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.     

Dorsal root ganglia morphologic features in patients with herniation of the nucleus pulposus: assessment using magnetic resonance myelography and clinical correlation.

STUDY DESIGN: Morphologic features of the dorsal root ganglia were investigated in patients with herniation of the nucleus pulposus by means of magnetic resonance myelography. OBJECTIVES: This study was undertaken to assess morphologic changes of the dorsal root ganglia in patients with herniation of the nucleus pulposus and to determine the relations between the morphologic features of the dorsal root ganglia and clinical features. SUMMARY OF BACKGROUND DATA: It has recently been reported that application of the nucleus pulposus to a nerve root induces edema in the rat dorsal root ganglion. Edema in the human dorsal root ganglion resulting from lumbar disc herniation has not been discussed in the literature, to the authors' knowledge. METHODS: Eighty-three consecutive patients (average age 42.1 years; range 17 to 77 years) with monoradicular symptoms were examined. Dorsal root ganglion morphologic features, i.e., indentations and swelling, were evaluated by magnetic resonance myelography. The dorsal root ganglion swelling at each level was quantitatively expressed as a ratio of the dorsal root ganglion width on the involved side to that of the contralateral side and was termed dorsal root ganglion ratio. Eighty-three uninvolved levels were chosen as controls in a randomized manner. Factors possibly contributing to the morphologic changes in the dorsal root ganglion were investigated. Neurologic symptoms, evaluated by the Japan Orthopaedic Association scoring system, were correlated to the morphologic changes. The morphologic features were followed up for 1 year after treatment in a small group of patients. RESULTS: Dorsal root ganglion indentations were always found in the narrowed intervertebral foramens. The incidence of indentations was significantly higher at the involved nerve roots (10.8%) than at the uninvolved nerve roots (4.0%) (P = 0.026). Patients with dorsal root ganglion indentations were significantly older (P = 0.0008). Leg pain scores in patients with indentations were significantly poor (P = 0.007). The dorsal root ganglion ratios were significantly higher at the involved levels than at the uninvolved levels (P = 0.001); the means +/- SD were 1.19 +/- 0.25 and 1.08 +/- 0.13, respectively. Patients with lateral herniated nucleus pulposus had significantly higher dorsal root ganglion ratios than those with central herniated nucleus pulposus (P = 0.0001); the mean ratios +/- SD were 1.48 +/- 0.32 and 1.10 +/- 0.12, respectively. A moderate positive correlation was found between dorsal root ganglion ratio and age (Pearson's correlation coefficient = 0.313). There was moderate negative correlation between the dorsal root ganglion ratio and leg pain, gait, motor, and total Japan Orthopaedic Association score (correlation coefficients were = -0.385, -0.350, -0.422, and -0.358, respectively). The dorsal root ganglion ratios were significantly diminished at 1-year follow-up (P = 0.001); the means +/- SD were 1.22 +/- 0.22 and 1.09 +/- 0.07, respectively. Indentations observed before treatment disappeared after treatment. CONCLUSIONS: Swelling and impingement in the involved dorsal root ganglion were clearly visualized by magnetic resonance myelography. The swelling and indentations were well correlated with severity of leg pain. These findings have important value in understanding the pathophysiology of the nerve roots in herniated 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.     

Clinical features of extraforaminal lumbar disc herniation based on the radiographic location of the dorsal root ganglion

STUDY DESIGN: The relations between the location of the dorsal root ganglion and pre- and postoperative symptoms were reviewed retrospectively in 27 patients who underwent radiculography and posterior discectomy. OBJECTIVES: To evaluate the clinical features and surgical outcome of extraforaminal lumbar disc herniation based on the location of dorsal root ganglion. SUMMARY OF BACKGROUND DATA: The location of dorsal root ganglia has been reported to be correlated with a variety of radicular symptoms. Extraforaminal lumbar disc herniation has several specific clinical features, one of which is severe radicular pain. However, there is no report in the literature on the association between the location of the dorsal root ganglia and the severity of the symptoms of extraforaminal lumbar disc herniation. METHODS: The radiographic location of the dorsal root ganglion of each compressed nerve root was determined by preoperative direct radiculograms. All patients were classified into the following three groups according to the location of dorsal root ganglion: intraspinal, intraforaminal, and extraforaminal. The incidences of these locations were 5 of 27 (18.5%), 15 of 27 (55.5%), and 7 of 27 (25.9%), respectively. The relation between the location of the dorsal root ganglion and clinical parameters such as the level of the compressed nerve root, the degree of limitation on straight leg raising test, the severity of the pre- and postoperative subjective symptoms (leg pain, low back pain, and walking capacity), clinical signs (sensory and motor disturbance), and the recovery rate were investigated. RESULTS: The degree of limitation on the straight leg raising test in the extraforaminal group tended to be low, compared with that in the intraspinal and intraforaminal groups. Low back pain in the extraforaminal group was more severe than that in the intraspinal and intraforaminal groups. Preoperative leg pain in the extraforaminal group was significantly more severe that that in the intraspinal group, and the walking capacity in the extraforaminal group tended to be lower than that in the intraspinal and intraforaminal groups. No significant differences were found between the location of dorsal root ganglion and the preoperative sensory or motor disturbance and surgical outcomes. CONCLUSION: The location of the dorsal root ganglion might influence the severity of radicular symptoms (pain and walking distance tolerance) in patients with extraforaminal lumbar disc herniation.     

