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Neurofeedback reveals mechanism of phantom limb pain to reduce pain 神经反馈揭示幻肢疼痛减轻疼痛的机制
Pub Date : 2021-04-30 DOI: 10.11154/pain.36.35
T. Yanagisawa
Phantom limb pain is an intractable pain for which no effective treatment has been establish ed. The pain has been attributed to abnormal plastic changes in the sensory motor cortex corresponding to the deafferented body part. Some feedback therapy such as mirror therapy have been applied to modify the abnormal cortical changes, although it is not been unveiled how to change the corresponding sensory motor cortex to reduce pain. We have applied neural decoding to magnetoencephalography (MEG) to extract motor information of the upper limb, and realized a Brain–Computer Interface (BCI) that allows patients to operate a prosthetic hand as if they were moving a phantom limb. In addition, we have demonstrated that neurofeedback (NF) training to control the BCI induced plastic changes in the patient’s sensorimotor cortex and changes in the pain. Actually, the training to attenuate the motor representation of the phantom limb reduced the pain. In addition, we evaluated the efficacy of the NF training by a blinded crossover trial of training with three consecutive days. Twelve patients were trained to control the phantom limb images, that were controlled through BCI. After three days NF trainings, the pain assessed with the Visual Analogue Scale (VAS) was significantly reduced for five days. Furthermore, the pain reduction was associated with the attenuation of the motor representation of phantom limb. These results suggest that the residual motor representations of phantom limb cause the phantom limb pain. We have demonstrated that the NF training elucidates the pathogenesis of chronic pain and develops a new treatment.
幻肢痛是一种顽固性疼痛,目前尚无有效的治疗方法。这种疼痛可归因于与失传入部位相对应的感觉运动皮层的异常可塑性变化。一些反馈疗法如镜像疗法已被应用于改变皮层的异常变化,但如何改变相应的感觉运动皮层以减轻疼痛尚不清楚。我们将神经解码技术应用于脑磁图(MEG),提取上肢的运动信息,并实现了脑机接口(BCI),使患者可以像移动幻肢一样操作假手。此外,我们已经证明,控制脑机接口的神经反馈(NF)训练会引起患者感觉运动皮层的可塑性变化和疼痛的变化。实际上,通过训练来减弱幻肢的运动表征减轻了疼痛。此外,我们通过连续三天的盲法交叉试验来评估NF训练的效果。12名患者接受训练,通过脑机接口控制幻肢图像。经过3天的NF训练后,视觉模拟评分(VAS)评估的疼痛明显减轻了5天。此外,疼痛减轻与幻肢运动表征的衰减有关。这些结果提示幻肢残余运动表征是引起幻肢疼痛的原因。我们已经证明,NF训练阐明了慢性疼痛的发病机制,并开发了一种新的治疗方法。
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引用次数: 0
Development of a Japanese version of the Pain Disability Index: translation and linguistic validation 日语版疼痛残疾指数的开发:翻译和语言验证
Pub Date : 2021-04-30 DOI: 10.11154/pain.36.1
Keiko Yamada, A. Mibu, Sonora Kogo, M. Iseki, Tomohiko Nishigami
The Pain Disability Index ( PDI ) is a self–reported outcome measure initially developed in English to assess disability caused by pain in seven dimensions of daily life activity, including family ⁄ home responsibilities, recreation, social activity, occupation, sexual behavior, self–care, and life–support activity. This study aimed to develop a linguistical ly valid Japanese version of the PDI ( PDI–J ) according to the guidelines for the translation and cultural adaptation of patient–reported outcome measures establish ed by the task force of the International Society for Pharmacoeconomics and Outcomes Research. A draft of the PDI–J was developed through a forward translation of the original PDI from English to Japanese, reconciliation of the translation, back– translation from Japanese to English, and harmonization. We subsequently conducted a cognitive debriefing in five patients using the PDI–J draft and reviewed it before finaliz ing a