• 【在逆行标记的突触后背柱神经元中没有FOS标记的情况下,存在神经损伤引起的触觉异常性疼痛。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2007-05-01
    来源期刊:Pain
    DOI:10.1016/j.pain.2006.10.009 复制DOI
    作者列表:Zhang ET,Ossipov MH,Zhang DQ,Lai J,Porreca F
    BACKGROUND & AIMS: :The dorsal column pathway consists of direct projections from primary afferents and of ascending fibers of the post-synaptic dorsal column (PSDC) cells. This pathway mediates touch but may also mediate allodynia after nerve injury. The role of PSDC neurons in nerve injury-induced mechanical allodynia is unknown. Repetitive gentle, tactile stimulus or noxious pinch was applied to the ipsilateral hindpaw of rats with spinal nerve ligation (SNL) or sham surgery that had previously received tetramethylrhodamine dextran in the ipsilateral n. gracilis. Both touch and noxious stimuli produced marked increases in FOS expression in other cells throughout all laminae of the ipsilateral dorsal horn after nerve injury. However, virtually none of the identified PSDC cells expressed FOS immunofluorescence in response to repetitive touch or pinch in either the nerve-injured or sham groups. In contrast, labeled PSDC cells expressed FOS in response to ureter ligation and labeled spinothalamic tract (STT) cells expressed FOS in response to noxious pinch. Identified PSDC neurons from either sham-operated or SNL rats did not express immunoreactivity to substance P, CGRP, NPY, PKCY, MOR, the NK1 and the NPY-Y1 receptor. Retrogradely labeled DRG cells of nerve injured rats were large diameter neurons, which expressed NPY, but no detectable CGRP or substance P. Spinal nerve injury sensitizes neurons in the spinal dorsal horn to repetitive light touch but PSDC neurons apparently do not participate in touch-evoked allodynia. Sensitization of these non-PSDC neurons may result in activation of projections integral to the spinal/supraspinal processing of enhanced pain states and of descending facilitation, thus priming the central nervous system to interpret tactile stimuli as being aversive.
    背景与目标: : 背柱途径由初级传入的直接投射和突触后背柱 (PSDC) 细胞的上升纤维组成。该途径介导触摸,但也可能介导神经损伤后的异常性疼痛。PSDC神经元在神经损伤引起的机械性异常性疼痛中的作用尚不清楚。重复的轻柔,触觉刺激或有害的捏合作用被应用于患有脊神经结扎 (SNL) 或假手术的大鼠的同侧后爪,这些大鼠先前在同侧gracilis中接受了四甲基罗丹明葡聚糖。神经损伤后,在同侧背角的所有层中,触摸和有害刺激均使其他细胞中的FOS表达显着增加。然而,在神经损伤或假手术组中,几乎没有鉴定出的PSDC细胞响应于重复触摸或捏合而表达FOS免疫荧光。相反,标记的PSDC细胞响应输尿管结扎表达FOS,而标记的脊髓丘脑束 (STT) 细胞响应有害的挤压表达FOS。鉴定出的来自假手术或SNL大鼠的PSDC神经元对p物质,CGRP,NPY,PKCY,MOR,NK1和NPY-Y1受体不表达免疫反应性。神经损伤大鼠逆行标记的DRG细胞为大直径神经元,表达NPY,但未检测到CGRP或p物质。脊神经损伤使脊髓背角的神经元对重复的轻触敏感,但PSDC神经元显然不参与触摸诱发的异常性疼痛。这些非PSDC神经元的敏化可能导致增强的疼痛状态和下降的促进作用的脊髓/脊髓上处理的投影的激活,从而引发中枢神经系统将触觉刺激解释为令人厌恶的。
  • 【带状疱疹后神经痛中疼痛,异常性疼痛和热感觉的关系。】 复制标题 收藏 收藏
    DOI:10.1093/brain/119.2.347 复制DOI
    作者列表:Rowbotham MC,Fields HL
    BACKGROUND & AIMS: In the syndrome of post-herpetic neuralgia (PHN), the nature of the sensory disturbance and its relationship both to the severity and cause of the pain is controversial. To address these issues, sensory mapping and quantitative thermal sensory testing was carried out four times in separate sessions on 35 subjects with established PHN. All subjects had pain affecting the torso or extremities and brush-evoked allodynia. Each session included rating of ongoing pain, mapping of the area of any sensory disturbance and the area of greatest pain, grading of allodynia severity within the area of greatest ongoing pain, and quantitative testing of thermal sensation in both the painful and the contralateral unaffected mirror-image skin. The severity of allodynia was positively correlated with reported ongoing pain severity. As a group, subjects had a sensory deficit to thermal stimuli in PHN skin compared with unaffected mirror-image skin. However, the magnitude of the heat pain sensory deficit was inversely correlated with both pain intensity and severity of allodynia. In fact, 12 subjects had heat hyperalgesia in their region of maximum pain. Compared with the 23 subjects with heat hypoalgesia, the group of 12 heat hyperalgesic subjects had significantly higher pain ratings and allodynia severity. Sensory loss was less strongly, but still inversely related to pain severity for the thermal modalities of innocuous warming, cooling and cold pain. This implies that there is no simple relationship between loss of peripheral nerve function and spontaneous or evoked pain. Rather, the preservation of several sensory modalities in their area of maximal pain suggests that in some PHN patients, activity in primary afferent nociceptors that remain connected to both their peripheral and central targets contributes significantly to ongoing pain. Although other mechanisms are likely to contribute to the pain, the demonstrated responsivity of PHN to topical agents including local anaesthetics, capsaicin, and non-steroidal anti-inflammatory drugs, supports this proposed mechanism of pain generation.

