Spinal cord hyperexcitability and its role in pain and hyperalgesia

Sensitization of spinal cord nociceptive neurons is commonly interpreted as the cause for the hypersensitivity that characterizes chronic pain states in humans. However, in spite of much basic research in this area it has not been possible to demonstrate a direct link between the hyperexcitability of spinal cord neurons observed experimentally and the underlying mechanism of a chronic pain state. The word sensitization is also used in the literature with various and different meanings from the qualification of a cellular process of enhanced excitability at synaptic level to the characteristics of a chronic pain syndrome. In this article the various meanings of sensitization are described and the relevance of the hyperexcitability of spinal cord neurons to the generation of clinically relevant pain states is discussed. A proposal is made to restrict the use of the word sensitization to the cellular process of enhanced excitability observed experimentally after repetitive stimulation of nociceptive afferents. Caution is also recommended when associating neuronal sensitization in the spinal cord with the mechanisms of chronic pain conditions.     

丹参对脊髓损伤后伤区血流量及血液流变学指标的影响

目的 :比较应用丹参对兔脊髓损伤 (SCI)后伤区血流量及血液流变学指标的影响 ,探讨丹参对脊髓损伤的保护机制。方法 :5 8只成年日本大耳白兔 ,随机分成四组 ,A组 10只 ,作为正常组 ;B、C、D组各 16只 ,分别作对照组、地塞米松 (Dex)治疗组和丹参治疗组。比较脊髓损伤前后及应用Dex、丹参治疗后伤区血流量 (SCBF)及血液流变学指标的变化。结果 :脊髓损伤后 ,SCBF下降 ,血液粘度(ηb)、纤维蛋白原 (Fib)、细胞聚集指数 (RAI)增高。Dex对脊髓SCBF和血液流变学指标异常的改善不明显 ,而使用丹参治疗后 ,脊髓SCBF增高 ,血液流变学指标明显改善。结论 :丹参对脊髓损伤具有保护作用 ,且疗效较Dex明显 ,为临床治疗提供依据。     

脊髓血供及其监测研究

本文主要对脊髓的血供及目前的用于监测脊髓血供的方法和未来可能应用的新技术做一个综述,旨在协助临床脊柱外科医生能更好地对脊髓血供进行监测,预防脊髓缺血的发生,减少脊髓缺血所引起的损伤。     

脊髓损伤患者不当康复锻练致双足跟IV级压疮1例分析及护理

脊髓损伤合并截瘫的患者由于体位制动,长期卧床,大小便失禁,极易发生压疮,影响治疗和预后,不恰当的康复方法,更增加压疮的风险,现对1例脊髓损伤患者不当康复锻练致双足跟IV级压疮进行分析。护理人员应综合评估患者情况,循序渐进,早期规范康复介入并配置个体截瘫支具可明显提高日常生活能力及患者步行功能。     

脊髓损伤后神经源性膀胱患者护理中集束化康复护理的应用分析

目的 研究脊髓损伤后神经源性膀胱患者护理中集束化康复护理的应用。方法 选取于2016年2月~2017年5月入院68例脊髓损伤后神经源性膀胱患者作为研究对象,按照随机数字表法分为对照组和研究组,每组39例。对照组选用常规方式予以护理,研究组基于常规方式选用集束化康复护理模式;比较两组脊髓损伤后神经源性膀胱患者护理后满意度与护理前后膀胱容量、残余尿量。结果 研究组护理后满意度为97.44%,高于对照组79.49%,差异有统计学意义（P＜0.05）。研究组护理前后膀胱容量分别为（199.64±20.05）ml、（408.87±23.14）ml,护理前后残余尿量分别为（185.29±19.86）ml、（69.71±11.75）ml,对照组护理前后膀胱容量分别为（199.73±20.12）ml、（300.41±19.88）ml,护理前后残余尿量分别为（184.93±19.94）ml、（107.64±15.28）ml,两组患者护理后膀胱容量、残余尿量优于护理前,差异有统计学意义（P＜0.05）;研究组护理后膀胱容量、残余尿量优于对照组,差异有统计学意义（P＜0.05）。结论 脊髓损伤后神经源性膀胱患者护理中集束化康复护理的应用效果显著,可供临床参考。     