linguistically valid PDI–J. We also considered a five–item version of the PDI ( PDI–5–J ) , which excluded two items ( sexual behavior and life–support activity ) from the original version. This consideration was made for brevity and because sexual behavior is a considerably personal parameter that some patients may be reluctant to answer and life–support activity because it was considered ambiguous in Japanese. Therefore, we were able to develop a linguistically valid PDI–J and PDI–5–J through this process. Further study is warranted to confirm the psychometric validity and reliabili ty of the two indices
疼痛残疾指数(PDI)是一种自我报告的结果测量方法,最初是用英语开发的,用于评估日常生活活动中七个维度的疼痛引起的残疾,包括家庭责任、娱乐、社会活动、职业、性行为、自我照顾和生命支持活动。本研究旨在根据国际药物经济学和结果研究学会(International Society for Pharmacoeconomics and Outcomes Research)工作组制定的患者报告结果测量的翻译和文化适应指南,开发一种语言有效的日语版本PDI (PDI - j)。PDI - j的草案是通过原PDI从英语到日语的前译、翻译的协调、从日语到英语的后译和协调而发展起来的。随后,我们使用PDI-J草案对5名患者进行了认知情况汇报,并在最终确定语言有效的PDI-J之前对其进行了审查。我们还考虑了PDI的五项版本(PDI - 5 - j),它从原始版本中排除了两个项目(性行为和生命支持活动)。这样做是为了简洁,因为性行为是一个相当个人化的参数,一些患者可能不愿意回答,而生命维持活动在日语中被认为是模糊的。因此,通过这个过程,我们能够开发出语言上有效的PDI-J和PDI-5-J。这两个指标的心理测量效度和信度有待进一步研究
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引用次数: 1
Association between cluster analysis for multiple measures and International Classification of Diseases 11th revision as classification of chronic pain patients 多指标聚类分析与《国际疾病分类》第11版作为慢性疼痛患者分类的关系
Pub Date : 2020-09-30 DOI: 10.11154/PAIN.35.141
A. Kawai, Keiko Yamada, Saeko Hamaoka, Satoko Chiba, K. Wakaizumi, K. Yamaguchi, M. Iseki
Cluster analysis can classify patients with chronic pain using multiple scales, and classification of chronic pain will be adopted in the International Classification of Diseases 11 th revision (ICD– 11 ) in 2022 . In the present study, we aimed to investi-gate whether cluster analysis was practical for classifying chronic pain and to determine the association between these two classifications for chronic pain. This study included 229 patients with chronic pain who completed a self–reported questionnaire at the first visit to a pain clinic in a university hospital. Patients were clustered using a two–step cluster analysis (TSCA), a machine learning method, for the scores of nine questionnaires. Thereafter, the proportions of clusters among major and several minor classifications were tested using the analysis of covariance adjusted for age and doctor. The following three clusters were calculated using TSCA: mild, moderate, and severe symptoms. Among the major classifications of chronic pain in ICD– 11 , the distribution of clusters significantly differed, but the proportions of these three clusters in each chronic pain classification did not differ. Our findings suggested that TSCA for multiple measures may be a better approach for the classification of chronic pain, but its classification is not associated with the classification of chronic pain in ICD– 11 . The P–values of chronic widespread primary pain and others were calculated for comparison with chronic localized primary pain by the analysis of covariance using Dunnett’s test. The P–values of chronic centralized and other neuropathic pain were calculated for comparison with chronic peripheral neuropathic pain by the analysis of covariance using Dunnett’s test. The P–values of chronic non–specific and other pain were calculat ed for comparison with chronic structurally changed musculoskeletal pain by the analysis of covariance using Dunnett’s test. The analysis of covariance was adjusted for age and doctor.
