创伤性脊髓损伤患者神经病理性疼痛的影响因素及临床特点：回顾性研究

摘要目的：分析脊髓损伤（spinal cord injury,SCI）患者神经病理性疼痛（neuropathic pain,NPP）的影响因素及临床特点。方法：对2018年10月—2019年6月从西南医科大学附属医院康复科和四川省绵竹市人民医院康复科出院的SCI患者,进行国际脊髓损伤疼痛数据集调查并分析。结果：共纳入96例SCI患者,54.2%（52/96）患者出现NPP。多因素Logistic回归分析,性别、年龄、ASIA分级、距离受伤的时间、伤害感受性疼痛与患者是否出现NPP有关（P<0.05）。其中,影响因素前3位分别是伤害感受性疼痛、性别和距离损伤的时间。52位NPP患者中,82.7%（43/52）合并有伤害感受性疼痛。NPP患者平均NRS评分为6.4±2.0,61.5%（32/52）患者1周中每天都会出现疼痛,30.8%（16/52）患者疼痛为持续性,55.8%（29/52）患者疼痛最明显的时间不可预测,疼痛对患者日常生活、活动、情绪、睡眠等产生中度以上的影响及干扰。59.6%（31/52）患者未接受疼痛相关的任何治疗。结论：伤害感受性疼痛、性别、损伤时间、年龄、ASIA分级与SCI患者是否发生NPP有关。患者平均疼痛强度为中重度,大部分患者每天都会经历疼痛,疼痛最明显的时间不可预测,约1/3患者疼痛为持续性,NPP产生的干扰及影响为中重度。大部分SCI患者未接受规范的NPP相关的治疗。     

脊髓损伤患者神经病理性疼痛经历的质性研究

目的了解脊髓损伤患者继发神经病理性疼痛的经历,为制订有效的镇痛方案奠定基础。方法采用现象学研究方法对6例脊髓损伤继发神经病理性疼痛的患者进行半结构式访谈,用Colaizzi分析法分析脊髓损伤继发神经病理性疼痛患者的疼痛经历。结果脊髓损伤继发神经病理性疼痛患者的疼痛经历分为3个主题:不确定的疼痛体验、疼痛情感错综复杂和重拾信心应对疼痛。结论脊髓损伤继发神经病理性疼痛不同于一般的慢性疼痛,其是一种顽固且不确定的疼痛。目前医护人员对脊髓损伤继发神经病理性疼痛缺乏规范与系统的管理,尤其是护理人员缺乏相关的专业知识;而患者对疼痛的正面应对方式也需要正确指导。     

普瑞巴林联合神经妥乐平治疗脊髓损伤患者神经病理性疼痛的疗效观察

目的:探讨神经妥乐平对于脊髓损伤后神经病理性疼痛的临床疗效,同时比较单独使用神经妥乐平与联合使用普瑞巴林和神经妥乐平对神经病理性疼痛的缓解程度、对患者情绪以及睡眠状况的改善情况。方法:选取符合入组标准的脊髓损伤伴神经病理性疼痛患者62例,电脑随机分2组,分别为神经妥乐平组、普瑞巴林联合神经妥乐平组,神经妥乐平组起始剂量为4U bid,普瑞巴林联合神经妥乐平组起始剂量为普瑞巴林75mg bid+神经妥乐平4U bid,间隔3d调整药物剂量,疗程为4周。采用视觉模拟评分量表(visual analogue scale,VAS)、医院焦虑抑郁量表(hospital anxiety and depression scale,HAD)、匹茨堡睡眠质量指数量表(Pittsburgh sleep quality index,PSQI)对患者进行疼痛、情绪和睡眠质量的评估。由专业的康复治疗师对患者服药前和疗程结束后的疗效分别进行评估。结果:单独使用神经妥乐平可以缓解脊髓损伤患者神经病理性疼痛,同时改善患者睡眠质量,治疗前后比较差异有显著性意义(P0.05);而联合使用普瑞巴林和神经妥乐平治疗后,患者的VAS和HAD评分均较神经妥乐平组明显降低,差异有显著性意义(P0.05)。结论:神经妥乐平可以缓解脊髓损伤患者的疼痛症状,联合使用普瑞巴林和神经妥乐平不仅明显缓解脊髓损伤神经病理性疼痛患者的疼痛症状,同时显著改善了患者的焦虑抑郁情绪,提高患者睡眠质量,进而提升患者生存质量,是一种有效的临床治疗方法。     