    背景与目标: 在带状疱疹后神经痛 (PHN) 综合征中,感觉障碍的性质及其与疼痛的严重程度和原因的关系是有争议的。为了解决这些问题,在35个已建立PHN的受试者中,分别进行了四次感官映射和定量热感官测试。所有受试者都有影响躯干或四肢的疼痛和刷子诱发的异常性疼痛。每个疗程包括持续疼痛的评分,任何感觉障碍区域和最大疼痛区域的映射,最大持续疼痛区域内的异常性疼痛严重程度的分级,以及对疼痛和对侧未受影响的镜像皮肤的热感觉的定量测试。异常性疼痛的严重程度与报告的持续疼痛严重程度呈正相关。作为一组,与未受影响的镜像皮肤相比,受试者对PHN皮肤的热刺激感觉不足。然而,热痛感觉缺陷的程度与疼痛强度和异常性疼痛的严重程度呈负相关。实际上,有12名受试者在其最大疼痛区域存在热痛觉过敏。与23例热痛觉低下的受试者相比,12例热痛觉过敏受试者的疼痛等级和异常性疼痛严重程度明显更高。感觉损失不那么强烈,但对于无害的变暖,降温和冷痛的热方式,其疼痛程度仍与疼痛严重程度成反比。这意味着周围神经功能丧失与自发性或诱发性疼痛之间没有简单的关系。相反,在其最大疼痛区域保留几种感觉方式表明,在某些PHN患者中,与周围和中心目标保持联系的主要传入伤害感受器的活动显着导致持续的疼痛。尽管其他机制可能会导致疼痛,但已证明PHN对局部药物 (包括局部麻醉剂,辣椒素和非甾体抗炎药) 的反应性支持了这种提出的疼痛产生机制。
  • 【痛苦的幻觉: 预先存在的知识决定了大脑对 “想象的异性障碍” 的激活。】 复制标题 收藏 收藏
    DOI:10.1016/j.jpain.2008.01.340 复制DOI
    作者列表:Krämer HH,Stenner C,Seddigh S,Bauermann T,Birklein F,Maihöfner C
    BACKGROUND & AIMS: UNLABELLED:Allodynia means that innocuous tactile stimulation is felt as pain. Accordingly, cerebral activations during allodynia or touch should markedly differ. The aim of this study was to investigate whether the imagination of allodynia affects brain processing of touch in healthy subjects. Seventeen healthy subjects divided into 2 subgroups were investigated: The first group (n = 7) was familiar with allodynia, based on previous pain studies, whereas the second group (n = 10) had never knowingly experienced allodynia. Using functional magnetic resonance imaging, 2 experimental conditions were investigated. In one condition the subjects were simply touched at their left hand, whereas during the other condition they were asked to imagine pain (allodynia) during tactile stimulation of the right hand and to estimate the imagined pain on a numeric rating scale. Data processing and analysis were performed with the use of SPM5. The group analysis of all subjects revealed that tactile stimulation activated contralateral somatosensory cortices (S1 [primary] and S2 [secondary]), but the imagination of allodynia led to an additional activation of anterior cingulate cortex and bilateral activation of S2, insular cortex, and prefrontal cortices. Subgroup analysis using rating-weighted predictors revealed activation of the contralateral thalamus, anterior cingulate cortex, and amygdala and a bilateral activation of S1, S2, and insular cortex and prefrontal cortices in allodynia-experienced subjects. In contrast, allodynia-inexperienced subjects only activated contralateral S1 and bilateral S2. Just the imagination that touch is painful is able to partly activate the central pain system, but only when the subject has previous experience of this. According to our results, the medial pain system is involved in the encoding of imagined allodynia. PERSPECTIVE:This article reports that pain experience is able to alter central processing of sensory stimuli. Pain knowledge appears to be able to shift "normal" tactile processing to a different quality, resulting in modified brain activity. Therefore, our study may contribute to the current understanding of human pain and will promote future research on this field.