聚类分析可以使用多个尺度对慢性疼痛患者进行分类,慢性疼痛的分类将在2022年国际疾病分类第11次修订(ICD - 11)中采用。在本研究中,我们旨在探讨聚类分析是否适用于慢性疼痛分类,并确定这两种分类之间的关系。这项研究包括229名慢性疼痛患者,他们在第一次去大学医院的疼痛诊所时完成了一份自我报告问卷。患者使用两步聚类分析(TSCA),一种机器学习方法,对九份问卷的分数进行聚类。然后,使用协方差分析对年龄和医生进行调整,检验主要和几个次要分类之间的聚类比例。使用TSCA计算以下三个聚类:轻度、中度和重度症状。在ICD - 11的主要慢性疼痛分类中,聚类分布有显著差异,但这三种聚类在各慢性疼痛分类中的占比无显著差异。我们的研究结果表明,多种测量方法的TSCA可能是一种更好的慢性疼痛分类方法,但其分类与ICD - 11中的慢性疼痛分类无关。采用Dunnett检验进行协方差分析,计算慢性广漫性原发性疼痛和其他慢性局限性原发性疼痛的p值,并与慢性局限性原发性疼痛进行比较。采用Dunnett检验进行协方差分析,计算慢性集中性和其他神经性疼痛的p值,与慢性周围神经性疼痛进行比较。采用Dunnett检验进行协方差分析,计算慢性非特异性疼痛和其他疼痛的p值,并与慢性结构改变的肌肉骨骼疼痛进行比较。协方差分析对年龄和医生进行了调整。
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引用次数: 0
Characteristics of pain–related factors in subgroups based on central sensitivity syndromes and pain in musculoskeletal pain patients: a cluster analysis 基于中枢敏感综合征和肌肉骨骼疼痛患者疼痛亚组的疼痛相关因素特征:聚类分析
Pub Date : 2020-09-30 DOI: 10.11154/PAIN.35.133
H. Shigetoh, Yoichi Tanaka, Masayuki Koga, M. Osumi, S. Morioka
Central sensitization (CS) and psychological factors are associated with pain intensity. However, it has remained unclear whether the effects of central sensitivity syndromes and cognitive ⁄ emotional factors differ depending on the severity of pain and the pain quality. Our purposes were to perform subgrouping based on central sensitivity syndromes and pain intensity, and to clarify the difference in central sensitization syndrome and pain intensity between subgroups. Fifty–nine patients with musculoskeletal pain were included in this cross– sectional study. Pain intensity and psychological problems were assessed with Central sensitization inventory (CSI–9), Short–Form McGill Pain Questionnaire 2 (SFMPQ2), Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS–4). The cluster analysis with a ward method was used to divide patients into subgroups based on central sensitization syndrome and pain intensity. In addition, Kruskal–Wallis test, multiple comparison (Bonferroni method), and Fisher’s exact test were performed to compare clinical outcomes between subgroups. The level of significance was set at 5%. The cluster analysis classified into three subgroups. One subgroup of patients (n=11) was characterized by high level of central sensitivity syndromes, pain intensity and psychological problems. A second subgroup (n=19) was characterized by low level of central sensitivity syndromes, moderate level of pain intensity, high level of psychological problems. The third subgroup (n=29) was characterized by low level of central sensitivity syndromes, pain intensity and psychological problems. That is, one subgroup was mainly affected with central sensitivity syndromes, and another subgroup was affected psychological factors. These results indicated the differences in pain mechanism among subgroups.