重复经颅磁刺激改善脊髓损伤患者神经病理性疼痛疗效的系统评价

目的:系统评价重复经颅磁刺激治疗脊髓损伤患者神经病理性疼痛的疗效。方法:计算机检索MEDLINE、Embase、Cochrane Library、ISI、维普数据库、万方数据库和中国知网数据库从建库至2018年1月研究重复经颅磁刺激治疗脊髓损伤患者神经病理性疼痛的随机对照试验。由2位研究者按照纳入标准和排除标准筛选文献...     

伴发神经病理性疼痛的脊髓损伤患者脑电生物标记分析

摘要 目的：定量评价伴有神经病理性疼痛的脊髓损伤（spinal cord injury, SCI）患者在静息和执行运动想象任务时脑电信号的特征,识别脑电生物标记。 方法：选取2020年6月—2021年12月在山东大学齐鲁医院住院治疗的SCI患者,采用利兹神经病理性症状和体征评分（Leeds assessment of neuropathic symptoms and signs, LANSS）评定患者的疼痛程度,分为有疼痛的PWP（the patients with pain）组,无疼痛的PNP（the patients without pain）组,健康人作为AB对照组（均n=9）。记录受试者静息态左手、右手和双脚运动想象任务态脑电信号。通过改进的S变换,分别计算出θ（4—8Hz）、α（8—12Hz）与β（13—30Hz）频带的功率谱密度（power spectra density, PSD）和θ/α值。比较3组患者脑电信号特征,计算与LANSS评分的相关性。 结果：在睁眼静息状态下,PWP组多个信道的θ/α值明显高于PNP组与AB组（均P<0.05）。运动想象时,PNP组多个信道的α和β频带PSD值明显高于PWP组和AB组（均P<0.05）;在静息状态下及运动想象时,疼痛患者多个信道α、θ频带PSD值和θ/α值与疼痛评分有相关性（均P<0.05）。 结论：脑电图的θ/α值可作为SCI后神经病理性疼痛的生物标记,且可作为疼痛严重程度的评价指标。     

脊髓电刺激对神经病理性疼痛镇痛作用及相关机制研究

目的:探索脊髓电刺激(spinal cord stimulation, SCS)对小鼠神经病理性疼痛的镇痛作用并阐明相关机制。方法:30只健康成年雄性野生型CD1小鼠随机分为对照组(Sham)、坐骨神经结扎损伤组(chronic constriction injury, CCI)和治疗组(CCI+SCS),每组10只。通过行为学观察SCS对外周神经损伤引起的机械痛敏和热痛敏的缓解情况,以及对小鼠运动功能影响程度;采用电生理方法记录各组小鼠背根神经节(dorsal root ganglion, DRG)中小神经元的兴奋性;通过酶联免疫吸附试验测定DRG内炎性因子TNF-α的表达水平。结果:与对照组比较,CCI组小鼠机械痛阈值和热痛阈值明显降低(P <0.05)。治疗组与CCI造模组比较,SCS可提高小鼠的机械痛和热痛阈值。同时,各组转棒实验评分无差异。电生理及酶联免疫吸附试验结果提示外周神经损伤后,同侧小鼠背根神经节(dorsal root ganglion, DRG)神经元的兴奋性增强,同时DRG内TNF-α的释放增加,治疗组与CCI组比较,SCS可以明显抑制DRG神经元的兴奋性增强(P <0.05)和DRG内TNF-α的释放增加(P <0.05)。结论:SCS通过抑制外周神经损伤导致的DRG神经元的兴奋性增强,从而有效地减缓小鼠CCI导致的机械感觉过敏和热痛敏,并可减少CCI小鼠DRG中TNF-α的表达水平。     

