脊髓背根神经节河豚毒素不敏感钠通道"再分布"可能导致急性切口痛敏现象

目的 研究急性切口痛模型中脊髓背根神经节(DRG)河豚毒素不敏感型钠通道(TTX-R)信使核糖核酸(mRNA)表达、通道分布改变,探讨急性切口痛这种复合炎性痛和神经源性疼痛的分子基础,并探讨钠离子通道在其中的可能作用.方法 30只SD大鼠随机均分为两组,实验组(A组):大鼠右足底行1 cm长手术切口建立急性痛模型;对照组(B组):行假手术处理.原位杂交、实时(RT)-PCR监测术前、术后24、48、96 h右侧L4～L6DRG上Nav1.8和Nav1.9 TTX-R钠通道mRNA表达水平、通道分布情况的变化.结果 原位杂交和RT-PCR表明两组Nav1.8和Nav1.9的mRNA水平差异无统计学意义,但A组在术后各时点不同直径DRG细胞上存在"再分布"现象.结论 DRG细胞TTX-R钠通道"再分布"现象可能在急性切口痛模型痛敏状态中起到一定作用.     

Dermatomal laser-evoked potentials: a diagnostic approach to the dorsal root. Norm data in healthy volunteers and changes in patients with radiculopathy

We conducted a cross-sectional study of 40 radiculopathy patients in comparison with norm data from healthy subjects using a new electrophysiological method. Early manifestations of dorsal root impairment escape objective diagnosis by conventional somatosensory-evoked potentials due to the overlapping innervation of the affected dermatome by thickly myelinated mechanoreceptive afferents projecting to adjacent intact roots. Evidence suggested less intersegmental overlap for thermonociceptive afferents rendering laser-evoked potentials (LEP) sensitive to monosegmental dorsal root damage. Therefore we used this new method to study acute manifestations of monosegmental dorsal root pathology. Dorsal root function was tested in 12 healthy subjects and 40 sciatica patients by intraindividual interside comparison. Mechanosensibility and thermosensibility were clinically investigated. LEP were induced by moderately painful laser stimuli. The LEP were evaluated by amplitude and latency of the averaged electroencephalogram. Normal interside differences of LEP for amplitude were ±22% (lower limb) and ±35% (upper limb) and ±15 to ±16% for latency. Twenty-six patients (65%) showed significant LEP changes, mainly amplitude decreases. Six of these patients exhibited latency prolongations. Clinical testing yielded more frequent pathological results for pain compared to mechanosensibility. The study confirmed our preliminary evidence of LEP sensitivity to objectively document dorsal root impairment in patients suffering from acute monosegmental radiculopathy. This result opens the perspective of electrophysiologically differentiating the presence or absence of dorsal root pathology in patients with similar clinical symptoms but possibly different prognoses, which require different therapies.     

Magnetic resonance imaging findings of the lumbar root pathway in patients over 50 years old

Summary In patients with degenerative disease of the lumbar spine, stenosis not only in the entrance zone but also in the mid- and exit zones of the nerve root pathway can occur. With the development of magnetic resonance imaging (MRI), it has become easier to assess stenosis of the root pathway, especially in the mid- and exit zones. T1-weighted sagittal images in the lateral facet plane show the state of the exit zone. I studied the incidence of severe exit-zone stenosis of L3-5 roots in 45 patients aged over 50 years 15 in their fifties, 15 in their sixties, and 15 in their seventies) by MRI and assessed the results on the basis of age, intervertebral disc degeneration, and disc height. I also studied the relationship between clinical symptoms and severe stenosis in both entrance and exit zones of the L4 and L5 roots. The incidence of severe exit-zone stenosis at the L3 root was 20% at all ages. On the other hand, L4 and L5 nerve root stenosis increased with age and severe stenosis affected 70% of L4 roots and 80% of L5 roots in patients in their seventics. The incidence of deformation or disappearance of the dorsal root ganglion (DRG) was 10% or less at L3 and L5 roots, while it was 10% at L4 root. The incidence of severe stenosis both in entrance and exit zones in a single root was 20% at L4 root in all age groups, while it was 19% of patients in their fifties and increased to 29% of patients in their sixties and then 46% of patients in their seveties at L5 root. This study showed the high frequency of root pathway stenosis at L4 and L5 in the degenerative lumbar spine. However, not all patients with exit stenosis suffered from radicular symptoms. Stenosis in the mid- and exit zones of the root pathway has been an important factor in failed back surgery. It seems to be important to determine whether entrance, mid- and exit zone stenosis exist or not in order to clarify the pathological conditions of patients, especially in disorders affecting L4 and L5 nerve roots. T1-weighted MRI images can provide useful information concerning lesions in the mid- and exit zones in the degenerative lumbar spine.     

