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MRI evaluation of myelopathic pain after spinal cord injury or spinal cord tumor surgery 脊髓损伤或脊髓肿瘤手术后脊髓性疼痛的MRI评价
Pub Date : 2020-03-31 DOI: 10.11154/pain.35.34
Osahiko Tsuji, Kohei Matsubayashi, Yosuke Horiuchi, Yuji Komaki, J. Hata, Tsunehiko Konomi, K. Fujiyoshi, Shizuko Kosugi, M. Nakamura
Patients with spinal cord injury suffered from not only motor paralysis but also intolerable neuropathic pain. Regarding the mechanism, various theories such as functional changes in the brain, disorders within the spinal dorsal horn and/or spinothalamic tract have been proposed. However, the feasible animal models with solid reproducibility has been insufficiently verified. We have established the mice fMRI system, reported the results of mice–fMRI after L 5 nerve injury and resting state–fMRI imaging after thoracic cord transection injury in mice. Furthermore, in a clinical setting we evaluated the brain morphometry of the cases with spinal intra medullary tumor surgery by VBM, and found the gray matter volume of some brain regions was increased related with pain intensity. Besides fMRI and VBM analysis, we developed diffusion MRI techniques which could depict neuronal axons and myelination within the spinal cord (“diffusion tensor tractgraphy” and “myelin map”, respectively). In this review, I would like to outline our results of MRI analysis of neuropathic pain so far.
脊髓损伤患者不仅遭受运动麻痹,还遭受难以忍受的神经性疼痛。关于机制,已经提出了各种理论,如大脑的功能变化、脊髓背角和/或棘丘脑束内的疾病。然而,具有固体再现性的可行动物模型尚未得到充分验证。我们建立了小鼠功能磁共振成像系统,报道了小鼠L5神经损伤后的功能磁共振和小鼠胸脊髓横断损伤后的静息状态功能磁共振的成像结果。此外,在临床环境中,我们通过VBM评估了脊髓髓内肿瘤手术病例的大脑形态计量学,发现一些大脑区域的灰质体积随着疼痛强度的增加而增加。除了fMRI和VBM分析外,我们还开发了扩散MRI技术,可以描述脊髓内的神经元轴突和髓鞘形成(分别为“扩散张量束描记术”和“髓鞘图”)。在这篇综述中,我想概述我们迄今为止对神经性疼痛的MRI分析结果。
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引用次数: 0
The future of postsurgical pain management as envisaged from the perspective of preventing the development of chronic postsurgical pains 从预防慢性术后疼痛发展的角度展望术后疼痛管理的未来
Pub Date : 2020-03-31 DOI: 10.11154/pain.35.1
M. Iseki, K. Yamaguchi, A. Hara, Saeko Hamaoka, A. Kawai, Satoko Chiba
The importance of perioperative management has been emphasized in recent years so that patients who go through surgeries may return to their normal life as quickly as possible. In achieving this objective, pain management plays a key role in that alleviating pain in the earliest possible timing not only provides favorable effects both physically and psychologically but may also contribute toward preventing development of chronic postsurgical pains (CPSPs). While the actual risk of developing CPSP is comprised of a complex mixture of various factors before, during and after surgeries, 70 % of such pains are considered to be predictable based on clinical factors. In order to prevent the development of CPSP, then, finding high–risk patients from among those who are to go under surgeries and providing them with pre–surgery patient education as well as continuous postsurgical pain management and care by interdisciplinary teams should be helpful. The authors look forward to seeing more postsurgical pain management teams with anesthesiologists as their pivotal members to be formed in Japan.