氯胺酮对神经病理性疼痛脊髓背角生长相关蛋白表达的影响

目的：观察氯胺酮对脊神经结扎大鼠脊髓背角生长相关蛋白-43（GAP-43）表达的影响。方法：25只雄性S D大鼠,随机分成5组;假手术组,氯胺酮Ⅰ、Ⅱ、Ⅲ组,生理盐水组。行为学上应用von Frey Hair测定上述各组机械缩足时间变化（n=5）,采用免疫组织化学方法测定脊髓背角GAP-43表达的变化（n=5）。结果：氯胺酮组和生理盐水组,1周后均形成神经病理性疼痛模型。腹腔注射不同剂量氯胺酮均可逆转机械性痛觉过敏,氯胺酮组机械缩足时间与生理盐水组比较有显著统计学意义（P（0.001）。各组GAP-43表达随氯胺酮药物浓度增大而含量增加,生理盐水组亦可见GAP-43表达。结论：GAP-43可以阻断神经病理性疼痛中枢敏化的形成,氯胺酮能在很大程度上增强GAP-43的表达,从而起到治疗神经病理性疼痛的作用。     

脊髓损伤后神经病理性疼痛机制的研究进展

脊髓损伤(spinal cord injury,SCI)对患者造成严重心理伤害,对家庭造成沉重经济负担,并对社会造成巨大劳动力损失。SCI后神经重塑对神经功能的恢复至关重要,但其可能促进神经病理性疼痛(neuropathic pain,NP)的产生,NP通常有两个突出的症状:异常性疼痛(本身存在自发性疼痛并由通常不会引起疼痛的刺激诱发疼痛加重)和痛觉过敏(通常引起疼痛的刺激引起的疼痛增加)[1],50%~60%的SCI患者产生了相关症状[2],推高了医疗保健费用[3]。     

脊髓损伤患者并发神经病理性疼痛危险因素的回顾性研究

目的:研究脊髓损伤患者并发神经病理性疼痛(NP)的相关危险因素。方法:回顾性分析2018年1月至2021年12月由空军军医大学第一附属医院康复医学科收治的脊髓损伤患者115例。按病程中是否出现NP,分为NP组(53例)和非NP组(62例)。统计两组患者入院时的性别、年龄、病程、职业、教育程度、发病原因、脊柱骨折情况、脊...     

脊髓电刺激治疗神经病理性疼痛的临床现状及进展

多数学者认为慢性疼痛已构成一种单独疾病的病理生理过程,而其中神经病理性疼痛因对传统药物、物理等治疗不敏感而成为长期困扰患者的顽疾。目前对神经病理性疼痛的治疗有了突飞猛进的进展,新的治疗手段也正在不断应用于临床。本文回顾了近几年有关脊髓电刺激治疗神经病理性疼痛的国内外文献,希望能为临床工作提供参考。     

Referred sensations and neuropathic pain following spinal cord injury

It has been proposed that painful and non-painful referred sensations (RSs) are associated with reorganization of sensory pathways in patients with complete spinal cord injury (SCI). In order to investigate the referred sensation (RS) phenomenon and its correlation with neuropathic pain (NP) 48 patients with complete SCI, 24 with chronic NP and 24 without pain or paraesthesias were studied using clinical examination and neurophysiological tests. Patients reporting RSs were re-examined at 2 and 10 weeks after the first examination. We defined the presence of RS as sensations perceived below the injury level in response to touch and pinprick stimuli in various body points above the injury level. The examination was carried out by one researcher applying the stimuli to the patient under two visual conditions (open and closed eyes), and then asking the patient to make tactile self-stimulation. Seven patients with SCI and NP (29%) reported RS below the injury level. RS were well located and consistently evoked at repeated examinations. Touch and pinprick stimulation elicited similar RS that were non-painful in six patients and painful in one. Visual feedback did not change RS perception and characteristics. None of the patients in the SCI group without NP presented RS. In conclusion, our results indicate that RS is relatively frequent in patients with complete SCI and NP. The common occurrence of RS in patients with NP and the location of the sensations in the same area as NP suggest that pain and RS share common pathophysiological mechanisms.     

