髓核对大鼠腰神经根非压迫性损伤的组织形态学研究

目的　观察硬膜外移植自体髓核后 ,大鼠神经根组织形态学的变化。方法　 2 8只Sprague Dawley(SD)雄性大鼠随机分成对照组和实验组 ,分别将自体肌肉混悬液和尾椎髓核混悬液注射到腰椎硬膜外腔 ,对神经根组织进行形态学观察。结果　在无机械压迫情况下 ,大鼠硬膜外移植自体髓核能使马尾神经根组织形态产生明显改变。结论　髓核所致的炎性反应是引起神经根损伤和坐骨神经痛的重要原因之一     

髓核对大鼠脊神经节非压迫性损伤的组织形态学研究

目的 观察硬膜外移植自体髓核后，大鼠脊神经节组织形态学的变化。方法 20只Sprague—Dawley(SD)雄性大鼠随机分成对照组和实验组，分别将自体肌肉混悬液和尾椎髓核混悬液注射到腰椎硬膜外腔，对脊神经节组织形态学进行观察。结果 在无机械压迫情况下，大鼠硬膜外移植自体髓核能使脊神经节组织形态产生明显改变。结论 髓核所致的炎性反应是引起脊神经节损伤和坐骨神经痛的重要原因之一。     

大鼠非压迫性髓核突出模型的建立

目的:设计一种新的非压迫性腰椎间盘髓核突出动物模型。方法:16只SD雄性大鼠随机分对照组和实验组,分别将生理盐水和大鼠自身尾椎髓核混悬液注射到腰椎硬膜外腔,对其马尾神经传导速度和神经根组织形态学进行观察。结果:无明显机械压迫情况下,大鼠硬膜外移植自体髓核能使马尾神经根传导速度和组织形态产生明显改变。结论:本动物模型简单、可靠、费用低廉,为进一步研究腰椎间盘突出症提供了一种动物模型。     

大鼠非压迫性髓核突出模型的建立

目的:设计一种新的非压迫性腰椎间盘髓核突出动物模型.方法:16只SD雄性大鼠随机分对照组和实验组,分别将生理盐水和大鼠自身尾椎髓核混悬液注射到腰椎硬膜外腔,对其马尾神经传导速度和神经根组织形态学进行观察.结果:无明显机械压迫情况下,大鼠硬膜外移植自体髓核能使马尾神经根传导速度和组织形态产生明显改变.结论:本动物模型简单、可靠、费用低廉,为进一步研究腰椎间盘突出症提供了一种动物模型.     

大鼠非压迫性髓核突出模型的建立

目的：设计一种新的非压迫性腰椎间盘髓核突出动物模型。方法：16只SD雄性大鼠随机分对照组和实验组，分别将生理盐水和大鼠自身尾椎髓核混悬液注射到腰椎硬膜外腔，对其马尾神经传导速度和神经根组织形态学进行观察。结果：无明显机械压迫情况下，大鼠硬膜外移植自体髓核能使马尾神经根传导速度和组织形态产生明显改变。结论：本动物模型简单、可靠、费用低廉，为进一步研究腰椎间盘突出症提供了一种动物模型。     

柚皮苷硬膜外腔注射对髓核致坐骨神经痛大鼠的疼痛行为影响

目的研究柚皮苷硬膜外腔注射对致坐骨神经痛大鼠的疼痛行为学的影响。方法选择雄性SD大鼠28只,制作髓核致坐骨神经痛大鼠模型。随机分为4组,每组7只大鼠。术后第3天开始注药治疗,柚皮苷组每日硬膜外腔注入柚皮苷注射液50μl,地塞米松组每日硬膜外腔注入地塞米松注射液50μl,生理盐水组每日硬膜外腔注入生理盐水50μl,未注药组硬膜外腔无药物注入处理。检测大鼠术前,术后及给药后1、3、7、14d的疼痛行为指标（50％机械性刺激缩足阈值和热刺激缩足反应潜伏期）。结果4组大鼠在术后均对机械刺激产生明显的痛觉过敏,与术前比较差异有显著性（P〈0.05）;柚皮苷组与地塞米松组在提高疼痛行为学指标的作用方面差异无显著性（P〉0.05）。结论硬膜外腔注射柚皮苷可有效改善髓核致坐骨神经痛大鼠的疼痛反应。     

硬膜外移植自体髓核对大鼠神经根功能和组织学的影响

目的:探讨无机械压迫时,腰椎间盘髓核突出引起腰腿痛的发病机制.方法:用硬膜外穿刺的方法给大鼠注射生理盐水及自体髓核混悬液,并对机械刺激缩爪阈值、马尾神经传导速度,神经根组织形态、疼痛行为进行了测定和观察.结果:大鼠硬膜外移植自体髓核能产生明显的痛觉过敏反应,马尾神经传导速度和神经根组织形态产生明显改变.结论:髓核所致的炎症反应是引起坐骨神经痛的重要原因之一.     