围手术期管理的重要性近年来已被强调,以使患者通过手术可以尽快恢复正常生活。为了实现这一目标,疼痛管理在尽早减轻疼痛方面起着关键作用,不仅在生理和心理上都有良好的效果,而且可能有助于预防慢性术后疼痛(CPSPs)的发展。虽然发生CPSP的实际风险是由手术前、手术中和手术后各种因素的复杂混合组成的,但根据临床因素,70%的此类疼痛被认为是可预测的。因此,为了预防CPSP的发展,从手术患者中发现高危患者,并为他们提供术前患者教育以及跨学科团队持续的术后疼痛管理和护理应该是有帮助的。作者期待在日本建立更多以麻醉师为核心成员的术后疼痛管理团队。
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引用次数: 0
Seeking to realize tailor–made medicine for pain 寻求实现为疼痛量身定制的药物
Pub Date : 2020-03-31 DOI: 10.11154/pain.35.24
Yoshinori Takemura, M. Narita, N. Kuzumaki, M. Yamazaki
Although it is well known that pain varies from patient to patient, tailor–made medicine for patients in pain has not yet been realized. Anesthesiologists often encounter patients whose pain persists after surgery, even though could be managed before the operation. It can be difficult to alleviate such prolonged pain a generic. In the future, to respond to pain in individual patients, it will be necessary to analyze pain–related signals that reflect not only the findings captured in conventional images and examinations, but also the physiological state, genetic background, and the state of the disease in patients. We have been searching for pain–related signals through basic research. Our functional MRI studies showed that the pain pathway was activated if analgesics were not administered under general anesthesia during surgery. This induced epigenomic modification in the spinal cord and brain, which was speculated to lead to prolonged pain as well as secondary emotional and sleep disorders. We also found that cytokine storms caused by surgery were the source of prolonged pain. Furthermore, in microRNA (miRNA) studies, early peripheral neuropathy significantly increased the expression of several miRNAs caused by inflam matory cytokines in the dorsal root ganglia. This led to concomitant increases in the expression of inflammation–derived exosomal miRNAs in the blood. We believe these findings will provide new information for next–generation pain treatment. In the future, “stratify” pain patients, it will be necessary to collect informa tion from procedures such as liquid biopsies. Individual and common para meters can be created based on mathematical analysis, data compression, and clustering analysis. Based on this information, we will create highly limited and diverse animal models of by individually introducing pain parameter–induced genes, and study pathological analysis and treatment methods. If such translational pain research becomes possible, tailor–made medicine for pain will become closer to reality.
虽然疼痛因人而异是众所周知的,但为疼痛患者量身定制的药物尚未实现。麻醉师经常遇到手术后疼痛持续的病人,即使在手术前可以控制。一般来说,要缓解这种长期的疼痛是很困难的。在未来,为了对单个患者的疼痛做出反应,有必要分析疼痛相关信号,这些信号不仅反映了常规图像和检查中捕获的结果,还反映了患者的生理状态、遗传背景和疾病状态。我们一直在通过基础研究寻找与疼痛相关的信号。我们的功能性MRI研究表明,如果在手术中全身麻醉下不使用镇痛药,疼痛通路被激活。这引起了脊髓和大脑的表观基因组修饰,据推测,这导致了持续的疼痛以及继发性的情绪和睡眠障碍。我们还发现,手术引起的细胞因子风暴是长期疼痛的来源。此外,在microRNA (miRNA)研究中,早期周围神经病变显著增加了背根神经节中炎症细胞因子引起的几种miRNA的表达。这导致血液中炎症源性外泌体mirna的表达同时增加。我们相信这些发现将为下一代疼痛治疗提供新的信息。在未来,“分层”疼痛患者,将有必要从诸如液体活检等程序中收集信息。可以基于数学分析、数据压缩和聚类分析创建单独的和通用的参数。在此基础上,我们将通过单独引入疼痛参数诱导基因,建立高度有限和多样化的动物模型,并研究病理分析和治疗方法。如果这种转化性疼痛研究成为可能,那么针对疼痛的量身定制药物将更接近现实。
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引用次数: 0
Neuroimaging studies about the relationship between negative emotions and pain 关于消极情绪和疼痛关系的神经影像学研究
Pub Date : 2020-03-31 DOI: 10.11154/pain.35.17
A. Yoshino, Y. Okamoto, S. Yamawaki
Pain experience is strongly affected by emotions, and especially, negative emotions cause more painful perception. And as mechanisms of linking to chronic pain, negative emotions are also important factors. We have been gradually studying the association between negative emotions and painful perception, and we will review these relationship by using clinical symptoms and neuroimaging data. Our studies have been approved by the Hiroshima University ethics committee.