Functional MRI of the brain detects neuropathic pain in experimental spinal cord injury

Functional magnetic resonance imaging (fMRI) has been used to map cerebral activations related to nociceptive stimuli in rodents. Here, we used fMRI to investigate abnormally increased responses to noxious or innocuous stimuli, in a well-established rat model of chronic neuropathic pain induced by photochemical lumbar spinal cord injury. In this model, a subpopulation of rats exhibits allodynia-like hypersensitivity to mechanical and cold stimulation of the trunk area. In those rats that do not develop overt hypersensitivity after identical spinal cord injury (i.e. non-hypersensitive rats), touch evoked pain can be triggered by the opioid receptor antagonist, naloxone. We show that cerebral activations in contralateral primary somatosensory cortex (SI) are markedly correlated with different behavioural characteristics of these animals. Identical electrical stimulation, applied on trunks of spinally injured hypersensitive and non-hypersensitive rats, evoked significantly higher responses in SI of the former than the latter. Although levels of fMRI signals in SI of the trunk territory were not significantly different between normal and spinally injured non-hypersensitive rats, the administration of naloxone significantly increased fMRI signals in the non-hypersensitive rats, but not in the normal rats. We conclude that increased activation of contralateral SI is a key feature of behavioural neuropathic pain in spinally injured rats and that fMRI is an effective method to monitor experimental neuropathic pain in small animals.     

Virtual reality for spinal cord injury-associated neuropathic pain: Systematic review

Background

Treatment of spinal cord injury (SCI)-associated neuropathic pain is challenging, with limited efficacy and no definitive options, and SCI patients often show resistance to pharmacologic treatment. Virtual reality (VR) therapy is a non-invasive, non-pharmacologic alternative with minimal adverse effects.

Thalamic activity and biochemical changes in individuals with neuropathic pain after spinal cord injury

There is increasing evidence relating thalamic changes to the generation and/or maintenance of neuropathic pain. We have recently reported that neuropathic orofacial pain is associated with altered thalamic anatomy, biochemistry, and activity, which may result in disturbed thalamocortical oscillatory circuits. Despite this evidence, it is possible that these thalamic changes are not responsible for the presence of pain per se, but result as a consequence of the injury. To clarify this subject, we compared brain activity and biochemistry in 12 people with below-level neuropathic pain after complete thoracic spinal cord injury with 11 people with similar injuries and no neuropathic pain and 21 age- and gender-matched healthy control subjects. Quantitative arterial spinal labelling was used to measure thalamic activity, and magnetic resonance spectroscopy was used to determine changes in neuronal variability quantifying N-acetylaspartate and alterations in inhibitory function quantifying gamma amino butyric acid. This study revealed that the presence of neuropathic pain is associated with significant changes in thalamic biochemistry and neuronal activity. More specifically, the presence of neuropathic pain after spinal cord injury is associated with significant reductions in thalamic N-acetylaspartate, gamma amino butyric acid content, and blood flow in the region of the thalamic reticular nucleus. Spinal cord injury on its own did not account for these changes. These findings support the hypothesis that neuropathic pain is associated with altered thalamic structure and function, which may disturb central processing and play a key role in the experience of neuropathic pain.     