    背景与目标:
  • 【偏头痛和早期异常性疼痛患者曲坦效果的差异。】 复制标题 收藏 收藏
    DOI:10.1111/j.1468-2982.2008.01642.x 复制DOI
    作者列表:Lampl C,Huber G,Haas S,Rittberger E,Diener HC
    BACKGROUND & AIMS: :The aim of this study was to determine whether in migraine patients with and without aura early treatment with various triptans leads to differences in pain reduction after 1 h and in modulating cutaneous allodynia. Thirty-six patients with early manifestation of a clinically recognizable allodynia of the face and non-responders to earlier treatment with sumatriptan 100 mg were included. Patients were randomized to six triptan treatment groups. Significant pain reduction was seen only in the group receiving zolmitriptan nasal spray 5 mg with a mean visual analogue scale (VAS) score of 3.8 (s.d. 1.2) at baseline and 2.4 (s.d. 1.3; P = 0.015) at 1 h after using the triptan and was thus a predictor of a VAS score 3 within 1 h. The study results indicate that migraine headache intensity can be reduced within 1 h by using zolmitriptan 5 mg nasal spray in spite of the presence of early cutaneous allodynia.
    背景与目标: : 这项研究的目的是确定在有和没有先兆的偏头痛患者中,使用各种曲坦药物进行早期治疗是否会导致1小时后疼痛减轻和调节皮肤异常性疼痛的差异。包括36例早期表现为临床可识别的面部异常性疼痛的患者和对舒马曲坦100 mg早期治疗无反应的患者。患者被随机分为六个曲普坦治疗组。仅在基线和2.4 (s.d. 1.3) 平均视觉模拟评分 (VAS) 为3.8 (s.d. 1.2) 的佐米曲普坦鼻喷雾剂5 mg组中观察到明显的疼痛减轻; P = 0.015) 在使用曲坦后1小时,因此是1小时内VAS评分3的预测因子。研究结果表明,尽管存在早期皮肤异常性疼痛,但使用佐米曲坦5 mg鼻喷雾剂可在1小时内降低偏头痛的强度。
  • 【月经相关偏头痛的异常性疼痛: 通过异常性疼痛症状清单 (ASC-12) 进行评分评估。】 复制标题 收藏 收藏
    DOI:10.1111/head.13677 复制DOI
    作者列表:Melhado EM,Thiers Rister HL,Galego DR,de Oliveira AB,Buttarello IA,Belucio IS,Oliveira Marcos JM,Xavier MLT,Peres MFP
    BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to compare the allodynia score in headache attacks related and not related to menstruation in women diagnosed with menstrually related migraine without aura. BACKGROUND:Allodynia is an important symptom in migraine and has been associated with migraine chronification. No study has yet compared prospectively allodynia in menstrual vs non-menstrual attacks within the same cohort of patients. METHODS:This is a prospective cohort study, where participants had the 12-item Allodynia Symptom Checklist (ASC-12) assessed after 1, 2, 4, and 24 hours from the onset of migraine attacks in 2 different conditions, with menstrual migraine attack (MM+) and with non-menstrual migraine attack (MM-). RESULTS:A total of 600 women with headache complaints were screened from March 2013 to July 2014 in a headache outpatient or headache tertiary clinic. From these, 55 participants were recruited, and 32 completed the study. Participants' mean age was 27 years, BMI was 22.1, menarche age 12 years, migraine history was 11.5 years, and most women were young (ranged from 17 to 44 years of age), were in higher school (13/32 = 41%), single (20/32 = 63%), and used contraceptives (22/32 = 69%). Multiple pairwise comparisons of ANCOVA's test showed significant higher ASC-12 scores in MM+ group compared to MM- group at 2 hours [mean, 95% CI of difference: 2.3 (0.31, 4.7), P = .049)]. For the ASC-12 categorical scores (absent, mild, moderate, and severe) MM+ yielded higher scores than MM- at 1 hour (z = -3.08, P = .021) and 4 hours (z = -2.97, P = .03). CONCLUSION:This study demonstrated that in the patents from tertiary headache center assessed, menstrual-related migraine attacks augment allodynia scores in the beginning of attacks compared to non-menstrual migraine attacks.
    背景与目标:
  • 【偏头痛中动态 (刷) 和静态 (压力) 机械异常性疼痛的比较。】 复制标题 收藏 收藏
    DOI:10.1111/j.1468-2982.2006.01121.x 复制DOI
    作者列表:LoPinto C,Young WB,Ashkenazi A
    BACKGROUND & AIMS: :Allodynia has been described in migraine but has not been fully investigated for the different sensory modalities. The aim of this study was to compare the prevalence of dynamic (brush) and static (pressure) mechanical allodynia in migraine patients and to suggest a practical method of testing them in a clinical setting. Patients with International Headache Society-defined episodic migraine (EM) or with transformed migraine (TM) as defined by Silberstein and Lipton were prospectively recruited from the Jefferson Headache Center out-patient clinic. A questionnaire of migraine features and symptoms of allodynia was administered. Brush allodynia (BA) was tested by cutaneous stimulation with a gauze pad and pressure allodynia (PA) was tested using von Frey hairs (VFH). The prevalence of BA and PA in all patients and in the different subgroups was calculated and correlated with migraine features. We recruited 55 migraine patients. Twenty-five had EM and 30 had TM. BA was present in 18 (32.7%) patients and PA in 18-24 (32.7-43.6%). Allodynia to both brush and pressure was found in 13-17 (23.6-30.9%) patients. If a patient had allodynia to one modality only, it was more likely to be PA than BA. Both BA and PA were more common in patients with TM compared with those with EM [BA 46.7% vs. 16.0%; PA (differences significant for the medium and thick VFHs) 50% vs. 20% and 50% vs. 12%, respectively]. Both types of allodynia were also more common in patients with migraine with aura compared with those with migraine without aura (BA 57.1% vs. 17.6%; PA 57.1-61.9% vs. 17.6-32.7%). There was a positive correlation between allodynia score (as obtained by examination) and allodynia index (as obtained by history) for both BA and PA. The incomplete, although considerable, overlap between BA and PA suggests that allodynia to different sensory modalities is associated with sensitization of different neuronal populations. Because PA was more common than BA, it may be a more sensitive indicator of allodynia in migraine. PA can be tested clinically in a practical and systematic manner.