Prevention of compartment syndrome in dorsal root ganglia caused by exposure to nucleus pulposus

STUDY DESIGN: An experimental study to clarify the effects of pentoxifylline, as an anti-tumor necrosis factor-alpha therapy on endoneurial fluid pressure in the dorsal root ganglion using an animal model of herniated nucleus pulposus. OBJECTIVES: To investigate the effects of anti-tumor necrosis factor-alpha therapy to nucleus pulposus-induced nerve root/dorsal root ganglion changes. SUMMARY OF BACKGROUND DATA: It has been reported experimentally that application of nucleus pulposus into epidural space induces morphologic and functional changes in the nerve roots and induces compartment syndrome in the dorsal root ganglia. Tumor necrosis factor-alpha has been considered a key pathogenic factor in the initiation and maintenance of neuropathic pain states. METHODS: A total of 11 adult, female Sprague-Dawley rats had their left L5 nerve roots and associated dorsal root ganglions exposed. Autologous nucleus pulposus was applied to the L5 nerve root just proximal to the dorsal root ganglion. A piece of Spongel (Yamanouchi Pharmaceutical Co., Tokyo) containing 20 microL of 1000 microg/mL pentoxifylline was applied with the nucleus pulposus (NP+PTX group). In control animals nucleus pulposus was applied with a piece of Spongel containing 20 microL of physiologic saline solution in a similar fashion (NP+PS group). Endoneurial fluid pressure was recorded with a servo-null micropipette system using glass micropipettes with tip diameters of 4 microm. Endoneurial fluid pressure in the dorsal root ganglion was measured before and 3 hours after application of test substances. After measurement of endoneurial fluid pressure, the nerve root and dorsal root ganglion were processed for histology and evaluated by light microscope. RESULTS: Values of endoneurial fluid pressure before application of test substances were as follows: 2.4 +/- 1.2 cm H2O in the NP+PS (control) group and 1.8 +/- 0.4 cm H2O in the NP+PTX group. There was no statistically significant difference between these two pretreatment measurements. However, values of endoneurial fluid pressure after application were as follows: 8.6 +/- 1.8 cm H2O in the NP+PS group and 2.9 +/- 0.8 cm H2O in the NP+PTX group. Values of endoneurial fluid pressure in the NP+PTX group were significantly lower compared with the NP+PS group. Histologic examination consistently showed only a slight degree of edema evident in the NP+PTX group compared with the NP+PS group. CONCLUSION: Pentoxifylline, an anti-tumor necrosis factor-alpha drug, prevented the dorsal root ganglion compartment syndrome caused by topical application of nucleus pulposus. Anti-inflammatory cytokine therapy may become an effective treatment of sciatica due to disc herniation.     

Effects of lidocaine on blood flow and endoneurial fluid pressure in a rat model of herniated nucleus pulposus