脊神经节血-神经屏障的超微结构特点及损伤的影响

目的　探讨脊神经节（ Ｄ Ｒ Ｇ） 血神经屏障的超微结构特点, 损伤的影响及临床意义。　方法　健康家兔４２ 只, 实验 分为手 术对照、机械 性压迫 组和炎 性损伤 组, 并 采用伊 文氏蓝 白蛋白（ Ｅ Ｂ Ａ） 和辣根过氧化酶（ Ｈ Ｒ Ｐ） 示踪剂观测。　结果　正常 Ｄ Ｒ Ｇ 不但缺乏有效的血神经屏障, 而且也缺乏有效的神经束膜弥散屏障。　结论　 Ｄ Ｒ Ｇ 不但易受血液循环环境改变的影响, 而且也易受局部环境变化的影响,这是 Ｄ Ｒ Ｇ 易受损伤的形态结构特征之一,同时也为局部用药提供可能     

Laser-evoked potentials: prognostic relevance of pain pathway defects in patients with acute radiculopathy

The radicular pain syndrome is a major problem in public health care that can lead to chronic back and leg pain in 30%. Ischalgia and back pain are the most prominent signs of dorsal root affection. Until now, no clinical or neurophysiological test procedure exists that evaluates the function of the dorsal root and predicts the prognosis of patients suffering from RPS. We have recently demonstrated that laser-evoked potentials (LEP) are able to demonstrate dorsal root damage. With this study, we investigated 54 patients with acute radicular symptoms and compared LEP parameters (side to side difference of latency and amplitude, transformed to a z-score) with their state of health after 3 months to calculate their predictive value for outcome prognosis. Most significantly, the latency difference between the LEP of the affected dermatome relative to the contralateral healthy dermatome was able to predict the prognosis. Latency z score above two demonstrates a 91% specificity (33% sensitivity) for a poor outcome at 3 months. A significant relation between amplitude changes and the main outcome measure could not be shown. Only extreme changes (z score >10) in amplitude show a high specificity for the persistence of ischialgia in particular (specificity 0.94; sensitivity 0.35). All other parameters, such as clinical scores or other LEP parameters, were not able to predict the outcome of patients. We propose that clinical testing using LEP with latency analysis is a useful tool for estimating the course of disease, so that patients with poor predictive parameters can be treated more invasively at early disease stages to avoid persistence of radiculopathy.     

脊神经节损伤介导的脊髓背角EAAs和IAAs变化的实验研究

目的：研究脊神经节（ＤＲＧ）炎性损伤时,脊髓背角兴奋性氨基酸（ＥＡＡｓ）、抑制性氨基酸（ＩＡＡｓ）含量和脊髓背角谷氨酸（Ｇｌｕ）、天门冬氨酸（Ａｓｐ）免疫组织化学的变化,及其与实验动物神经行为异常变化之间的关系。方法：健康家兔５４只,随机分为手术对照组（ｎ＝２４）;炎症损伤组（ｎ＝２４）和正常对照组（ｎ＝６）。采用组织氨基酸的含量分析仪测定脊髓背角Ｇｌｕ、Ａｓｐ、γ氨基丁酸（ＧＡＢＡ）、牛磺酸（Ｔａｕ）、苏氨酸（Ｔｈｒ）和色氨酸（Ｓｅｒ）含量,采用免疫组化法观察脊髓背角Ｇｌｕ和Ａｓｐ分布特点及变化。结果：ＤＲＧ炎症损伤介导脊髓背角ＥＡＡｓ和ＩＡＡｓ释放增加。结论：ＥＡＡｓ在痛觉过敏的形成和维持中具有重要作用,而ＩＡＡｓ的增加则与机体抗伤害性保护反应相关。ＤＲＧ炎症损伤初期,脊髓背角ＥＡＡｓ／ＩＡＡｓ动态平衡的破坏是伤害性神经细胞兴奋性损伤和伤侧肢体痛觉过敏的主要原因。     

