as critical to target in future research include the development of relevant biomarkers, refinements of the targeted patient populations, considerations of novel trial designs, and improving collaborations between all stakeholders.ConclusionsWe identify potential barriers to progress in disease modification for Parkinson's and propose a set of research priorities that may improve the likelihood of success.     

Morphological alterations of the synapses in the locus coeruleus in Parkinson's disease

Parkinson's disease is the most common movement disorder in the broad spectrum of neurodegenerative diseases, associated frequently with gradual decline of the higher mental faculties. From the morphological point of view it is characterized by the degeneration of a substantial number of dopaminergic neurons of the substantia nigra and a considerable degeneration of neuronal networks in locus coeruleus, putamen, globus pallidus, thalamus and some areas of the cortex of the brain hemispheres. Filamentous inclusions, in the form of Lewy bodies and Lewy neuritis, composed mainly of alpha synuclein, been the hallmark of diffuse Lewy body dementia, have been described in the neurons of the substantia nigra in many cases of Parkinson's disease associated with dementia. In previous studies we have described the morphological alterations in the synapses in the caudate nucleus and the globus pallidus in cases of Parkinson's disease. In the present study we attempted to describe the morphological and morphometric alterations of the locus coeruleus in patients who suffered from Parkinson's disease with normal cognitive function and in patients who suffered from Parkinson's disease associated with dementia, comparing them with normal controls. The morphological alterations of the neurons, the dendrites, the retrograde axonic collaterals and the synapses were more impressive in cases of Parkinson's disease associated with dementia than in Parkinson's disease with normal cognitive function. The majority of the synapses demonstrated changes in size and shape of the pre- and postsynaptic components, polymorphism of the synaptic vesicles and marked morphological alterations of the mitochondria. The morphological alterations of the synapses in cases of Parkinson's disease associated with dementia, plead in favor of the importance of the neuronal circuits of locus coeruleus in cognitive functions.     

The role of the locus coeruleus in the development of Parkinson's disease

In Parkinson's disease, together with the classic loss of dopamine neurons of the substantia nigra pars compacta, neuropathological studies and biochemical findings documented the occurrence of a concomitant significant cell death in the locus coeruleus. This review analyzes the latest data obtained from experimental parkinsonism indicating that, the loss of norepinephrine in Parkinson's disease might worsen the dopamine nigrostriatal damage. Within this latter context, basic research provided a new provocative hypothesis on the significance of locus coeruleus in conditioning the natural history of Parkinson's disease. In particular, the loss of a trophic influence of these neurons might be crucial in increasing the sensitivity of nigrostriatal dopamine axons to various neurotoxic insults. In line with this, recently, it has been shown that locus coeruleus activity plays a pivotal role in the expression of various immediate early genes and in inducing the phosphorilation of cyclic adenosine monophosphate response element-binding proteins, suggesting a role of the nucleus in sustaining a protective effect.