Spinal cord injury,immunodepression, and antigenic challenge

The inability to effectively control microbial infection is a leading cause of morbidity and mortality in individuals affected by spinal cord injury (SCI). Available evidence from clinical studies as well as animal models of SCI demonstrate that increased susceptibility to infection is derived from disruption of central nervous system (CNS) communication with the host immune system that ultimately leads to immunodepression. Understanding the molecular and cellular mechanisms governing muted cellular and humoral responses that occur post-injury resulting in impaired host defense following infection is critical for improving the overall quality of life of individuals with SCI. This review focuses on studies performed using preclinical animal models of SCI to evaluate how injury impacts T and B lymphocyte responses following either viral infection or antigenic challenge.     

Spinal cord injury impacts B cell production,homeostasis, and activation

Complex interactions govern the interplay of central nervous and immune systems, including the generation, homeostatic maintenance, and activation of B cells. Accordingly, spinal cord injury will likely impact all of these processes. Several laboratories have recently explored this possibility, and their observations in aggregate reveal both acute and chronic consequences that can vary based on the injury location. Acute effects include a transient cessation of bone marrow B lymphopoiesis, with a corresponding drop in the peripheral follicular and transitional B cell subsets, whereas the marginal zone subset is preserved. Despite recovery of B lymphopoiesis by 28 days post injury, follicular B cell numbers remain depressed; this may reflect reduced levels of the homeostatic cytokine BLyS. In general, the ability to mount T dependent antibody responses after injury are intact, as are pre-existing memory B cell pools and antibody levels. In contrast, T-independent responses are chronically compromised. Both glucocorticoid-dependent and -independent processes mediate these effects, but a detailed understanding of the mechanisms involved awaits further study. Nonetheless, these observations in toto strengthen the growing appreciation for bidirectional interactions between the CNS and immune system, highlighting the need for further basic and translational efforts.     

高颈段椎管内外肿瘤26例临床分析

目的：探讨高颈段椎管内外肿瘤误诊原因、手术入路选择及手术操作技巧。方法：26例高颈段椎管内外肿瘤均经CT或／和MRI检查确诊后行手术治疗，肿瘤全切除22例，次全切除4例。结果：痊愈18例，好转5例，无变化2例，恶化1例。结论：高颈段椎管内外肿瘤的确诊应首选MRI检查；显微外科手术是本病最根本的治疗方法，手术入路选择应视肿瘤位置，大小而定，熟练的显微神经外科技术，患者正常呼吸功能的维持及妥善的术后处理是治疗能否成功的关键因素。     

Morphology and Morphometry of Human Chronic Spinal Cord Injury Using Diffusion Tensor Imaging and Fuzzy Logic

Diffusion tensor imaging (DTI) was performed on regions rostral to the injury site in four human subjects with chronic spinal cord injury (SCI) and equivalent regions in four neurologically intact subjects. Apparent diffusion coefficients were measured and compared between subjects. A fuzzy logic tissue classification algorithm was used to segment gray and white matter regions for morphometric analysis, including comparisons of cross-sectional areas of gray and white matter along with frontal and sagittal diameters. Results indicated a general decrease in both longitudinal and transverse diffusivity in the upper cervical segments of subjects with chronic SCI. Further, a decrease in the cross-sectional area of the entire spinal cord was observed in subjects with SCI, consistent with severe atrophy of the spinal cord. These observations have implications in tracking the progression of SCI from the acute to the chronic stages. We conclude that DTI with fuzzy logic tissue classification has potential for monitoring morphological changes in the spinal cord in people with SCI.     