Loss of Type A neuronal cells in the dorsal root ganglion after a non-severe full-thickness burn injury in a rodent model

Burn scars can be associated with significant loss of cutaneous sensation, paresthesia and chronic pain. Long-term systemic changes in cutaneous innervation may contribute to these symptoms and dorsal root ganglia have been implicated in the development of chronic neuropathic pain. Therefore we hypothesized that changes in cutaneous innervation after burn injury may be mediated at the level of the dorsal root ganglia. Burn group rats (n = 20) were subjected to a unilateral burn injury while 12 control rats underwent sham procedure. The DRGs dermatomally related to the site of burn (Thoracic 13, lumbar 1 and lumbar 2), ipsilateral and contralateral to the injury, were compared for Type A, Type B and total cell number with sham control DRGs, at 4 and 6 weeks after injury. There was a significant decrease in Type A cell count (cell bodies of nerve fibres mediating touch-pressure-vibration sensation) in the 4 week time-point group (p = 0.0124) ipsilateral to the burn injury. Total DRG cell count and Type B DRG cell count (cell bodies of fibres mediating pain and itch) on the ipsilateral side was not significantly altered. On the side contralateral to the burn injury, there was no statistically significant change in the total cell count, Type A cell count or Type B cell count. This data showed a decrease in Type A cell number in DRGs after a burn injury, suggesting cell death may mediate some changes observed in cutaneous innervation after a burn. Type B cells constituted a greater proportion of the viable cell population in the ipsilateral DRG after a burn injury. This change may be important in the induction of signalling related to pain and itch and has important implications for the restoration of normal cutaneous innervation after burn injury. Investigating whether neuro-protective or neuro-restorative approaches can ameliorate damage to the DRG will be important to improve sensory outcomes for burn patients.     

磷脂酶A2硬膜外腔注射对大鼠腰髓及背根节中CGRP含量的影响

目的探讨腰椎间盘突出症相关腰腿痛发病的可能机制.方法在大鼠的硬膜外腔注射磷脂酶A2,免疫组化的方法测定大鼠背根节和脊髓后角中CGRP的变化.结果硬膜外腔注射磷脂酶A2后,L4-6背根节中CGRP阳性神经元的数目和面积明显增加,脊髓背角浅层中CGRP阳性神经纤维终末的面积也明显增加.证实与对照组相比较有显著性差别(P＜0.05).结论磷脂酶A2是一种疼痛伤害性刺激,它可能在腰椎间盘突出相关腰腿痛的发病中起到重要的作用.     

大鼠椎骨错缝模型下丘脑及背根神经节P物质含量的实验研究

目的:检测腰椎椎骨错缝对大鼠下丘脑及背根神经节中P物质含量的影响。方法:选取120只体质量为350~450 g的SPF级雄性SD大鼠随机分为旋转固定组(RF组)、单纯固定组(SF组)和假手术组(Sham组)。RF组和SF组大鼠腰椎L4-L6节段植入的椎体外部连接固定装置,RF组大鼠使L5棘突向右侧旋转,造成L5棘突与L4和L6棘突的不共线;SF组大鼠单纯植入椎体外部连接固定装置不进行旋转。Sham组大鼠不植入椎体外部连接固定装置,只切开后缝合。分别于手术后1、4、8和12周结束时,检测各组大鼠下丘脑及背根神经节中P物质含量。结果:手术1、4、8周后,RF组和SF组大鼠下丘脑中P物质含量均低于Sham组大鼠(P<0.05);手术1、4、8、12周后,RF组和SF组大鼠背根神经节中P物质含量均高于Sham组大鼠(P<0.05);固定12周后,RF组和SF组大鼠下丘脑中P物质与Sham组比较差异无统计学意义(P>0.05)。结论:椎骨错缝可抑制下丘脑中P物质的镇痛作用,促进背根神经节中P物质的合成和传递,从而引起或加剧疼痛。     