疼痛体验受情绪的强烈影响,尤其是负面情绪会引起更多的疼痛感知。作为与慢性疼痛相关的机制,负面情绪也是重要因素。我们一直在逐步研究负面情绪与疼痛感知之间的关系,我们将通过临床症状和神经影像学资料来回顾这些关系。我们的研究得到了广岛大学伦理委员会的批准。
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引用次数: 1
Brain activation in non–human primate pain model using functional MRI 非人类灵长类动物疼痛模型的脑激活功能磁共振成像
Pub Date : 2020-03-31 DOI: 10.11154/pain.35.45
Hiroki Ushirozako, G. Yoshida, T. Hasegawa, Yu Yamato, Takahiro Natsume, S. Ogawa, Y. Awaga, A. Hama, H. Takamatsu, Y. Matsuyama
Functional magnetic resonance imaging (fMRI) is expected as a biomarker of pain because it can objectively evaluate changes in cerebral blood flow associated with neuron activity against pain. We have developed pain models for cynomolgus macaques because it is more compatible with humans in regard to the structures and functions of brain regions which is suggested to be involved in pain in humans. Aside from humans, the cynomolgus macaques are the most widespread primate genus, ranging from Japan to North Africa. Since the macaques are the animal species closest to humans among those which can be used for invasive experiments, they are widely used to understand the mechanisms of the human brain. The purpose of this study is to elucidate pain–related brain activation regions in the macaque models using fMRI. Generally, pain testing in animal models has been based on avoidance behavior against pain stimuli. However, we identified pain– related brain activation regions using fMRI under propofol anesthesia as a more objective evaluation method. In the macaque model of chymopapain–induced discogenic low back pain, the activity of the insular cortex occurred in response to lumbar compression stimulation. In the macaque model of oxaliplatin–induced neuropathic cold hypersensitivity, activation of the insular cortex also occurred in response to cold stimuli. As a result of evaluating pregabalin, duloxetine and tramadol, only 者は増加の一途にあり,中でも腰痛に苦しむ患 者の数は非常に多く,さらに様々な原因によっ て生じるため,痛みによって賦活化される脳領 ing morphine, meloxicam and acetaminophen, only morphine showed behavioral effectiveness and suppressed activation of thalamus due to abdominal pain from endometriosis. It was suggested that the brain activation regions could change due to various conditions that can cause the pain, as the acute pain increased activation in the insula cortex and the chronic pain increased activation in the thalamus. This study demonstrated the usefulness of fMRI as a pain biomarker, and fMRI analysis using the macaques might provide an advantage for the translation of the findings to human patients. Therefore, these study will contribute to the development of new analgesics for each pain as well as to the progress in the areas of brain research.
功能性磁共振成像(fMRI)有望成为疼痛的生物标志物,因为它可以客观地评估与神经元对抗疼痛活动相关的脑血流量变化。我们开发了食蟹猕猴的疼痛模型,因为它在大脑区域的结构和功能方面与人类更兼容,而大脑区域被认为与人类的疼痛有关。除了人类,食蟹猴是分布最广的灵长类动物,从日本到北非都有。由于猕猴是可用于侵入性实验的动物中最接近人类的物种,因此它们被广泛用于了解人类大脑的机制。本研究的目的是使用功能磁共振成像来阐明猕猴模型中与疼痛相关的大脑激活区域。通常,动物模型中的疼痛测试是基于对疼痛刺激的回避行为。然而,我们在丙泊酚麻醉下使用fMRI作为一种更客观的评估方法,确定了疼痛相关的大脑激活区域。在木瓜蛋白酶诱导的椎间盘源性腰痛的猕猴模型中,岛叶皮层的活动是对腰部压迫刺激的反应。在奥沙利铂诱导的神经性冷超敏反应的猕猴模型中,岛叶皮层的激活也发生在对冷刺激的反应中。作为评估普瑞巴林、度洛西汀和曲马多的结果者は増加の一途にあり,中でも腰痛に苦しむ患 者の数は非常に多く,さらに様々な原因によっ て生じるため,痛みによって賦活化される脳領 与吗啡、美洛昔康和对乙酰氨基酚相比,只有吗啡表现出行为有效性,并抑制了子宫内膜异位症腹痛引起的丘脑激活。有人认为,大脑激活区域可能会因各种可能导致疼痛的条件而改变,因为急性疼痛增加了岛叶皮层的激活,慢性疼痛增加了丘脑的激活。这项研究证明了fMRI作为疼痛生物标志物的有用性,使用猕猴的fMRI分析可能为将研究结果转化为人类患者提供优势。因此,这些研究将有助于开发针对每种疼痛的新型止痛药,并有助于大脑研究领域的进展。
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引用次数: 0
Nerve growth factor (NGF) and its receptor TrkA —their relations with pain— 神经生长因子及其受体TrkA与疼痛的关系--
Pub Date : 2020-03-30 DOI: 10.11154/pain.37.7
K. Mizumura, Asako Kubo
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引用次数: 0
Changes of heat pain sensitivity during the menstrual cycle in Japanese young adults: a randomized trial 日本年轻人月经周期中热痛敏感性的变化:一项随机试验
Pub Date : 2019-12-20 DOI: 10.11154/pain.34.304
T. Kakeda, Kei Takani, Koichi Takaoka, Noriyoshi Tanaka, Y. Ogino