急性脊髓损伤后胶质酸性蛋白表达变化及意义

目的 观察急性脊髓损伤(SCI)后大鼠后肢功能恢复情况，以及损伤后胶质酸性蛋白(GFAP)表达的变化。方法 取雌性SD大鼠32只随机分为4组(n=8)：假手术组、伤后5d、9d、18d组．Allen法致伤脊髓．用大鼠综合行为评分法(CBS)对各级神经功能评分。用免疫荧光化学染色和图像分析的方法观察GFAP表达变化。结果 1．在行为观察中，发现大鼠脊髓损伤后有自行恢复倾向，损伤后18天后肢功能恢复67．5％。2．脊髓损伤后18d GFAP表达明显增强。结论 1、急性脊髓损伤后脊髓有自我修复的倾向。2、胶质细胞对脊髓损伤后的功能恢复起到重要作用。     

碱性成纤维细胞生长因子对脊髓缺血／再灌注损伤的保护作用

目的观察碱性成纤维细胞生长因子（basic fibroblast growth factor,bFGF）对脊髓缺血／再灌注损伤的保护作用。方法建立大鼠脊髓缺血／再灌注损伤动物模型。实验分对照组、缺血／再灌注组和bFGF组。测定血浆丙二醛、肌酸磷酸激酶、谷草转氨酶和乳酸脱氢酶含量。测定脊髓标本丙二醛、内皮素、细胞线粒体钙含量和组织湿／干重比值。结果缺血／再灌注组与对照组比较,血浆和脊髓的各项生化指标显著增高（P〈0．05）;使用bFGF后,血浆及脊髓各项测定指标较缺血／再灌注组相比明显降低（P〈0．05）。结论bFGF可减轻脊髓缺血／再灌注损伤,对脊髓有保护作用。     

Autonomic,sensory, and motor dysfunction following intrathecal administration of three substance P antagonists*

Summary Antagonists of the putative peptide neurotransmitter substance P have been found to produce pronounced cardiovascular effects when administered into the spinal subarachnoid space. These previous studies have not, however, provided any direct evidence that these effects result from interaction with substance P receptors. The present study was designed to characterize the modification of cardiovascular function resulting from administration of these compounds, and evaluate their effects on the integrity of spinal cord function. Intrathecal administration of two substance P antagonists produced a depressor response accompanied by a reduction of hindquarter vascular resistance. Following administration of a substance P antagonist, the integrated cardiovascular responses to electrical stimulation of the renal afferent nerves and ventrolateral medulla were markedly attenuated. Intrathecal administration to conscious rats of three substance P antagonists led to a variety of sensory and motor dysfunctions, including loss of spontaneous motor function, responsiveness to mechanical and thermal stimuli, and bladder function. No such effects were produced by administration of substance P, luteinizing hormone releasing hormone (LHRH), or LHRH antagonist. These effects from administration of a substance P antagonist were associated with a dose-dependent necrosis of spinal cord tissue. The necrosis may be secondary to ischemia since pretreatment with the vasodilator adenosine significantly delayed or blocked the sensory and motor dysfunctions. This conclusion was supported by the demonstration that cerebrovascular smooth muscle (pial vessels) was constricted by a SP antagonist. Taken together, these data suggest that substance P antagonists appear to non-specifically block transmission in the spinal cord, by mechanisms which may involve reduction of blood flow to the spinal cord.Supported by grants HL-14388, GM07069, and a gift from the Searle Family Trust Fund     