STUDY DESIGN: An experimental study was conducted to evaluate the effects of lidocaine on nucleus pulposus-induced pathophysiologic changes. OBJECTIVES: To investigate the effects of lidocaine on blood flow in the hind paws and endoneurial fluid pressure in the dorsal root ganglia in a rat model of herniated nucleus pulposus, and to clarify the therapeutic mechanisms of nerve root infiltration. SUMMARY OF BACKGROUND DATA: It has been shown experimentally that application of nucleus pulposus to the nerve roots increases endoneurial fluid pressure and decreases blood flow in the dorsal root ganglia and the corresponding hind paw. These changes are thought to be an important pathogenic mechanism associated with sciatica caused by disc herniation. Nerve root infiltration is one of the nonoperative effective therapies for radiculopathy caused by disc herniation. However, the therapeutic mechanisms still are unknown. METHODS: For this study, 21 Sprague-Dawley rats were used. Autologous nucleus pulposus was applied to the nerve root with a piece of Spongel containing lidocaine (lido group) or physiologic saline solution (control group). In Series 1 of this study (Blood Flow in the Hind Paw), blood flow in the corresponding hind paws was monitored continuously using a laser Doppler flowmeter before application of the test solutions, and every 5 minutes thereafter for an additional 3 hours in both the control (n = 5) and lido (n = 5) groups. In Series 2 of this study (Endoneurial Fluid Pressure in the Dorsal Root Ganglion), endoneurial fluid pressure was recorded with a servo-null micropipette system using glass micropipettes before and 3 hours after application of the test solutions in both the control (n = 6) and lido (n = 5) groups. After measurements, dorsal root ganglia were assessed for histology. RESULTS: In Series 1, blood flow in the corresponding hind paw in the control group showed significant reduction as compared with that of the Lido group, starting about 90 minutes after application (P < 0.01-0.05). Hind paw blood flow in the lido group did not show any reduction during measurements. In Series 2, the value of endoneurial fluid pressure in the lido group 3 hours after application was significantly lower than in the control group (P < 0.01). Interstitial (endoneurial) edema in the dorsal root ganglion in the lido group appeared to be qualitatively less than in the control group. CONCLUSIONS: The data indicate that lidocaine reduces the pathophysiologic changes in the dorsal root ganglion and hind paws induced by nucleus pulposus. These effects of lidocaine may relate to the mechanisms underlying the therapeutic effects of nerve root infiltration.     

Roles of thromboxane A2 and leukotriene B4 in radicular pain induced by herniated nucleus pulposus.

Biologically active substances, such as prostaglandins, thromboxanes, and leukotrienes, which are metabolites involved in the arachidonic acid cascade, are detected in herniated disc samples obtained from patients with lumbar disc herniation. However, little is known concerning the relationships between these substances and clinical symptoms such as radicular pain. Thromboxane A2 (TXA2) induces not only potent platelet aggregation, but also blood vessel contraction. Leukotriene B4 (LTB4), a potent chemotactic agent, plays a role in inflammatory reactions by recruiting neutrophils and lymphocytes. The purpose of this study was to examine the roles of TXA2 and LTB4 in the hyperalgesia induced by application of nucleus pulposus to the lumbar nerve root in the rat. TXA2 synthetase inhibitor and LTB4 receptor antagonist, which were injected into the epidural space, decreased mechanical hyperalgesia at both three and seven days after epidural injection. There were no significant differences in sensitivity to noxious thermal stimuli following application of the nucleus pulposus or an epidural injection. Epidural injection of LTB4 receptor antagonist and/or TXA2 synthetase inhibitor may attenuate the painful radiculopathy due to lumbar disc herniation. In conclusion, our findings suggest that TXA2 and LTB4 may play significant roles in mechanical hyperalgesia induced by autologous nucleus pulposus.     

腰椎间盘突出症非对称性下肢放射痛的原因及治疗

目的：探讨腰椎间盘突出症导致非对称性下肢放射痛的原因及治疗。方法：回顾性分析了手术治疗的53例病人。其中全椎板切除39例，扩大半椎板切除14例。结果：对侧侧隐窝狭窄23例，游离髓核组织压迫对侧神经根24例，脊髓丘脑侧束内存在不交叉纤维6例。结论：对侧侧隐窝狭窄和游离髓核组织压迫对侧神经根是导致非对称性下肢放射痛的主要原因，手术日寸要注意对对侧侧隐窝减压，除游离的髓核组织。只有确定无导致对侧下肢放射痛的原因后。才能确定为脊髓丘脑侧束内存在不交叉纤维。     

腰椎间盘源性疼痛机理的临床研究

目的 :分析腰椎间盘突出症病人的临床症状、体征与椎间盘和神经根大体病理形态改变的关系 ,临床症状、体征和椎间盘突出类型与髓核中炎症介质 (磷脂酶A2 )水平的关系以及临床症状、体征和椎间盘突出类型与脑脊液 (以下简称CSF)中神经肽类递质变化的关系。从临床角度探讨腰椎间盘突出症疼痛机理。材料与方法 :分析161例腰椎间盘突出病人的髓核突出类型及神经根病理形态改变与腰腿痛程度的关系 ;分析 2 0例腰椎间盘髓核组织中磷脂酶A2 活性水平与神经根性疼痛程度的关系 ;3 1例腰椎间盘突出症病人脑脊液中P物质和降钙素基因相关肽含量与神经根性疼痛程度进行比较。结果 :①腰椎间盘的膨出、突出、脱出和脱出游离各组之间无疼痛程度的统计学显著差异。而神经根呈急性炎症反应的病人中重度疼痛高达 80 % (P <0 .0 1)。②腰椎间盘突出症病人椎间盘髓核中磷脂酶A2 活性显著高于自身血液中和健康人椎间盘髓核中磷脂酶A2 活性水平 ,腰椎间盘突出症病人的腰腿痛程度与其髓核中磷脂酶A2 活性明显相关。③腰痛病人脑脊液中P物质和降钙素基因相关肽水平高于正常对照组 ,并与疼痛等级有关。结论 :①腰椎间盘突出物的病理形态和对神经根的机械压迫与其引起的临床疼痛症状和神经根体征无明确关系 ,而神经根性疼痛与局部     