    背景与目标: : 偏头痛中已经描述了异常性疼痛,但尚未对不同的感觉方式进行充分研究。这项研究的目的是比较偏头痛患者的动态 (刷) 和静态 (压力) 机械异常性疼痛的患病率,并提出一种在临床环境中进行测试的实用方法。前瞻性地从杰斐逊头痛中心门诊招募了国际头痛协会定义的发作性偏头痛 (EM) 或Silberstein和Lipton定义的转化偏头痛 (TM) 患者。进行了偏头痛特征和异常性疼痛症状的问卷调查。通过用纱布垫进行皮肤刺激来测试刷性异常性疼痛 (BA),并使用von Frey头发 (VFH) 测试压力异常性疼痛 (PA)。计算了所有患者和不同亚组中BA和PA的患病率,并将其与偏头痛特征相关联。我们招募了55名偏头痛患者。25个有EM,30个有TM。BA存在于18 (32.7%) 例患者中,PA存在于18-24 (32.7-43.6%) 中。在13-17 (23.6-30.9%) 例患者中发现了刷和压力的异常性疼痛。如果患者仅对一种方式有异常性疼痛,则PA比BA更有可能。与EM患者相比,TM患者中BA和PA更为常见 [BA 46.7% vs. 16.0%; PA (中等和厚VFHs的差异显着) 50% 分别为20% 和50% 与12%]。与无先兆偏头痛患者相比,两种类型的异常性疼痛在先兆偏头痛患者中也更常见 (BA 57.1% vs. 17.6%; PA 57.1-61.9% vs. 17.6-32.7%)。BA和PA的异常性疼痛评分 (通过检查获得) 与异常性疼痛指数 (通过病史获得) 之间呈正相关。BA和PA之间不完整 (尽管相当大) 的重叠表明,对不同感觉方式的异常性疼痛与不同神经元群体的敏化有关。由于PA比BA更常见,因此它可能是偏头痛异常性疼痛的更敏感指标。PA可以以实用和系统的方式进行临床测试。
  • 【神经性疼痛患者刷状诱发异常性疼痛的脑处理的fMRI研究。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroimage.2006.03.024 复制DOI
    作者列表:Schweinhardt P,Glynn C,Brooks J,McQuay H,Jack T,Chessell I,Bountra C,Tracey I
    BACKGROUND & AIMS: :Previous human imaging studies have revealed a network of brain regions involved in the processing of allodynic pain; this includes prefrontal areas, insula, cingulate cortex, primary and secondary somatosensory cortices and parietal association areas. In this study, the neural correlates of the perceived intensity of allodynic pain in neuropathic pain patients were investigated. In eight patients, dynamic mechanical allodynia was provoked and brain responses recorded using functional magnetic resonance imaging (fMRI). Voxels in which the magnitude of fMRI signal correlated linearly with the ratings of allodynic pain across the group were determined in a whole brain analysis using a general linear model. To ensure that activation reflected only allodynic pain ratings, a nuisance variable containing ratings of ongoing pain was included in the analysis. We found that the magnitude of activation in the caudal anterior insula (cAI) correlates with the perceived intensity of allodynic pain across subjects, independent of the level of ongoing pain. However, the peak of activation in the allodynic condition was located in the rostral portion (rAI). This matches the representation of other clinical pain syndromes, confirmed by a literature review. In contrast, experimental pain in healthy volunteers resides predominantly in the cAI, as shown by the same literature review. Taken together, our data and the literature review suggest a functional segregation of anterior insular cortex.