硬膜外移植自体髓核对大鼠神经根功能和组织学的影响

目的：探讨无机械压迫时，腰椎间盘髓核突出引起腰腿痛的发病机制。方法：用硬膜外穿刺的方法给大鼠注射生理盐水及自体髓核混悬液，并对机械刺激缩爪阈值、马尾神经传导速度，神经根组织形态、疼痛行为进行了测定和观察。结果：大鼠硬膜外移植自体髓核能产生明显的痛觉过敏反应，马尾神经传导速度和神经根组织形态产生明显改变。结论：髓核所致的炎症反应是引起坐骨神经痛的重要原因之一。     

白细胞介素-1α在髓核源性神经根性疼痛中的作用

目的:探讨白细胞介素-1琢(IL-1琢)是否参与髓核突出所致的坐骨神经疼痛的产生。方法:将大鼠自体尾椎的髓核无压迫下放置在L4和L5神经根表面,在术后不同时间测量大鼠后足对机械刺激敏感性的变化,同时用免疫组化方法对移植髓核中的IL-1琢进行检测。结果:在无明显机械压迫的情况下,大鼠腰神经根上放置自体髓核后,术侧后足可产生明显机械刺激痛觉过敏;实验组大鼠移植髓核组织中IL-1琢免疫组织化学染色阳性。结论:髓核组织的生物学作用是引起腰腿痛的重要因素,炎性介质IL-1琢可能参与疼痛的发生。     

单侧坐骨神经干髓核移植对大鼠双足痛阈的影响及其可能机制的探讨

目的观测髓核组织对单侧坐骨神经干的损伤作用,探讨这种损伤作用与大鼠双足痛阈之间的关系。方法24只雄性SD大鼠(体重260~280g)随机分为四组:、假手术组、脂肪组、肌肉组、髓核组,每组n=6。另外3只雄性SD大鼠用来提供异体脂肪、肌肉和髓核,移植到各组一侧坐骨神经干,用神经行为学的方法观测大鼠双足痛阈变化,并于术后第10d、20d取植入侧坐骨神经用病理切片组织化学染色方法光镜观察坐骨神经干组织学变化。结果术后3、5、7、10、15、20、25、30、35d对照组双后肢均未出现痛觉过敏,而髓核组双侧后肢均出现明显的痛觉过敏,并且以术后7~10d最明显;组织学光镜观察发现髓核组植入侧坐骨神经干出现水肿、大量淋巴细胞浸润,部分髓鞘呈空泡样变等损伤表现,术后10d表现明显。结论髓核组织对坐骨神经干有炎性损伤作用,此损伤作用与痛觉过敏可能存在联系。     

实验性髓核突出诱致神经根性疼痛机理的探讨

目的 探索单纯自体髓核组织放置于神经根邻近,并与神经根接触后对大鼠后爪机械刺激痛觉敏感性的影响。方法 取大鼠自体尾椎髓核组织无压迫下置于腰4和腰5神经根旁并与神经根相接触,术后不同的时间点观察大鼠双侧后爪机械刺激敏感性的变化;同时采用HE染色方法观察髓核组织和神经根的变化。结果 无明显机械压迫情况下,自体髓核组织与神经根接触后可诱导大鼠术侧后爪出现明显的机械性痛觉敏感性的升高;HE染色显示髓核组织发生了明显的炎性改变,邻近神经根出现空泡变性。结论 髓核组织自身介导的炎症反应可能参与机械性痛觉敏感性的发生。除机械因素外,突出髓核组织发生的炎症反应也可能是腰椎间盘突出所致坐骨神经痛的原因。     

Mechanical compression of the lumbar nerve root alters pain-related behaviors induced by the nucleus pulposus in the rat.