中枢致敏(CS)和心理因素与疼痛强度有关。然而,目前尚不清楚中枢敏感综合征和认知/情绪因素的影响是否因疼痛的严重程度和疼痛质量而异。我们的目的是根据中枢敏感综合征和疼痛强度进行亚组,并澄清亚组之间中枢敏感综合症和疼痛强度的差异。59名肌肉骨骼疼痛患者被纳入这项横断面研究。使用中心致敏量表(CSI-9)、简式麦吉尔疼痛问卷2(SFMPQ2)、医院焦虑和抑郁量表(HADS)、疼痛灾难量表(PCS-4)评估疼痛强度和心理问题。采用病房法进行聚类分析,根据中枢致敏综合征和疼痛强度将患者分为亚组。此外,还进行了Kruskal–Wallis检验、多重比较(Bonferroni法)和Fisher精确检验,以比较亚组之间的临床结果。显著性水平设定为5%。聚类分析分为三个亚组。一个亚组患者(n=11)的特点是中枢敏感综合征、疼痛强度和心理问题高。第二个亚组(n=19)的特征是中枢敏感性综合征水平低,疼痛强度中等,心理问题水平高。第三亚组(n=29)的特点是中枢敏感性综合征、疼痛强度和心理问题水平低。也就是说,一个亚组主要受中枢敏感性综合征的影响,另一个亚群受心理因素的影响。这些结果表明了亚组之间疼痛机制的差异。
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引用次数: 0
Investigation of influence factors on chronic pain in each generation 各代慢性疼痛影响因素的调查
Pub Date : 2020-06-30 DOI: 10.11154/pain.35.107
Y. Terajima, Yukiko Shiro, Shuichi Aono, Keiko Owari, Kenichi Arai, Shinsuke Inoue, T. Matsubara, Makoto Nishihara, T. Ushida
Purpose: The aim of this study is to clarify the difference in influencing factors for chronic pain in each generation. Method: There were 2 , 298 patients who visited Aichi Medical University Pain Center. The patient pedestrian score measured using iPad at the first visit was analyzed. Measurement items are Numerous Rating Scale (NRS), Pain Disability Assessment Scale (PDAS), Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), Pain Self–Efficacy Questionnaire (PSEQ), and Athens Insomnia Scale (AIS). For these items, average values were calculated for each age group of 10 years. Furthermore, linear regression was performed using NRS and PDAS as objective variables and other items as explanatory variables. A p value < 0 . 05 was considered significant. Result: NRS, PDAS and PCS were high after the 30 s, HADS and AIS were high in the working generation, and PSEQ was low in the working generation. The number of patients is the lowest in teens and increased in the 40 s, and there were many patients in the subsequent generations, with the largest number of men and women in their 60 s. In the multiple regression analysis with NRS as the objective variable, AIS was selected with a significant difference in the generations excluding the 80 s. In the 20 s and 70 s, PCS was selected. In the multiple regression analysis with PDAS as the objective variable, AIS was selected in the teens to 60 s, PSEQ was selected in the 30 s and over, and HADS depression was selected in the 40 s and over. Conclusion: We analyzed pain–related factors for each generation and found dif-ferences between generations. The working generation was worse in psychology and sleep than the other generations, and these affected pain symptoms.
目的:本研究的目的是阐明每代人慢性疼痛的影响因素的差异。方法:对前来爱知医科大学疼痛中心就诊的2298例患者进行分析。分析首次就诊时使用iPad测量的患者步行评分。测量项目有:众多评定量表(NRS)、疼痛残疾评定量表(PDAS)、医院焦虑抑郁量表(HADS)、疼痛灾难化量表(PCS)、疼痛自我效能问卷(PSEQ)和雅典失眠量表(AIS)。对于这些项目,计算了每个10岁年龄组的平均值。此外,以NRS和PDAS为客观变量,其他项目为解释变量进行线性回归。p值< 0。05被认为是显著的。结果:30年代后NRS、PDAS、PCS较高,工作代HADS、AIS较高,工作代PSEQ较低。患者在十几岁时最少,40多岁时增加,以后几代患者较多,60多岁的男女患者最多。在以NRS为目标变量的多元回归分析中,选择AIS,除80年代外,各代间差异显著。在20年代和70年代,PCS被选中。在以PDAS为客观变量的多元回归分析中,青少年至60多岁选择AIS, 30多岁及以上选择PSEQ, 40多岁及以上选择HADS抑郁。结论:我们分析了每代人的疼痛相关因素,发现了各代人之间的差异。工作一代在心理和睡眠方面比其他几代人差,这些都影响了疼痛症状。
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引用次数: 0
Central sensitization and chronic pain: study for migraine 中枢致敏与慢性疼痛:偏头痛的研究
Pub Date : 2020-06-30 DOI: 10.11154/pain.35.73
K. Hirata, D. Danno, S. Kikui, Keisuke Suzuki, T. Takeshima
Refractory chronic headaches greatly impair the quality of life of migraine patients and also reduce social productivity. To elucidate the pathophysiology of the supersensitive brain state of refractory migraine attacks, and to discover the treatment and prophylaxis for the refractory chronic migraine, we analyzed a brain electric field under the light stimulation–induced brain supersensitivity. As a result, we found suppression of the cortical hyperexcitation only in patients with migraine without aura. This result suggested that the suppression of the cortical hyperexcitation by cortical spreading depression may have a role for inhibition of excitation in limbic system, vestibular system and the vomiting center. Next, cranial autonomic symptoms in patients with migraine have recently received attention. We showed that central sensitization, assessed by central sensitization inventory questionnaire, was more prevalent in migraine patients with cranial autonomic symptoms compared with those without cranial autonomic symptoms, suggesting a possible role of central sensitization in comorbid autonomic symptoms in migraine. Central sensitization is postulated to participate in not only severe pain but also in various symptoms such as fatigue, sleep disturbances, anxiety and depres sion in chronic pain syndrome. We believe our study results from migraine patients shed some light on the role of central sensitization in pathophysiology of chronic pain syndrome, but the elucidation of these relationships require further studies.