    背景与目标: : 先前的人类影像学研究揭示了参与异型疼痛处理的大脑区域网络; 这包括前额叶区域,岛叶,扣带回皮层,初级和次级体感皮层以及顶叶关联区域。在这项研究中,研究了神经性疼痛患者的异常性疼痛感知强度的神经相关性。在八名患者中,使用功能磁共振成像 (fMRI) 引起了动态机械性异常性疼痛,并记录了大脑反应。在使用一般线性模型的全脑分析中,确定了fMRI信号的大小与全组异常性疼痛的等级线性相关的体素。为了确保激活仅反映异常性疼痛等级,分析中包括了包含持续疼痛等级的滋扰变量。我们发现,尾部前岛岛 (cAI) 的激活程度与整个受试者的异常性疼痛的感知强度相关,而与持续疼痛的水平无关。然而,异常性状态下的激活峰值位于鼻尖部分 (rAI)。这与文献综述证实的其他临床疼痛综合征的表现相匹配。相反,如同一文献综述所示,健康志愿者的实验性疼痛主要发生在cAI中。综上所述,我们的数据和文献综述表明,前岛叶皮层具有功能性分离。
  • 【身体滥用通过神经源性炎症和spino-parabrachio-杏仁核途径激活,导致广泛的慢性机械痛觉过敏,触觉异常性疼痛和冷异常性疼痛。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2020-08-01
    来源期刊:Pain
    DOI:10.1097/j.pain.0000000000001867 复制DOI
    作者列表:Ohmichi Y,Ohmichi M,Tashima R,Osuka K,Fukushige K,Kanikowska D,Fukazawa Y,Yawo H,Tsuda M,Naito M,Nakano T
    BACKGROUND & AIMS: :Physical disuse could lead to a state of chronic pain typified by complex regional pain syndrome type I due to fear of pain through movement (kinesiophobia) or inappropriate resting procedures. However, the mechanisms by which physical disuse is associated with acute/chronic pain and other pathological signs remain unresolved. We have previously reported that inflammatory signs, contractures, disuse muscle atrophy, spontaneous pain-like behaviors, and chronic widespread mechanical hyperalgesia based on central plasticity occurred after 2 weeks of cast immobilization in chronic post-cast pain (CPCP) rat model. In this study, we also demonstrated dystrophy-like changes, both peripheral nociceptive signals and activation of the central pain pathway in CPCP rats. This was done by the following methods: (1) vascular permeability (Evans blue dye) and inflammatory- and oxidative stress-related messenger RNA changes (real-time quantitative polymerase chain reaction); (2) immunofluorescence of pERK and/or c-Fos expression in the spino-parabrachio-amygdaloid pathway; and (3) blockade of nociceptive-related signals using sciatic nerve block. Furthermore, we demonstrated tactile allodynia using an optogenetic method in a transgenic rat line (W-TChR2V4), cold allodynia using the acetone test, and activation of dorsal horn neurons in the chronic phase associated with chronic mechanical hyperalgesia using c-Fos immunofluorescence. In addition, we showed that nociceptive signals in the acute phase are involved in chronic pathological pain-like behaviors by studying the effects of sciatic nerve block. Thus, we conclude that physical disuse contributes to dystrophy-like changes, spontaneous pain-like behavior, and chronic widespread pathological pain-like behaviors in CPCP rats after 2 weeks of cast immobilization.
    背景与目标: : 由于害怕通过运动 (运动恐惧症) 或不适当的休息程序而引起的疼痛,身体上的不使用可能导致以I型复杂区域疼痛综合征为代表的慢性疼痛状态。然而,身体使用与急/慢性疼痛和其他病理体征相关的机制仍未解决。我们以前曾报道,在慢性铸后疼痛 (CPCP) 大鼠模型中,在石膏固定2周后发生了炎症体征,挛缩,废用肌肉萎缩,自发性疼痛样行为和基于中枢可塑性的慢性广泛的机械痛觉过敏。在这项研究中,我们还证明了CPCP大鼠的营养不良样变化,包括外周伤害感受信号和中枢疼痛途径的激活。这是通过以下方法完成的 :( 1) 血管通透性 (伊文思蓝染料) 和炎症和氧化应激相关的信使RNA变化 (实时定量聚合酶链反应); (2) spino-parabrachio-杏仁核途径中pERK和/或c-Fos表达的免疫荧光; (3) 使用坐骨神经阻滞阻断伤害性相关信号。此外,我们在转基因大鼠品系 (W-TChR2V4) 中使用光遗传学方法证明了触觉异常性疼痛,使用丙酮测试证明了冷异常性疼痛,以及使用c-Fos免疫荧光激活与慢性机械痛觉过敏相关的慢性期背角神经元。此外,通过研究坐骨神经阻滞的作用,我们发现急性期的伤害性信号与慢性病理性疼痛样行为有关。因此,我们得出的结论是,石膏固定2周后,CPCP大鼠的身体使用会导致营养不良样变化,自发性疼痛样行为和慢性广泛的病理性疼痛样行为。
  • 【抗肿瘤坏死因子-α 的抗体可减少硼替佐米诱导的大鼠模型中的异常性疼痛。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Chiorazzi A,Canta A,Meregalli C,Carozzi V,Sala B,Oggioni N,Monbaliu J,VAN DE Velde H,Cavaletti G
    BACKGROUND & AIMS: BACKGROUND:Bortezomib is an anti-neoplastic drug acting against multiple myeloma but its use is associated with the onset of painful peripheral neuropathy. Tumor necrosis factor-α (TNFα) is associated with the development of neuropathic pain; several models have shown that the inactivation of TNFα leads to a reduction in pain stimuli perception. The aim of the present study was to analyze if the administration of an antibody against TNFα is able to prevent the development of bortezomib-induced neuropathic pain. MATERIALS AND METHODS:Nerve conduction velocity was measured and a histopathological examination was performed to assess the extent of peripheral neuropathy. To study the onset of painful neuropathy, the response to mechanical or thermal stimuli was evaluated. RESULTS:This study demonstrated that co-administration of an antibody against TNFα is able to prevent allodynia induced by bortezomib but does not reduce neuropathy. CONCLUSION:Targeting TNFα might be useful in limiting patients' discomfort during bortezomib therapy.