The purpose of this study was to refine a method of nerve-root injury in the rat to produce hyperalgesia, a pain-related behavior, and to determine if there were any relationships between the histological extent of nerve-root injury and the magnitude of hyperalgesia. Three methods were used to produce hyperalgesia: irritation of a nerve root by ectopic nucleus pulposus, silk loop alone, or both silk loop and ectopic nucleus pulposus. Autologous nucleus pulposus obtained from coccygeal intervertebral discs was relocated on the lumbar nerve roots after laminectomy. Two loops of 4-0 silk were placed around the exposed nerve roots. Hyperalgesia was measured preoperatively and postoperatively. The distribution of myelinated axons in the dorsal nerve roots was evaluated histologically. Mechanical hyperalgesia was detected in rats in which autologous nucleus pulposus was applied to the nerve root but not in those in which silk loops were used. Silk loops around the nerve root resulted in thermal hyperalgesia only in rats in which autologous nucleus pulposus was applied to the nerve root. Fewer large myelinated fibers were seen in the rats in which silk loops were used. Although a silk loop around the nerve root was not sufficient to produce hyperalgesia, supplemental application of autologous nucleus pulposus to the nerve root produced thermal hyperalgesia. It is possible that mechanical constriction of the nerve root alters the pain-related behavior elicited by chemical factors from the nucleus pulposus.     

Role of leukocytes in radicular pain secondary to herniated nucleus pulposus

Some studies have assessed inflammatory cells such as macrophages, lymphocytes, and neutrophils in herniated lumbar disc tissues using histologic analysis. However, there is no consensus regarding the relationships between clinical symptoms, including radicular pain and the presence of inflammatory cells. It has been shown that autologous nucleus pulposus relocated on the lumbar nerve root in rats produces time dependent and reversible mechanical hyperalgesia, which is thought to be a pain related behavior in peripheral neuropathic pain models. The purpose of this study was to determine whether leukocytes play a role in the mechanical hyperalgesia induced by the nucleus pulposus and to characterize the role of leukocytes in radicular pain attributable to lumbar disc herniation. Nitrogen mustard was used to induce and evaluate leukocytopenia in rats. Sensitivity to mechanical noxious stimuli was measured quantitatively, and inflammatory cells in granulation tissue around the nerve root were examined histologically. The nucleus pulposus produced neither mechanical hyperalgesia nor abundant inflammatory cells in rats with nitrogen mustard induced leukocytopenia. Neuropathic pain produced by the nucleus pulposus, when placed on the nerve root, may be related to inflammatory cell infiltration induced by relocation of the nucleus pulposus, rather than the nucleus pulposus itself.     

一氧化氮在神经根性疼痛中的作用

目的：探索一氧化氮(NO)在髓核突出所致的神经根性疼痛中的作用。方法：取大鼠自体尾椎髓核无压迫下放置在L4和L5神经根表面，分别在术后3d及1、2、3、4周时观察大鼠后足机械刺激和热刺激敏感性的变化，并用免疫组化方法对移植髓核中的一氧化氮合酶(NOS)进行检测．探索NO在疼痛中的作用：结果：在无明显机械压迫情况下，大鼠腰神经根上放置自体髓核可产生痛觉过敏，移植髓核组织中NOS染色阳性一结论：髓核自身是引起腰腿痛的重要原因，NO可能参与疼痛的产生.     

Comparison of neuropathic pain induced by the application of normal and mechanically compressed nucleus pulposus to lumbar nerve roots in the rat.

We studied whether applying nucleus pulposus tissue, obtained from tail intervertebral discs that had been subjected to chronic mechanical compression, to the lumbar nerve roots produces hyperalgesia, which is thought to be a pain-related behavior in the rat. An Ilizarov-type apparatus was used for immobilization and chronically applied compression of the rat tail for eight weeks. Three weeks after application of extracted nucleus pulposus tissue on the lumbar nerve roots, motor function, sensitivity to noxious mechanical stimuli was measured. Eight weeks after application of the apparatus, the instrumented vertebrae were resected and sections were stained with hematoxylin and eosin to evaluate degeneration of the intervertebral disc. Mechanical hyperalgesia observed in rats treated with the compressed nucleus pulposus tissue was greater and of longer duration than in the rats treated with normal and non-compressed discs. The nucleus pulposus in the instrumented vertebrae showed some histological degeneration. In conclusion, chronic mechanical compression of nucleus pulposus, which resulted in degeneration to some extent, enhanced mechanical hyperalgesia, which was induced by application of nucleus pulposus on the nerve root in the rat. Degenerative intervertebral discs might induce more significant pain than normal intervertebral discs.     