难治性慢性头痛严重影响偏头痛患者的生活质量,降低社会生产力。为阐明难治性偏头痛发作时脑超敏状态的病理生理,探索难治性慢性偏头痛的治疗和预防方法,我们分析了光刺激下脑超敏状态下的脑电场。结果,我们发现只有在没有先兆的偏头痛患者中才有皮质亢进的抑制。提示皮质扩张性抑制对皮质过度兴奋的抑制可能对边缘系统、前庭系统和呕吐中枢的兴奋有抑制作用。其次,偏头痛患者的颅自主神经症状最近受到关注。我们发现,通过中枢致敏问卷评估,中枢致敏在有颅自主神经症状的偏头痛患者中比没有颅自主神经症状的患者更普遍,这表明中枢致敏可能在偏头痛共病的自主神经症状中起作用。据推测,中枢致敏不仅参与剧烈疼痛,还参与慢性疼痛综合征中的疲劳、睡眠障碍、焦虑和抑郁等各种症状。我们相信偏头痛患者的研究结果揭示了中枢致敏在慢性疼痛综合征病理生理学中的作用,但这些关系的阐明需要进一步的研究。
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引用次数: 0
Shuttle maze test: A novel operant method to repeatedly assess presumed nociception in freely behaving rats after nerve injury 穿梭迷宫试验:一种可重复评估自由行为大鼠神经损伤后推定伤害感受的新方法
Pub Date : 2020-06-30 DOI: 10.11154/pain.35.92
Ken-ichiro Hayashida
Operant methods that allow animals to avoid painful stimuli are interpreted to assess the aversive quality of pain, however, such measurements involve stimulation delivery by the experimenter and can induce fear, anxiety, or stress in animals, all of which can affect nociceptive threshold or mask pain behaviors. Here we developed a new operant method, the shuttle maze test, to assess the aversive quality of mecha nical stimuli in rats after L5–L6 spinal nerve ligation (SNL) without externally applied stimuli by the experimenter. The shuttle maze test is based on the motivation for chocolate flavor cereal as a treat, and animals ambulates back and forth between two treat feeders by taking either a short route with a prickly–surfaced arch or a longer route with a smooth floor. The preference for taking the short route is a primary outcome measure of the test. Importantly, the animals do not have any painful consequences of not performing the task in the shuttle maze. SNL reduced the preference for the short route with the arch, correlated with hypers ensitivity in the hindpaw. Oral gabapentin (30 and 100 mg/kg), pregabalin (100 mg/kg), and duloxetine (50 mg/kg) restored the short route preference and reduced hypersensitivity in SNL rats. These results suggest that SNL injury alters behavior in the shuttle maze test and that shuttle maze test shows comparable results to reflexive hypersensitivity after SNL in response to analgesics.