P物质参与调控骨髓间充质干细胞源性成骨细胞的矿化

目的观察不同浓度、不同时间P物质(substance P,SP)对骨髓间充质干细胞源性成骨细胞矿化的影响,并用SP非特异性的阻滞剂和NK1受体特异性的阻滞剂进行干预,从而推测其作用细胞的靶受体。方法 10只雄性6周龄SD大鼠制作脊髓损伤模型。从模型的胫骨、股骨提取骨髓间充质干细胞(mesenchymal stemcells,MSCs)进行成骨细胞的诱导培养,用第二代细胞进行实验。施加不同浓度的SP,对照组不加任何处理因素,在不同的时间点观察骨髓MSCs源性成骨细胞的矿化。并用SP、Spantide(SP的抑制剂)、L703606(NK1受体的抑制剂)进行配伍作用,观察骨髓MSCs源性成骨细胞的矿化。结果不同浓度的SP对细胞的矿化有不同程度的抑制作用,10~(-8)M浓度的抑制作用最强,矿化结节面积较对照组平均减少了38.3%(P0.01),随时间的延长抑制作用越强(3W:-34.9%,P0.01)。细胞矿化的抑制可以被Spantide和L703606所逆转,与SP组比较两组矿化分别升高了45.3%和50.5%。结论 SP通过NK1受体对成骨细胞的矿化产生影响。SP抑制了成骨细胞的矿化,使成熟的成骨细胞减少,从而引起脊髓损伤后骨质疏松的发生。     

Pain behavior and spinal cell activation due to carrageenan-induced inflammation in two inbred rat strains with differential hypothalamic–pituitary–adrenal axis reactivity

Lewis (LEW) and Fischer (FIS) inbred rats were used to study the relationship of hypothalamic–pituitary–adrenal (HPA) axis reactivity with inflammation-related pain behavior. LEW rats are susceptible to the development of autoimmune and chronic inflammatory disorders, whereas FIS rats are resistant. Since contradictory data have previously been collected under conditions of acute inflammation, we investigated the onset and maintenance of thermal and mechanical hyperalgesia and spinal activation of neurons and glia cells in a model of ongoing inflammation in both strains. Hind paw volumes and mechanical and thermal pain thresholds were measured prior to and during one week after intraplantar injection of carrageenan. The activation of nociceptive neurons (FosB), astroglia (GFAP) and microglia (OX-42) in the spinal cord of segments L5/L6 was assessed using immunohistochemistry. Inflammation increased paw volume, pain sensitivity and cell activation in both strains. FIS rats were more sensitive to sensory stimulation and developed a more severe edema on day 1, but recovered faster up to day 7 than LEW rats. At that time a higher amount of activated nociceptive neurons and corticosterone was seen in FIS rats, but microglial activation was more pronounced in LEW rats. Our results suggest a biphasic role of the HPA axis in pain behavior and spinal cell activation associated with ongoing inflammation. In the acute stage, the stronger reaction in FIS rats might be explained by an activating effect of corticosteroids on neutrophil function. Under ongoing inflammatory conditions the immunosuppressive actions of corticosteroids may dominate and lead to a quicker recovery of paw volume and pain sensitivity in FIS rats.     

康复护理对无骨折脱位型颈脊髓损伤患者 椎管扩大成形术后的影响

目的 探讨康复护理对无骨折脱位型颈脊髓损伤患者椎管扩大成形术后的影响。方法 选取2018年1月~6月于我院行手术的无骨折脱位型颈脊髓损伤患者60例作为研究对象,按照随机数表法分为研究组和对照组,每组30例。研究组采用康复护理进行术后护理,对照组采用常规护理。比较两组患者术后神经功能改善情况和并发症发生率。结果 研究组颈部神经功能改善的优良率为80.00%,高于对照组的60.00%,差异有统计学意义（P＜0.05）;研究组术后并发症发生率为10.00%,低于对照组的23.33%,差异有统计学意义（P＜0.05）。结论 康复护理能够促进无骨折脱位型颈脊髓损伤患者椎管扩大成形术后的神经功能恢复,减少术后并发症发病几率。     

Serotonin-positive fibers within the spinal motor nucleus of the newborn rat, with special reference to co-localization of substance P

Developmental changes of serotonin-positive fibers with special reference to co-localization with substance P was examined immunohistochemically in the ventral horn of rat lumbar spinal cord. Only about 20% of serotonin-positive fibers co-labelled with substance P on postnatal day (P) 0. The ratio of co-localization gradually increased, and reached the adult value by P28 (60–70%). Enkephalin-positive fibers were not co-localized with serotonin at any age examined. Although the densities of serotonin, substance P and enkephalin per unit area of the ventral horn gradually increased with development up to P28, the density of serotonin in the adult was decreased compared to P28 animals.     