The effects of a 5-HT2A receptor antagonist on blood flow in lumbar disc herniation : application of nucleus pulposus in a canine model

Blood vessel clots are found around the nerve root in patients with lumbar disc herniation. Thrombosis formation in the experimental application of nucleus pulposus to the nerve root has been shown in histological studies. In addition, reduction of blood flow and nerve conduction velocity are induced by the application of nucleus pulposus, which mimics lumbar disc herniation. In patients with lumbar disc herniation, nerve root block, which is thought to increase nerve blood flow, improves radiculopathy. 5-HT_2A receptor antagonists are used in chronic arterial occlusive diseases to improve blood flow and have been reported to work as well as nonsteroidal anti-inflammatory drugs in improving radiculopathy due to lumbar disc herniation in clinical studies. This study investigated the effects of a 5-HT_2A receptor antagonist on blood vessel diameter and blood flow in a canine experimental model of lumbar disc herniation. A total of 13 dogs were used. The animals were divided into three experimental groups and surgery was performed 1 week before measurements. In the nucleus pulposus group (NP; n = 5), the nucleus pulposus was applied to the nerve roots from the ventral side. In the sham group (n = 5), nucleus pulposus was not applied. In the naïve group (n = 3), the animals did not undergo surgery. Measurements of vessel diameter and blood flow were done before and after administration of saline and drugs. The diameters and blood flow volume of the observed blood vessels were measured on video-recordings every 10 min for 65 min. In all groups, vessel diameter and blood flow did not change before or after administration of saline. In the NP and sham groups, vessel diameter and blood flow increased significantly after administration of 5-HTRA compared with the naïve group. 5-HTRA improved blood vessel diameter and blood flow in the nerve roots inflamed by the application of nucleus pulposus but not in the intact nerve roots. 5-HTRA might be a potential agent to improve blood flow in the nerve roots of patients with lumbar disc herniation.     

The effect of age on inflammatory responses and nerve root injuries after lumbar disc herniation: an experimental study in a canine model

STUDY DESIGN: An experimental investigation on the effect of age on pathologic events surrounding the herniated disc and at the adjacent nerve root. OBJECTIVES: To investigate the role of age on the inflammatory responses and nerve root damage surrounding a sequestered lumbar disc fragment using a dog model. SUMMARY OF BACKGROUND DATA: Lumbar disc herniation is manifested in patients by variable clinical findings, natural history, and resorption phenomena in which the variability is particularly noted among patients with different ages. There are no previous reports on the effect of age on pathologic events induced by the herniated disc. METHODS: Six beagle dogs, including two animals of each age group of 6, 12, and 24 months (human equivalent ages of 10, 15, and 24 years), were used in this study. The dogs underwent L4-L5, L5-L6, and L6-L7 laminotomy and discectomy under general anesthesia. An autologous intervertebral disc from the tail was divided into anulus fibrosus and nucleus pulposus fragments. The anulus fibrosus and nucleus pulposus fragments were placed in the anterolateral epidural space of L5-L6 and L6-L7, respectively. The L4-L5 discectomy site served as a control. Dogs were killed at 12 weeks after surgery. The lumbar spine was removed en bloc, and histologic sections were prepared consecutively and examined. RESULTS: In the nucleus pulposus group at L6-L7, neovascularity, and intensive infiltration of lymphocytes, macrophages, and fibroblasts were observed surrounding the nucleus pulposus fragment in the 24-month-old group only. Degenerative changes of the nerve root fibers were observed in the 24-month-old group only. In the control and anulus fibrosus groups at L4-L5 and L5-L6, there were no marked inflammatory reactions in all age groups. The nerve root fibers around the anulus fibrosus were normal in all age groups. CONCLUSIONS: There is an effect of age on the inflammatory response and nerve root injury caused by the herniated disc. The apparent neuroprotective mechanism in the young animal, and the apparent inflammatory and resorption changes of the nucleus pulposus fragment in the older animal are quite intriguing.     