允许动物避免疼痛刺激的操作方法被解释为评估疼痛的厌恶质量,然而,这种测量涉及实验者的刺激传递,并可能在动物中引发恐惧、焦虑或压力,所有这些都会影响伤害阈值或掩盖疼痛行为。在这里,我们开发了一种新的操作方法,穿梭迷宫测试,以评估L5–L6脊神经结扎(SNL)后大鼠在没有实验者外部施加刺激的情况下机械刺激的厌恶质量。穿梭迷宫测试是基于巧克力口味谷物作为食物的动机,动物在两个食物喂食器之间来回走动,要么走一条有刺的拱形短路线,要么走地板光滑的长路线。选择短路线是测试的主要结果衡量标准。重要的是,这些动物不会因为没有在穿梭迷宫中执行任务而产生任何痛苦的后果。SNL降低了对有足弓的短路线的偏好,这与后爪的超敏反应有关。口服加巴喷丁(30和100 mg/kg)、普瑞巴林(100 mg/kg)和度洛西汀(50 mg/kg)恢复了SNL大鼠的短程偏好并降低了超敏反应。这些结果表明,SNL损伤改变了穿梭迷宫试验中的行为,穿梭迷宫试验显示出与SNL后对镇痛药的反射性超敏反应相当的结果。
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引用次数: 0
Roles of mesocortico–limbic system in exercise–induced hypoalgesia 中皮质-边缘系统在运动性痛觉减退中的作用
Pub Date : 2020-06-30 DOI: 10.11154/pain.35.80
K. Kami, F. Tajima, E. Senba
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引用次数: 0
Multifaceted evaluation of central post–stroke pain 中枢性脑卒中后疼痛的多方面评估
Pub Date : 2020-06-30 DOI: 10.11154/pain.35.99
N. Mori, K. Hosomi, M. Shibata, H. Kishima, Y. Saitoh
Objective: The goal of treating chronic pain is becoming more focused on improving ADL and QOL than on pain itself. In this study, we evaluated patients with central post–stroke pain (CPSP) by a multifaceted evaluation and examined factors related to ADL and QOL. Methods: Patient background, stroke information, motor and sensory disturbance, pain site and duration, pain scales (VAS and Short–form McGill Pain Questionnaire 2 ; SF–MPQ 2 ), Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale (HADS), Pain Disability Assessment Scale (PDAS), EQ– 5 D– 5 L were obtained from 41 patients with CPSP. The factors related to PDAS and EQ– 5 D– 5 L were investigated by univariate and multivariate analyses. Results: The univariate analysis showed that the PDAS was associated with motor disturbance scale (SIAS–motor: r=− 0 . 67 , p< 0 . 01 ) and pain scales (VAS: r= 0 . 32 , p= 0 . 04 ; SF–MPQ 2 : r= 0 . 31 ; p= 0 . 04 ), while the QOL value (EQ– 5 D– 5 L) was associated with motor disturbance scale (SIAS–motor: r= 0 . 55 , p< 0 . 01 ), pain scales (SF–MPQ 2 : r=− 0 . 54 , p< 0 . 01 ; VAS: r=− 0 . 48 , p< 0 . 01 ), degree of sensory disturbance (p< 0 . 01 ), and mood status (HADS depression item: r=− 0 . 56 , p< 0 . 01 ; HADS anxiety item: r=− 0 . 37 , p< 0 . 01 ). In multivariate analysis, the PDAS was largely affected by SIAS–motor and SF–MPQ 2 , and the QOL value was affected by multiple factors such as the SIAS–motor, SF–MPQ 2 , degree of sensory disturbance and HADS depression item. Conclusions: The ADL and QOL in patients with CPSP reflect not only pain, but also motor and sensory impairments, and mood status, which should be noted when assessing.