The aim of this study was to compare pain sensitivity between the follicular and luteal phases of the menstrual cycle in Japanese young adults. Fifteen females participat ed in this randomized control trial with crossover design. The pain threshold (defined as the temperature when the subject started to feel pain) was measured using a heat pain stimulator on the short flexor muscle of the thumb. For each subject, the stimulus was performed 10 times, alternating between the right and left hand. Pain reactivity was evaluated using a self–identified threshold of heat pain, salivary alpha amylase, emotional evaluation using a profile of mood states and visual analog scale scores. After comparative analysis, we found that pain threshold under the follicular phase was significantly increased compared to that under the luteal phase, indicating that the menstrual cycle would influence the severity of pain perception. Pain sensitivity under the luteal phase is more sensitive to nociceptive stimuli than those under the follicular phase. We therefore need to conduct pain management with paying heed to the menstrual cycle. Additionally, young women in reproductive–age should be more protective in pain management during the luteal phase of their menstrual cycle. This study was conducted during the follicular and luteal phases of the menstrual cycle. Heat pain stimuli were performed a total 10 times on the right and left hands, alternately. Moreover, subjects rested for 2 min between each heat pain stimulus to avoid any carryover effects and habituation to the heat pain stimulus. POMS: Profile of Mood States; VAS: Visual analogue scale; hand;
本研究的目的是比较日本年轻人月经周期卵泡期和黄体期的疼痛敏感性。本研究采用交叉设计,随机对照试验15例。疼痛阈值(定义为受试者开始感到疼痛时的温度)使用热痛刺激器在拇指短屈肌上测量。对每个受试者进行10次刺激,在右手和左手之间交替进行。疼痛反应性评估采用自我识别的热痛阈值,唾液α淀粉酶,情绪评估采用情绪状态和视觉模拟量表评分。经过对比分析,我们发现卵泡期的痛觉阈值较黄体期明显升高,说明月经周期会影响痛觉的严重程度。黄体期疼痛敏感性对伤害性刺激的敏感性高于卵泡期。因此,我们需要在进行疼痛管理时注意月经周期。此外,处于育龄期的年轻女性在经期黄体期的疼痛管理中应该更加保护自己。这项研究是在月经周期的卵泡期和黄体期进行的。热痛刺激右手和左手共10次,交替进行。此外,受试者在每次热痛刺激之间休息2分钟,以避免对热痛刺激的任何传导效应和习惯。心境状态谱;VAS:视觉模拟量表;手;
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引用次数: 0
Prevention of migraine during prodromal phase caused by weather changes 预防天气变化引起的前驱期偏头痛
Pub Date : 2019-12-20 DOI: 10.11154/pain.34.324
Kaku Taisyoku
Although migraine has been reported to have different inducing factors, changes in weather parameters such as atmospheric pressure, rain, humidity, temperature, wind, and lightning are well known important environmental factors. In recent years, reports of abnormal weather conditions such as heat waves in summer, heavy snow in winter, localized heavy rain, and abnormally light rain, as well as tropical cyclones are increasing. In today’s extreme weather conditions, the worsening, diver sification, and chronicity of migraine symptoms is concerning, and a higher level of treatment for migraine is required than ever before. Drug therapy is used as the principal treatment for migraine. If the acute treatment alone interferes with daily life, the principle is to combine daily preventive therapies to reduce the frequency, severity, and duration of the migraine attacks. However, there are several cases wherein migraine is poorly controlled only with their combination. Several patients with migraine experience prodromal symptoms, including stiff neck and shoulder as well as sensitivity to light and sound, before migraine attacks. In recent years, it has been reported that sensors for detecting atmospheric pressure exist in the vestibular part of the inner ear, and it has been shown that changes in atmospheric pressure may activate the vestibular nerve activity. We reported that difenidol, a vestibular nerve modulator, was administered to prevent or alleviate migraine attacks during the prodromal phase caused by change in weather. Prevention during the prodromal phase and prevention based on weather prediction are new treatment strategies for migraine. In today’s extreme weather conditions, 3 –P therapy that combines the three treatment strategies of prevention, prodrome, and prediction is useful.