环化酶激活剂对大鼠感觉神经元保护作用的实验研究

目的探讨环化酶激活剂（前列腺素E1、腺苷及Zn^2＋离子）对周围神经损伤后感觉神经元的保护作用.方法在大鼠坐骨神经夹毁模型术后21 d,取背根节用图像分析法观测前列腺素E1（PGE1）、腺苷（Ade）和高Zn^2＋饲料（Zn^2＋）对背根节细胞数、核偏心率及核等圆径的影响,并与人胎盘神经生长因子（hNGF）的作用相比较.结果NGF及环化酶激活剂组与夹毁对照组相比都能增进背根节细胞的存活和减轻核偏移（P＜0.05）;NGF组和高Zn^2＋饲料组在背根节细胞存活数、核偏心率及核等圆径方面与假手术组无差别（P＞0.05）.结论PEG1、Ade及Zn^2＋离子等环化酶激活剂对DRG神经元均有保护作用,其中Zn^2＋离子的保护效应与NGF无差别.     

Etanercept attenuates pain-related behavior following compression of the dorsal root ganglion in the rat

Purpose  

TNFα is an inflammatory mediator related to neuropathic pain including sciatica. Much basic research suggests that anti-TNFα therapy may be useful for the treatment of sciatica. The purpose of this study was to clarify the effects of etanercept in a dorsal root ganglion (DRG) compression model.     

The microstructure of peripheral nerves

An understanding of the normal peripheral nerve and its associated structures illuminates the events following a peripheral nerve injury. There are two overlapping stages: Wallerian degeneration followed by regeneration (Figure 10). Ideally, treatment interventions should be initiated early and take into account both of these phenomena. Although the physician cannot control the “biological battlefield” raging inside a damaged nerve, realistic goals according to Hall include: (1) therapy to keep more neurons alive; (2) encourage axons to cross longer interstump gaps; (3) maximize the accuracy of target reinnervation; and (4) manage the neuropathic pain.⁷     

加巴喷丁对糖尿病神经病理痛大鼠背根神经节Toll样受体4表达的影响

目的 探讨加巴喷丁(gabapentin,GBP)对糖尿病神经病理性疼痛(diabetic neuropathic pain,DNP)大鼠背根神经节(dorsal root ganglia,DRG)Toll样受体4(toll-like receptor 4,TLR4)表达的影响. 方法 108只成年健康雄性SD大鼠,采用完全随机分组法分为4组:对照组(C组)、模型组(DNP组)、生理盐水(SC)+DNP组和GBP+DNP组(每组27只).观察链脲佐菌素(streptozocin,STZ)注射前1d及注射后3、7、10、14、21、28 d测定缩足反射机械刺激阈值(paw withdrawal mechanical threshold,PWMT)和缩足反射热辐射潜伏期(paw withdrawal thermal latency,PWTL),SC+DNP组和GBP+DNP组于STZ注射15d起分别腹腔注射生理盐水或GBP 50 mg/kg,1次/d,连续7d,并于21、28 d测定PWMT和PWTL.行为学测试完成后选择21 d大鼠用免疫组化和Western blot方法检测大鼠DRG中TLR4的表达. 结果 与C组比较,DNP组PWMT (3.9±0.9)g降低,PWTL[(6.1±0.8)s]缩短,DRG中TLR4蛋白的表达显著上调(P＜0.05);与DNP组比较,SC+DNP组大鼠在腹腔注射生理盐水后,PWMT、PWTL和TLR4蛋白的表达无明显改变(P＞0.05);与DNP组和SC+DNP组比较,GBP+DNP组PWMT(8.3±0.8)g升高,PWTL[(9.9±1.2)s]延长,DRG中TLR4蛋白的表达下调(P＜0.05). 结论 GBP可通过抑制DRG中TLR4表达,从而减轻大鼠DNP.     