Movement imagery increases pain in people with neuropathic pain following complete thoracic spinal cord injury

Spinal cord injury (SCI) results in deafferentation and the onset of neuropathic pain in a substantial proportion of people. Based on evidence suggesting motor cortex activation results in attenuation of neuropathic pain, we sought to determine whether neuropathic SCI pain could be modified by imagined movements of the foot. Fifteen subjects with a complete thoracic SCI (7 with below-level neuropathic pain and 8 without pain) were instructed in the use of movement imagery. Movement imagery was practiced three times daily for 7days. On the eighth day, subjects performed the movement imagery in the laboratory and recorded pain ratings during the period of imagined movement. Six out of 7 subjects with neuropathic pain reported an increase in pain during imagined movements from 2.9+/-0.7 during baseline to 5.0+/-1.0 during movement imagery (p<0.01). In SCI subjects without neuropathic pain, movement imagery evoked an increase in non-painful sensation intensity from a baseline of 1.9+/-0.7 to 4.8+/-1.3 during the movement imagery (p<0.01). Two subjects without a history of pain or non-painful phantom sensations had onset of dysesthesia while performing imagined movements. This study reports exacerbation of pain in response to imagined movements and it contrasts with reports of pain reduction in people with peripheral neuropathic pain. The potential mechanisms underlying this sensory enhancement with movement imagery are discussed.     

重复经颅磁刺激联合针刺治疗脊髓损伤后神经病理性疼痛的临床研究

目的：观察重复经颅磁刺激（rTMS）联合针刺治疗脊髓损伤（SCI）后神经病理性疼痛（NP）的临床疗效。方法：按随机数字表法将99例SCI后NP患者分成对照组、针刺组和联合组,各33例。对照组进行常规基础治疗,针刺组在对照组基础上进行针刺治疗,联合组在针刺组基础上进行rTMS治疗。分别于治疗前及治疗6周后对3组患者进行视觉模拟量表（VAS）、汉密顿抑郁量表（HAMD）、汉密顿焦虑量表(HAMA)及生活质量SF-36量表评估。结果：治疗6周后,3组患者VAS、HAMD和HAMA评分较治疗前均明显降低（P＜0.05）,SF-36量表各项评分较治疗前均明显升高（P＜0.05）;针刺组VAS、HAMD和HAMA评分较对照组均有降低（P＜0.05）,SF-36量表各项评分较对照组均有升高（P＜0.05）;联合组VAS、HAMD和HAMA评分较针刺组和对照组均有降低（P＜0.05）,SF-36量表各项评分较针刺组和对照组均有升高（P＜0.05）。结论：rTMS联合针刺治疗SCI后NP患者,有助于改善患者临床疼痛现象,且在改善患者情绪和生活质量方面疗效显著。     

Combined approaches for the relief of spinal cord injury-induced neuropathic pain

The adequate treatment of spinal cord injury (SCI)-induced neuropathic pain still remains an unresolved problem. The current medications predominantly used in the SCI-induced neuropathic pain therapy are morphine, anticonvulsants, antidepressants, and antiepileptics, which suggests that psychiatric aspects might be important factors in the treatment of neuropathic pain.It is well documented that the modulation of the sensory events is not a unique way for achieving pain relief. In addition, pain patients still express dissatisfaction and complain of unwanted effects of the medications, suggesting that alternative approaches for the treatment of neuropathic pain are essential. In psychiatry, pain relief represents relaxation and a feeling of comfort and satisfaction, which suggests that cognitive and emotional motivations are important factors in the treatment of neuropathic pain. The comorbidity of chronic pain and psychiatric disorders, which is well recognized, suggests that the effective therapeutic relief for neuropathic pain induced by SCI can be achieved in conjunction with the management of the sensory and psychiatric aspects of patient.In this review, we address the feasibility of a combined acupuncture and pharmacotherapy treatment for the relief of neuropathic pain behavior following SCI.     