尽管偏头痛有不同的诱发因素,但众所周知,大气压力、降雨、湿度、温度、风和闪电等天气参数的变化是重要的环境因素。近年来,有关夏季热浪、冬季大雪、局部大雨、异常小雨以及热带气旋等异常天气条件的报道越来越多。在今天的极端天气条件下,偏头痛症状的恶化、恶化和慢性化令人担忧,需要比以往任何时候都更高水平的偏头痛治疗。药物治疗被用作偏头痛的主要治疗方法。如果单独的急性治疗干扰了日常生活,原则是结合日常预防性治疗,以减少偏头痛发作的频率、严重程度和持续时间。然而,有几种情况下,偏头痛只有通过它们的组合才能得到很好的控制。一些偏头痛患者在偏头痛发作前会出现前驱症状,包括颈部和肩部僵硬以及对光和声音敏感。近年来,据报道,用于检测大气压力的传感器存在于内耳的前庭部分,并且已经表明,大气压力的变化可以激活前庭神经活动。我们报道了一种前庭神经调节剂地芬尼多尔,用于预防或缓解天气变化引起的前驱期偏头痛发作。前驱期预防和基于天气预测的预防是偏头痛的新治疗策略。在今天的极端天气条件下,结合预防、前驱症状和预测三种治疗策略的3-P治疗是有用的。
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引用次数: 0
Characteristics of chronic pain patients who complain weather–related pain and their exercise therapy 抱怨天气相关疼痛的慢性疼痛患者的特征及其运动治疗
Pub Date : 2019-12-20 DOI: 10.11154/pain.34.336
Hiroki Sakurai, Jun Sato, Shuichi Aono, Y. Arai, Shinsuke Inoue, Makoto Nishihara, N. Hatakeyama, Keiko Owari, H. Saisu, Izumi Makino, T. Ushida
Patients who complain of chronic pain have various symptoms and complicated pathologies, and there are often cases in which the symptoms worsen due to weather changes. However, few studies have examined the nature of pain affected by weather changes. In this time, we investigated the characteristics of patients with weather–related pain. As results, their pain intensity is moderate and they can maintain moderate daily activity. But in psychosocial factors, they have low self– efficacy and high catastrophic thinking. As treatment for chronic pain, exercise therapy managed by a therapist is highly recommended in non–drug therapy. Patients with weather–related pain often complain at head and neck shoulders. Evidences on the effects of exercise therapy for these body parts have also been reported. We hope that capturing the characteristics of patients with weather– related pain will lead to more appropriate treatments tailored to the pathological condition of the patients.
抱怨慢性疼痛的患者有各种各样的症状和复杂的病理,并且经常有由于天气变化而症状恶化的情况。然而,很少有研究调查受天气变化影响的疼痛的性质。在这段时间里,我们调查了天气相关疼痛患者的特征。因此,他们的疼痛强度适中,可以保持适度的日常活动。但在心理社会因素方面,他们的自我效能感较低,灾难性思维较高。作为慢性疼痛的治疗,在非药物治疗中,强烈建议由治疗师管理的运动疗法。天气相关疼痛的患者经常抱怨头部和颈部肩部疼痛。关于运动疗法对这些身体部位的影响的证据也有报道。我们希望,捕捉天气相关疼痛患者的特征将导致更适合患者病理状况的治疗。
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引用次数: 0
Mechanisms and treatment strategies of weather–related pain: In clinical settings 天气相关疼痛的机制和治疗策略:在临床设置
Pub Date : 2019-12-20 DOI: 10.11154/pain.34.316
H. Date, Akira Yamashiro, Hidekazu Watanabe
It is said that chronic pain turns worse when weather worsens than before. However, there are few articles showing weather and the relations of the pain. Our clinic is a medical institution of the pain clinic single department, and most of the patients having a medical examination are accompanied by chronic pain. In addition, we have the list Visual Analogue Scale (VAS) in all consultation patients foreign than 2013 at consultation. After checking association about the weather with VAS at consultation, in temperature, the humidity, the atmospheric pressure, it was thought that a change of the atmospheric pressure was related to the strength of the pain. By the disease distinction, we recognized meaningful correlation in herpes zoster referred pain, osteoarthritis of the knee, osteoarthritis of the hip in VAS at most atmospheric pressure drop quantity and consultation by the division at specific time.
据说,当天气比以前恶化时,慢性疼痛会变得更严重。然而,很少有文章显示天气和疼痛的关系。我诊所是疼痛门诊单科的医疗机构,就诊的患者大多伴有慢性疼痛。此外,我们有2013年以来所有会诊患者的视觉模拟量表(VAS)列表。在会诊时与VAS核对了天气、温度、湿度、气压的关联后,认为气压的变化与疼痛的强度有关。通过疾病的区分,我们发现带状疱疹牵涉性疼痛、膝关节骨关节炎、髋关节骨关节炎在VAS中最大大气压降量与特定时间分科会诊有显著相关性。
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引用次数: 0
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Pain Research
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