大鼠坐骨神经去感觉模型及其应用解剖学研究

目的 探讨大鼠坐骨神经感觉纤维在背根神经节的定位,建立大鼠坐骨神经去感觉模型.方法 采用True Blue坐骨神经逆行示踪法和大体解剖观察(17只大鼠,共34侧),了解大鼠坐骨神经感觉纤维起源于哪些背根神经节;在此基础上,选择性切除大鼠左侧L3～L6背根神经节(n=8),术后进行红外热痛觉测定和神经捏压试验,评价感觉去除情况.结果 神经逆行示踪显示坐骨神经感觉纤维的来源及比例如下:Ⅰ型,源自L4～L6,占58.8％;Ⅱ型,源于L4～L5,占8.8％;Ⅲ型,源于L3～L6,占23.5％;Ⅳ型,源自L3～L5,占8.9％.该组成和比例与大体解剖所见相似.切除大鼠左侧L3～L6背根神经节后,左足第五趾末节趾腹痛觉丧失,直接捏压术侧胫神经、腓总神经和腓肠神经时大鼠均无疼痛反应.结论 大鼠坐骨神经感觉纤维主要源于L4～L6背根神经节,但部分坐骨神经有L3参与,可通过切除一侧L3～L6背根神经节来建立大鼠坐骨神经去感觉传人模型.     

Pathology of lumbar nerve root compression. Part 2: morphological and immunohistochemical changes of dorsal root ganglion.

STUDY DESIGN: This study is to investigate the changes of dorsal root ganglion (DRG) induced by mechanical compression using in vivo model. OBJECTIVES: The effect of axonal flow disturbance induced by nerve root compression was determined in DRG. SUMMARY OF BACKGROUND DATA: The dorsal root ganglion should not be overlooked when considering the mechanism of low back pain and sciatica, so it is important to understand the morphologic and functional changes that occur in primary sensory neurons of the dorsal root ganglion as a result of nerve root compression. However, few studies have looked at changes of neurons within the dorsal root ganglion caused by disturbance of axonal flow and the axon reaction as a result of mechanical compression of the dorsal root through which the central branches of the primary sensory nerves pass. METHODS: In mongrel dogs, the seventh lumbar nerve root was compressed for 24 h, one week, or three weeks using a clip with a pressure of 7.5 gf. Morphologic changes of the primary sensory neurons in the dorsal root ganglion secondary to the axon reaction were examined by light and electron microscopy. Changes of immunostaining for substance P (SP), calcitonin gene-related peptide (CGRP), and somatostatin (SOM) in the primary sensory neurons affected by central chromatolysis after nerve root compression were also examined. RESULTS: Light microscopy showed central chromatolysis of neurons in the dorsal root ganglion from one week after the start of compression. Electron microscopy of the affected neurons revealed movement of the nucleus to the cell periphery and the loss of rough endo-plasmic reticulum and mitochondria from the central region. Immunohistochemical studies showed a marked decrease of SP, CGRP, and SOM staining in small ganglion cells with central chromatolysis when compared with cells from control ganglia. CONCLUSION: It is important to be aware that in patients with nerve root compression due to lumbar disc herniation or lumbar canal stenosis, dysfunction is not confined to degeneration at the site of compression, but also extends to the primary sensory neurons within the dorsal root ganglion as a result of the axon reaction. Patients with sensory disturbance should therefore be fully informed of the fact that these symptoms will not resolve immediately after surgery.     

Dorsal arthrodesis in prepubertal New Zealand white rabbits followed to skeletal maturity: Effect on thoracic dimensions, spine growth and neural elements

Background:

Several studies have shown that severe spinal deformity and early arthrodesis can adversely affect the development of the spine and thorax by changing their shape and reducing their normal function. This article analyzes the consequences of posterior fusion on the growth of spine, thorax and neural elements in New Zealand white rabbits and compares with similar human data.

Materials and Methods:

The first section of the article analyzes the consequences of T1-T6 dorsal arthrodesis on the growth of the spine, sternum, thorax volume and neural elements in 12 prepubertal female New Zealand white rabbits, through a study of CT scans and histology specimens. The second part, evaluates thoracic dimensions in 21 children with spinal arthrodesis for treatment of deformity performed prior to nine years of age.