    背景与目标:
  • 【大鼠短暂性颈神经根受压可引起双侧前爪异常性疼痛和脊髓神经胶质激活: 颈部疼痛的机械因素。】 复制标题 收藏 收藏
    DOI:10.1097/01.brs.0000176239.72928.00 复制DOI
    作者列表:Hubbard RD,Winkelstein BA
    BACKGROUND & AIMS: STUDY DESIGN:An in vivo rat model of transient cervical nerve root compression. OBJECTIVES:To investigate the potential for cervical nerve root compression to produce behavioral hypersensitivity and examine its dependence on compression. SUMMARY OF BACKGROUND DATA:Clinically, nerve root injury has been hypothesized as a potential source of neck pain, particularly because cervical nerve roots are at mechanical risk for injury during neck loading. Lumbar radiculopathy models of nerve root ligation show that mechanical allodynia and spinal glial changes depend on nerve root deformation magnitude. However, no investigation has been performed to examine cervical nerve root compression as a cause of pain. METHODS:Two compressive forces (10 and 60 grams force [gf]) were transiently applied to the C7 nerve roots unilaterally using microvascular clips in separate groups (n = 12 each). Sham procedures were also performed in a separate group of rats (n = 12). Bilateral forepaw mechanical allodynia was monitored after surgery for 7 days. On day 7, spinal glial activation was assessed using immunohistochemistry to investigate its dependence on nerve root compressive force, in the context of behavioral hypersensitivity. RESULTS:Bilateral allodynia was observed following injury, which was significantly (P < 0.042) increased over sham and baseline responses. No difference in allodynia was found between the 10 and 60 gf injuries. Astrocytic and microglial activation were observed in the ipsilateral dorsal horn following compression, with only astrocytic activation paralleling allodynia patterns. CONCLUSIONS:Results imply a force threshold exists less than 10 gf for persistent pain symptoms following transient cervical nerve root compression. Findings also suggest that spinal glial activation may be related to behavioral sensitivity and may modulate cervical nerve root mediated pain.
    背景与目标:
  • 【鞘内注射前列腺素f2α 引起的异常性疼痛。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:1992-08-01
    来源期刊:Pain
    DOI:10.1016/0304-3959(92)90166-9 复制DOI
    作者列表:Minami T,Uda R,Horiguchi S,Ito S,Hyodo M,Hayaishi O
    BACKGROUND & AIMS: :The intrathecal administration of prostaglandin F2 alpha to conscious mice resulted in spontaneous agitation and touch-evoked agitation (allodynia) in the animals. The maximum allodynia induced by prostaglandin F2 alpha was observed at 10-15 min after intrathecal injection, and the response did not disappear by 120 min. Prostaglandin F2 alpha produced allodynia over a wide range of dosage from 0.1 pg to 2.5 micrograms/mouse. Dose dependency of prostaglandin F2 alpha for allodynia showed a skewed bell-shaped pattern, and the maximal allodynic effect was observed at 1.0 microgram. This allodynia was dose-dependently relieved by alpha 1-adrenergic (methoxamine), alpha 2-adrenergic (clonidine), and A1-adenosine (RPIA) agonists. Clonidine was 1.5 orders of magnitude more potent than methoxamine in blocking prostaglandin F2 alpha-induced allodynia. The blockade by clonidine was dose-dependently reversed by the alpha 2-adrenergic antagonist yohimbine but not by the alpha 1-adrenergic antagonist prazosin. These results demonstrate that prostaglandin F2 alpha administered intrathecally induces allodynia in conscious mice and that the allodynia involves the alpha 2-adrenergic and A1-adenosine systems. Because this allodynia has a clear resemblance to the characteristics of chronic pain in patients with causalgia and reflex sympathetic dystrophy, prostaglandin F2 alpha may be involved in allodynia observed with these disorders.