脊髓损伤后神经源性膀胱的个体化康复护理

目的 探讨脊髓损伤后神经源性膀胱的最佳护理方法。方法 60例脊髓损伤后排尿障碍患者随机分为2组，分别采用传统护理法和个体化护理法，比较两组患者自主排尿时问和泌尿系统并发症发生率的差别，从而找到适宜的护理方法。结果 个体化护理组患者自主排尿早，并发症少。结论 针对脊髓损伤后神经源性膀胱的不同特点，实施个体化护理措施，更有利于膀胱功能恢复。     

Effect of NMDA NR2B antagonist on neuropathic pain in two spinal cord injury models

N-Methyl-d-aspartate (NMDA) receptors are thought to play an important role in the processes of central sensitization and pathogenesis of neuropathic pain, particularly after spinal cord injury (SCI). NMDA antagonists effectively reduce neuropathic pain, but serious side effects prevent their use as therapeutic drugs. NMDA NR2B antagonists have been reported to effectively reduce inflammatory and neuropathic pain. In this study, we investigated the effects of NR2B antagonists on neuropathic pain and the expression of NR2B in the spinal cord in 2 SCI models. SCI was induced at T12 by a New York University impactor (contusion) or by sectioning of the lateral half of the spinal cord (hemisection). Ifenprodil (100, 200, 500, 1000nmol) and Ro25-6981 (20, 50, 100, 200nmol) were intrathecally injected and behavioral tests were conducted. Ifenprodil increased the paw withdrawal threshold in both models but also produced mild motor depression at higher doses. Ro25-6981 increased the mechanical nociceptive threshold in a dose-dependent manner without motor depression. NR2B expression was significantly increased on both sides at the spinal segments of L1-2 and L4-5 in the hemisection model but did not change in the contusion model. Increased expression of NR2B in the hemisection model was reduced by intrathecal ifenprodil. These results suggest that intrathecal NMDA NR2B antagonist increased the mechanical nociceptive threshold after SCI without motor depression. A selective subtype of NMDA receptor, such as NR2B, may be a more selective target for pain control because NMDA receptors play a crucial role in the development and maintenance of chronic pain.     

Metabolite concentrations in the anterior cingulate cortex predict high neuropathic pain impact after spinal cord injury

Persistent pain is a common reason for reduced quality of life after a spinal cord injury (SCI). Biomarkers of neuropathic pain may facilitate translational research and the understanding of underlying mechanisms. Research suggests that pain and affective distress are anatomically and functionally integrated in the anterior cingulate cortex and can modulate sensory and affective aspects of pain. We hypothesized that severe neuropathic pain with a significant psychosocial impact would be associated with metabolite concentrations (obtained by magnetic resonance spectroscopy) in the anterior cingulate cortex, indicating neuronal and/or glial dysfunction. Participants with SCI and severe, high-impact neuropathic pain (SCI-HPI; n = 16), SCI and moderate, low-impact neuropathic pain (SCI-LPI; n = 24), SCI without neuropathic pain (SCI-noNP; n = 14), and able-bodied, pain-free control subjects (A-B; n = 22) underwent a 3-T magnetic resonance imaging brain scan. Analyses revealed that the SCI-HPI group had significantly higher levels of myoinositol (Ins) (P < .000), creatine (P = .007), and choline (P = .014), and significantly lower levels of N-acetyl aspartate/Ins (P = .024) and glutamate-glutamine (Glx)/Ins (P = .003) ratios than the SCI-LPI group. The lower Glx/Ins ratio significantly discriminated between SCI-HPI and the A-B (P = .006) and SCI-noNP (P = .026) groups, displayed excellent test-retest reliability, and was significantly related to greater pain severity, interference, and affective distress. This suggests that the combination of lower glutamatergic metabolism and proliferation of glia and glial activation are underlying mechanisms contributing to the maintenance of severe neuropathic pain with significant psychosocial impact in chronic SCI. These findings indicate that the Glx/Ins ratio may be a useful biomarker for severe SCI-related neuropathic pain with significant psychosocial impact.