小鼠海马结构与脊髓损伤后抑郁症高发病率的关系研究

目的:探究脊髓损伤引发的抑郁高风险率是否与海马生理结构的改变有关。方法:制作小鼠脊髓损伤模型,分别在损伤后不同时期采用Basso Mouse Scale(BMS)评分对小鼠术后运动功能进行评估;并通过糖水偏好实验和悬尾实验评估小鼠的抑郁情况;HE染色观察海马组织内部细胞的变化;电镜观察海马亚细胞结构突触的结构变化;RT-qPCR检测突触蛋白标志物突触小泡蛋白(SYP)和突触后致密蛋白95(PSD-95)在mRNA水平上的变化。结果:行为学实验显示模型组小鼠有显著的抑郁行为,且在第7天抑郁程度最显著(P<0.01);HE染色显示,与对照组相比,模型组海马细胞排列紊乱,数量减少,形态欠规则;电镜结果显示,与对照组相比,模型组海马超微结构突触数量减少,突触活动区长度变短,突触后致密物厚度变薄,突触间隙宽度增加,突触界面曲率减小(P<0.05);RT-qPCR结果显示模型组SYP和PSD-95 mRNA表达水平较对照组降低(P<0.05)。结论:海马生理结构的改变是脊髓损伤后抑郁症高风险的原因之一。     

MEK5/ERK5在大鼠脊髓损伤修复过程中表达水平动态变化及临床意义

目的 以大鼠为模型观察脊髓损伤修复过程中MEK5/ERK5(mitogen extracellular signal-regulated kinase 5/extracellular signal kinase 5)表达水平变化及临床指导意义.方法 将成年健康雄性大鼠随机分为实验组和假手术组,应用western-blotting蛋白质印迹技术和Real-Time PCR实时荧光定量检测技术分别检测脊髓损伤后1天,3天,7天,14天后MEK5、ERK5两种蛋白及其mRNA表达水平动态变化情况,通过考察P-ERK(phosphorylated extracellular signal kinase 5)表达水平考察ERK5激活情况.结果 RT-PCR显示实验组组MEK5 mRNA和ERK5 mRNA表达水平均随时间呈逐渐增加的动态变化规律,且与假手术组相比表达水平明显增加;Western blotting显示实验组MEK5表达水平随时间先增加后回落,ERK5表达水平随时间逐渐增加,P-ERK表达水平随时间增加.结论 ERK5表达水平与脊髓损伤修复过程呈正相关,ERK5的促组织细胞分裂增殖的功能可能有助于脊髓损伤加速修复.     

脊髓损伤并四肢粉碎性骨折的治疗体会(附18例报告)

目的：探讨脊髓损伤并四肢粉碎性骨折病人四肢骨折的处理。方法：对18例脊髓损伤并四肢骨折病例，急诊行椎管减压、复位及椎弓根钉板系统内固定术，并予激素冲击疗法，四肢骨折同时行切开复位加压钢板螺钉内固定加植骨术，配合使用促进骨愈合、扩张血管、及保护胃粘膜等药物及高压氧治疗。结果：所有病例均获得随访，平均随访时间2a4个月。18例四肢骨折均获临床骨性愈合，愈合时间6～12周，平均7．6周。无骨不连发生。其中11例已取出内固定，无再骨折。结论：脊髓损伤合并四肢粉碎性骨折的病例，早期在处理脊髓损伤的同时，四肢骨折采用坚强内固定加植骨术，可以预防四肢骨折术后骨不连的发生。便于护理，利于脊髓及肢体功能的康复。