    背景与目标: : 鞘内给予有意识的小鼠前列腺素f2α 会导致动物自发的躁动和触摸诱发的躁动 (异常性疼痛)。鞘内注射后10-15分钟观察到前列腺素f2α 诱导的最大异常性疼痛,120分钟后反应没有消失。前列腺素f2α 在从0.1微克到2.5微克/小鼠的宽剂量范围内产生异常性疼痛。前列腺素f2α 对异常性疼痛的剂量依赖性显示出倾斜的钟形模式,并且在1.0微克处观察到最大的异常性疼痛作用。通过 α1-肾上腺素能 (甲氧胺),α2-肾上腺素能 (可乐定) 和A1-adenosine (RPIA) 激动剂剂量依赖性地缓解了这种异常性疼痛。可乐定在阻断前列腺素f2α 诱导的异常性疼痛方面比甲氧胺强1.5个数量级。可乐定的阻滞剂被 α2-肾上腺素能拮抗剂育亨宾以剂量依赖性逆转,但不能被 α1-肾上腺素能拮抗剂哌唑嗪逆转。这些结果表明,鞘内给药的前列腺素f2α 在有意识的小鼠中诱导异常性疼痛,并且异常性疼痛涉及 α2-肾上腺素能和A1-adenosine系统。由于这种异常性疼痛与慢性疼痛和反射性交感神经营养不良患者的特征明显相似,因此前列腺素f2α 可能与这些疾病的异常性疼痛有关。
  • 【米诺环素减轻疼痛促进大鼠模型中的机械性异常性疼痛和促炎细胞因子表达。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2005-05-01
    来源期刊:Pain
    DOI:10.1016/j.pain.2005.02.009 复制DOI
    作者列表:Ledeboer A,Sloane EM,Milligan ED,Frank MG,Mahony JH,Maier SF,Watkins LR
    BACKGROUND & AIMS: :Activated glial cells (microglia and astroglia) in the spinal cord play a major role in mediating enhanced pain states by releasing proinflammatory cytokines and other substances thought to facilitate pain transmission. In the present study, we report that intrathecal administration of minocycline, a selective inhibitor of microglial cell activation, inhibits low threshold mechanical allodynia, as measured by the von Frey test, in two models of pain facilitation. In a rat model of neuropathic pain induced by sciatic nerve inflammation (sciatic inflammatory neuropathy, SIN), minocycline delayed the induction of allodynia in both acute and persistent paradigms. Moreover, minocycline was able to attenuate established SIN-induced allodynia 1 day, but not 1 week later, suggesting a limited role of microglial activation in more perseverative pain states. Our data are consistent with a crucial role for microglial cells in initiating, rather than maintaining, enhanced pain responses. In a model of spinal immune activation by intrathecal HIV-1 gp120, we show that the anti-allodynic effects of minocycline are associated with decreased microglial activation, attenuated mRNA expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-1beta-converting enzyme, TNF-alpha-converting enzyme, IL-1 receptor antagonist and IL-10 in lumbar dorsal spinal cord, and reduced IL-1beta and TNF-alpha levels in the CSF. In contrast, no significant effects of minocycline were observed on gp120-induced IL-6 and cyclooxygenase-2 expression in spinal cord or CSF IL-6 levels. Taken together these data highlight the importance of microglial activation in the development of exaggerated pain states.
    背景与目标: : 脊髓中活化的神经胶质细胞 (小胶质细胞和星形胶质细胞) 通过释放促炎细胞因子和其他被认为有助于疼痛传递的物质,在介导增强的疼痛状态中起主要作用。在本研究中,我们报告在两种疼痛促进模型中,鞘内施用米诺环素 (一种小胶质细胞活化的选择性抑制剂) 可抑制低阈值机械性异常性疼痛,这是通过von Frey测试测得的。在由坐骨神经炎症 (坐骨神经炎性神经病,SIN) 引起的神经性疼痛的大鼠模型中,米诺环素在急性和持续性范例中均延迟了异常性疼痛的诱导。此外,米诺环素能够减轻SIN诱导的异常性疼痛1天,但不能在1周后减弱,这表明小胶质细胞激活在更持续的疼痛状态中的作用有限。我们的数据与小胶质细胞在启动而不是维持增强的疼痛反应中的关键作用一致。在鞘内HIV-1 gp120激活脊髓免疫模型中,我们发现米诺环素的抗异常性作用与减少小胶质细胞活化,减弱interleukin-1beta (IL-1beta),肿瘤坏死因子-α (TNF-α),IL-1beta-converting酶,TNF-α 转化酶,IL-1受体拮抗剂和IL-10在腰背脊髓中,并降低CSF中的IL-1beta和TNF-α 水平。相反,没有观察到米诺环素对脊髓或CSF IL-6水平的gp120-induced IL-6和cyclooxygenase-2表达的显着影响。综合起来,这些数据突出了小胶质细胞激活在过度疼痛状态发展中的重要性。
  • 【Δ 阿片受体对于三环抗抑郁药治疗神经性异常性疼痛至关重要。】 复制标题 收藏 收藏
    DOI:10.1016/j.biopsych.2007.06.016 复制DOI
    作者列表:Benbouzid M,Gavériaux-Ruff C,Yalcin I,Waltisperger E,Tessier LH,Muller A,Kieffer BL,Freund-Mercier MJ,Barrot M
    BACKGROUND & AIMS: BACKGROUND:The therapeutic effect of antidepressant drugs against depression usually necessitates a chronic treatment. A large body of clinical evidence indicates that antidepressant drugs can also be highly effective against chronic neuropathic pain. However, the mechanism by which these drugs alleviate pain is still unclear. METHODS:We used a murine model of neuropathic pain induced by sciatic nerve constriction to study the antiallodynic properties of a chronic treatment with the tricyclic antidepressants nortriptyline and amitriptyline. Using knockout and pharmacological approaches in mice, we determined the influence of delta-opioid receptors in the therapeutic action of chronic antidepressant treatment. RESULTS:In our model, a chronic treatment by tricyclic antidepressant drugs totally suppresses the mechanical allodynia in neuropathic C57Bl/6J mice. This therapeutic effect can be acutely reversed by an injection of the delta-opioid receptor antagonist naltrindole. Moreover, the antiallodynic property of antidepressant treatment is absent in mice deficient for the delta-opioid receptor gene. CONCLUSIONS:The antiallodynic effect of chronic antidepressant treatment is mediated by a recruitment of the endogenous opioid system acting through delta-opioid receptors.