Results:

Dorsal arthrodesis in prepubertal rabbits changes thoracic growth patterns. In operated rabbits thoracic depth grows more slowly than thoracic width. The sternum as well as length of thoracic vertebral bodies in the spinal segment T1-T6 show reduced growth. Children undergoing spinal arthrodesis before nine years of age were noted to have shortened height, short trunk and disproportionate body habitus at skeletal maturity. Observed spine height and chest dimension values were reduced compared to the expected norms. The ratio between chest width and chest depth was below normal values.

Conclusions:

The first part of the study shows that thoracic dorsal arthrodesis in prepubertal New Zealand white rabbit influences thoracic, spine growth and affects the shape of pseudo unipolar neurons of the dorsal root ganglia. The second part demonstrates that children treated before nine years of age have significantly reduced spine height and thoracic dimensions. The thorax becomes elliptical as chest depth grows less than chest width. Both experimental and clinical findings contribute to explain reduced chest growth and subsequent thoracic growth disturbance in patients treated with early arthrodesis.     

山羊脊神经后根逆向吻合生长的超微结构

目的：探索山羊脊神经后根逆向吻合生长后的超微结构。方法：选择山羊右侧L3～S1脊神经后根，每根取1／2切断，然后将L3与L5、L4与S1切断的脊神经后根的远端，用显微外科技术行端端吻合，4个月后取吻合段脊神经后根透射电镜观察。结果：吻合区既有有髓鞘神经纤维通过，也有无髓鞘神经纤维生长。结论：在蛛网膜下腔脊神经后根离断并逆向吻合后能和周围神经一样生长,山羊脊神经后根逆向吻合生长后，脊神经后根的微细结构发生变化，即在该脊神经后根纤维中，在外周段出现电兴奋传导方向相反的神经纤维，在中枢段出现来自拮抗肌的神经纤维，因此该脊神经后根的功能可能发生某些变化。     

鞘注神经生长因子促进大鼠胫骨骨折愈合的实验研究

目的 研究鞘注神经生长因子(NGF)对大鼠胫骨骨折愈合的影响,以及相应脊髓背根神经节(DRG)与胫骨骨痂中的降钙素基因相关肽、P物质的表达变化. 方法 成年雄性SD大鼠48只随机分为两组.实验组予NGF 1μg/d连续鞘注14 d,对照组予等量生理盐水.术后7、14、21、28 d分批处死动物,行骨痂X线评分、骨痂/骨干比值测量.免疫组织化学法测定相应节段DRG与胫骨骨痂中的CGRP、SP表达.结果 术后21 d,NGF组X线评分低于对照组,21 d、28 d骨痂/骨干比值低于对照组.HE染色显示各时期NGF组软骨内成骨过程增强,骨痂成熟度高于对照组,骨痂改建过程提前且更为完全.CGRP、SP在DRG及胫骨骨痂中表达的平均光密度(OD)值高于同期对照组,差异有统计学意义(P＜0.05).相关性分析显示DRG神经肽表达OD值与骨痂OD值明显正相关. 结论 鞘注神经生长因子可促进DRG与骨折骨痂中的神经肽表达,促进成骨细胞增殖与软骨内骨化,减小骨痂体积并加速骨折的愈合及塑形改建过程.推测神经生长因子与DRG神经肽参与了中枢神经调控外周成骨活动的过程.     

残根残冠的保存治疗与修复的临床效果分析

目的探讨残根残冠经根管治疗与冠修复后的临床治疗效果。方法选择2008～2010年在门诊收治的274颗残根残冠为研究对象,经根管治疗后行桩核冠修复,随访观察6个月-3年,分析其临床疗效。结果经6个月～3年随访,274颗患牙中244颗修复成功（89．1％）,30颗牙失败（10．9％）,其中16颗牙根出现不同程度的松动,8颗出现龈瘘,4颗因牙周炎拔牙,2颗核桩因继发龋脱落。结论在严格选择适应证的前提下,残根、残冠经完善根管治疗与冠修复后可达到满意的临床治疗效果。