皮层躯体感觉诱发电位在监测腰神经根损伤中作用的研究

目的：利用大鼠髓核突出动物模型。探索皮层躯体感觉诱发电位（CSEP）的波幅和潜伏期变化是否与神经根性疼痛有关系。方法：取大鼠自体尾部的髓核无压迫下放置在L4和L5神经根上，制成髓核突出动物模型。分别在术后3d,1,2及4周观察大鼠术侧肢体机械刺激敏感性和热刺激敏感性和热刺激敏感性的变化，并引出大鼠后肢CSEP，观察术侧肢体CSEP的变化。结果：在无明显机械压迫的情况下，大鼠腰神经根上植入自体髓核可产生痛觉过敏，CSEP波幅增高。结论：髓核自身是引起腰腿痛的重要原因，CSEP波幅的增高与神经根性疼痛有一定相关性。     

一个新的椎间盘源性坐骨神经疼痛动物模型的建立

目的吸取以往神经根性疼痛动物模型的优缺点，模拟临床椎间盘突出的病理形式，建立一个新的坐骨神经痛动物模型。方法取大鼠自体尾部椎间盘组织放置在L5神经根下，造成对L5神经根的直接压迫，术后不同时间点测定大鼠后足底机械刺激疼痛阈值的变化。根据行为学结果检测脊髓背角伤害性刺激标记物c—fos蛋白的表达，并与行为学结果相对照。结果术后实验组大鼠后足底产生了一个长时程机械痛觉敏感性的升高，3周时达到峰值，然后逐渐恢复。3周时相应脊髓背角浅层中出现了c—fos蛋白的表达。结论新建立的椎间盘源性坐骨神经痛动物模型在病理机制上与临床腰椎间盘突出的产生过程相似，并且此模型能够产生一个长时程的机械痛觉过敏，因此这一模型适于用来研究临床腰椎间盘突出所致的坐骨神经痛的机制。     

Application of nucleus pulposus to the nerve root simultaneously reduces blood flow in dorsal root ganglion and corresponding hindpaw in the rat

STUDY DESIGN: An experimental study to clarify the effects of nucleus pulposus on blood flow in the dorsal root ganglion and hindpaws. OBJECTIVES: To investigate the effects of application of nucleus pulposus to nerve root on blood flow in the dorsal root ganglion and the corresponding hindpaw. SUMMARY OF BACKGROUND DATA: It has been reported experimentally that application of nucleus pulposus into the epidural space induces morphologic and functional changes in the nerve roots and induces compartment syndrome in the dorsal root ganglia. However, it has not been clarified which of these changes induces symptoms in the lower limbs. METHODS: Sixteen adult, female Sprague-Dawley rats had the left L5 nerve root and associated dorsal root ganglions exposed. Autologous nucleus pulposus was applied to the L5 nerve root, just proximal to the dorsal root ganglion (NP group). For control, the same volume of muscle tissue was applied similarly to the neural tissue (control group). Blood flow in the dorsal root ganglion, corresponding hindpaw, and the contralateral hindpaw was continuously monitored by two-channel laser Doppler flowmeter for 3 hours. After measurement of blood flow, the nerve root and dorsal root ganglion were processed for histology and evaluated by light microscope. RESULTS: Blood flow in the NP group was reduced, not only in the dorsal root ganglion, but also in the corresponding hindpaw. These reductions were statistically significant compared with the control group (P < 0.01). Edema was the principal pathologic finding seen consistently in the nerve roots and in many of the associated dorsal root ganglia from nucleus pulposus-treated animals. CONCLUSION: Application of nucleus pulposus to nerve root decreased blood flow in the dorsal root ganglion and corresponding hindpaw. These basic pathophysiologic changes are associated with compression injuries caused by herniated discs and are accepted neuropathologic mechanisms of injury associated with painful neuropathies. These acute observations in the dorsal root ganglion and the hindpaw may be important initial factors in the pathogenesis of radicular leg pain (sciatica) due to disc herniation.