目的:治疗慢性疼痛的目标越来越侧重于改善日常生活能力和生活质量,而不是疼痛本身。在这项研究中,我们通过多方面评估来评估中心性卒中后疼痛(CPSP)患者,并检查与ADL和生活质量相关的因素。方法:从41例CPSP患者中获得患者背景、中风信息、运动和感觉障碍、疼痛部位和持续时间、疼痛量表(VAS和简式麦吉尔疼痛问卷2;SF–MPQ 2)、疼痛灾难量表、医院焦虑和抑郁量表(HADS)、疼痛残疾评估量表(PDAS)、EQ–5 D–5L。通过单变量和多变量分析研究了与PDAS和EQ–5 D–5 L相关的因素。结果:单因素分析显示,PDAS与运动障碍量表(SIAS–运动:r=-0.67,p<0.01)和疼痛量表(VAS:r=0.32,p=0.04;SF–MPQ 2:r=0.31;p=0.04)相关,而QOL值(EQ–5D–5L)与运动障碍度表相关(SIAS-运动:r=0.55,p<0.01),疼痛量表(SF–MPQ 2:r=−0.54,p<0.01;VAS:r=−0.48,p<01)、感觉障碍程度(p<0.01)和情绪状态(HADS抑郁项目:r=–0.56,p<0.001;HADS焦虑项目:r=−0.37,p<0.1)。在多变量分析中,PDAS在很大程度上受SIAS–运动和SF–MPQ 2的影响,QOL值受SIAS-运动、SF–MPQ2、感觉障碍程度和HADS抑郁项目等多个因素的影响。结论:CPSP患者的ADL和QOL不仅反映疼痛,还反映运动和感觉障碍以及情绪状态,在评估时应注意这一点。
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引用次数: 0
Right–side predominance of the central amygdala activation in trigeminal inflammatory pain model 三叉神经炎性疼痛模型中中央杏仁核激活的右侧优势
Pub Date : 2020-03-31 DOI: 10.11154/pain.35.10
Yukari Takahashi, Yuta Miyazawa, Daigo Arimura, Y. Sugimura, F. Kato
The central amygdala (CeA), especially the capsular part (CeC), receives nociceptive information from the superficial layer of the spinal dorsal horn and the caudal subnucleus of the trigeminal nucleus via the lateral parabrachial nucleus (LPB). The synapse between LPB and CeC neurons, forming the final stage of this spino–(trigemino–)parabrachio–amygdaloid pathway, undergoes robust synaptic potentiation in various types of rodent pain models, thus contributing to the enhanced nociception–emotion link in persistent pain. A remarkable feature of the CeA activation in animals with inflammatory pain is the right–side predominance. Using a trigeminal pain model by injecting formalin to the upper lip unilaterally, we analyzed the right–left differences in LPB–CeC synaptic potentiation and c–Fos expression in the LPB and the amygdala to reveal what determines the right– predomi nance in CeA activation. Unilateral trigeminal inflammation induced 1 ) a significant bilateral increase in c–Fos–expression in the LPB, 2 ) a right–predominant LPB–CeC synaptic potentiation and 3 ) a right–predominant increase in c– Fos–expression in the CeA, regardless of the side of the inflammation. Though c– Fos expression in the basolateral amygdala (BLA) was not significantly increased in this model, the number of c–Fos positive cells between the BLA and CeA was cor-related compared to that between the LPB and CeA. Therefore, the right–side predominance of the CeA activation in the inflammatory pain models would not be a simple consequence of lateralized LPB activation but rather involves non–Hebbian plasticity inherent to the CeA neurons and inputs they receive.
中央杏仁核(CeA),尤其是包膜部分(CeC),通过臂旁外侧核(LPB)接收来自脊髓背角浅层和三叉神经核尾侧亚核的伤害性信息。LPB和CeC神经元之间的突触形成了这种棘-(三叉神经-)臂旁-杏仁核通路的最后阶段,在各种类型的啮齿动物疼痛模型中经历了强大的突触增强,从而有助于增强持续疼痛中的伤害感受-情绪联系。炎症性疼痛动物的CeA激活的一个显著特征是右侧优势。使用单侧上唇注射福尔马林的三叉神经疼痛模型,我们分析了LPB和杏仁核中LPB–CeC突触增强和c–Fos表达的左右差异,以揭示是什么决定了CeA激活的右前效应。单侧三叉神经炎症诱导1)LPB中c–Fos–表达的双侧显著增加,2)右侧为主的LPB–CeC突触增强,3)无论炎症的哪一侧,CeA中c–Fos–表达都以右侧为主。尽管在该模型中,基底外侧杏仁核(BLA)中的c–Fos表达没有显著增加,但与LPB和CeA相比,BLA和CeA之间的c–Fos阳性细胞数量是相关的。因此,在炎性疼痛模型中,CeA激活的右侧优势不是LPB侧化激活的简单结果,而是涉及CeA神经元固有的非Hebbian可塑性及其接受的输入。
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Pain Research
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