    背景与目标:
  • 【通过p物质旁分泌机制激活三叉根神经节的NK1受体有助于大鼠颞下颌关节炎症中的机械性异常性疼痛。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2005-08-01
    来源期刊:Pain
    DOI:10.1016/j.pain.2005.05.007 复制DOI
    作者列表:Takeda M,Tanimoto T,Nasu M,Ikeda M,Kadoi J,Matsumoto S
    BACKGROUND & AIMS: :The aim of this study was to investigate whether under in vivo conditions, temporomandibular joint (TMJ) inflammation alters the excitability of Abeta-trigeminal root ganglion (TRG) neuronal activity innervating the facial skin by using extracellular electrophysiological recording with multibarrel-electrodes. Complete Freund's adjuvant (CFA) was injected into the rat TMJ. Threshold for escape from mechanical stimulation applied to the whisker pad area in inflamed rats (2 days) was significantly lower than that in control rats. A total of 36 Abeta-TRG neurons responding to electrical stimulation of the whisker pad was recorded in pentobarbital-anesthetized rats. The number of Abeta-TRG neurons with spontaneous firings and their firing rate in TMJ inflamed rats were significantly larger than those in control rats. The firing rates of their spontaneous activity in the Abeta-TRG neurons were current-dependently decreased by local iontophoretic application of an NK1 receptor antagonist (L-703,606) in inflamed, but not non-inflamed rats. Their spontaneous activities were current-dependently increased by local iontophoretic application of substance P (SP) in control and inflamed rats. The mechanical response threshold of Abeta-TRG neurons in inflamed rats was significantly lower than that in control rats. The mechanical response threshold in inflamed rats after iontophoretic application of L-703,606 was not different from that in control rats. These results suggest that TMJ inflammation modulate the excitability of Abeta-TRG neurons innervating the facial skin via paracrine mechanism due to SP released from TRG neuronal cell body. Such a SP release may play an important role in determining the trigeminal inflammatory allodynia concerning the temporomandibular disorder.
    背景与目标: : 这项研究的目的是研究在体内条件下,颞下颌关节 (TMJ) 炎症是否通过使用多桶电极的细胞外电生理记录来改变支配面部皮肤的 β-三叉神经节 (TRG) 神经元活动的兴奋性。将完整的弗氏佐剂 (CFA) 注射到大鼠TMJ中。在发炎的大鼠 (2天) 中,从施加到晶须垫区域的机械刺激中逃脱的阈值显着低于对照大鼠。在戊巴比妥麻醉的大鼠中,总共记录了36个对晶须垫电刺激有反应的Abeta-TRG神经元。TMJ发炎大鼠自发放电的Abeta-TRG神经元数量及其放电速率明显大于对照组。在发炎但非发炎的大鼠中,通过局部离子电渗应用NK1受体拮抗剂 (L-703,606),电流依赖性地降低了它们在Abeta-TRG神经元中的自发活动的放电速率。通过在对照和发炎的大鼠中局部离子电渗施用p物质 (SP),它们的自发活动随电流而增加。炎症大鼠的Abeta-TRG神经元的机械反应阈值明显低于对照组。L-703,606离子电渗后发炎大鼠的机械反应阈值与对照大鼠没有差异。这些结果表明,由于TRG神经元细胞体释放的SP,TMJ炎症通过旁分泌机制调节了支配面部皮肤的Abeta-TRG神经元的兴奋性。这种SP释放可能在确定与颞下颌疾病有关的三叉神经炎性异常性疼痛中起重要作用。
  • 【严重的胸部异常性疼痛是包虫病的不寻常首发表现: 一例报告。】 复制标题 收藏 收藏
    DOI:10.1186/s12879-019-3670-7 复制DOI
    作者列表:Coluzzi F,Meniconi RL,Caruso D,Rivosecchi F,Petrone L,Goletti D,Ettorre GM
    BACKGROUND & AIMS: BACKGROUND:Cystic echinococcosis (CE) is a worldwide zoonosis and the liver is the most commonly affected organ. Clinical manifestations range from completely asymptomatic cysts to a potential lethal cyst rupture and anaphylaxis. CASE PRESENTATION:Severe chest allodynia was an unusual clinical presentation of hepatic cyst rupture in the retroperitoneal space, without any other specific symptoms. CE diagnosis was confirmed by computed tomography scan and magnetic resonance. The patient underwent hepatectomy with complete resolution of the neuropathic pain. CONCLUSIONS:Retroperitoneal hydatid cyst rupture is a rare event and its clinical manifestation may mimic other chest neuropathies.
    背景与目标:

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