2000 Volvo Award winner in basic science studies: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats

STUDY DESIGN: This study tested the hypothesis that the 17-kDa form of tumor necrosis factor-alpha is the pathophysiologic agent expressed by herniated nucleus pulposus in vivo that is primarily responsible for the histologic and behavioral manifestations of experimental sciatica associated with herniated lumbar discs. OBJECTIVE: The authors determined the molecular weight and concentration of active tumor necrosis factor-alpha in rat herniated disc and used exogenous tumor necrosis factor-alpha at the same molecular weight to study its neuropathologic effect on rat nerve root and dorsal root ganglion preparations in vivo. SUMMARY OF BACKGROUND DATA: Expressed by herniated nucleus pulposus in culture, tumor necrosis factor-alpha causes neuropathologic injury in nerve roots and neuropathic pain states in which mechanical allodynia is seen in response to peripheral stimuli. METHODS: Western blotting was used to identify the molecular weight of the operative tumor necrosis factor-alpha protein form, and measures of optical density were used for semiquantitative determination of concentration. Plastic-embedded nerve roots and dorsal root ganglion were used for neuropathologic evaluation, and von Frey stimulation was used to quantify mechanical allodynia. RESULTS: The 17-kDa form of tumor necrosis factor-alpha is expressed by herniated nucleus pulposus at a concentration of approximately 0.48 ng per herniated rat lumbar disc. Exogenous tumor necrosis factor-alpha applied in vivo to rat nerve roots produced neuropathologic changes and behavior deficits that mimicked experimental studies with herniated nucleus pulposus applied to nerve roots. CONCLUSIONS: The data reinforce other evidence that tumor necrosis factor-alpha is involved in mechanisms of neuropathic pain.     

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。     

Herniated lumbar disc material as a source of free glutamate available to affect pain signals through the dorsal root ganglion

STUDY DESIGN: Combined prospective human cohort and prospective controlled animal model. OBJECTIVES: To determine whether free glutamate is available in herniated disc material in concentrations sufficient to diffuse to glutamate receptors and affect the activity of neurons in the dorsal root ganglion that may transmit pain information. SUMMARY OF BACKGROUND DATA: The severity of lumbar radicular pain cannot be fully explained by physical pressure on nerve roots or ganglions. In experimental models, inflammatory processes are relatively modest under conditions of disc herniation. The hypothesis for the current study was that the proteoglycan link and core proteins, which contain high fractions of acidic amino acids, may be a source of glutamate when enzymatically degraded in an environment without glutamate reuptake systems. Glutamate would be free to diffuse to the dorsal root ganglion to affect glutamate receptors. METHODS: Disc material was harvested during surgery from herniated and nonherniated portions in patients undergoing elective lumbar disc surgery and subjected to immunohistochemistry and high-performance liquid chromatography for assessment of the presence of extracellular disc matrix glutamate. Miniosmotic pumps with differing concentrations of radiolabeled glutamate based on human data were implanted in the rat epidural space for 72 hours and dorsal root ganglion (DRG) in the region were harvested. RESULTS: Densitometry of disc matrix demonstrated immunohistochemical evidence for significant extracellular glutamate (P < 0.002). High performance liquid chromatography showed significant concentrations of glutamate in disc material and significantly more in herniated than in nonherniated disc material (P < 0.05). Significant radiolabeling of the dorsal root ganglion after epidural glutamate infusion was found at concentrations two orders of magnitude below measured disc glutamate levels. Autoradiography demonstrated radiolabeling of adjacent DRG. CONCLUSIONS: Glutamate originating from degenerated disc proteoglycan may diffuse to the dorsal root ganglion and effect glutamate receptors. Consideration may be given to treating disc radiculopathy with epidural glutamate receptor antagonists.     

Nitric oxide as a mediator of nucleus pulposus-induced effects on spinal nerve roots.

Nerve root dysfunction and sciatic pain in disc herniation are considered to be caused by mechanical compression and related to the presence of nucleus pulposus in the epidural space. Autologous nucleus pulposus has been shown to induce endoneural edema and to decrease nerve-conduction velocity in spinal nerve roots in experimental disc herniation models, and inflammatory mediators have been suggested to be involved in these mechanisms. Nitric oxide, a potent inflammatory mediator, is implicated in vasoregulation, neurotransmission, and neuropathic pain. Nitric oxide synthesis can be induced by different cytokines, e.g., tumor necrosis factor-alpha, which recently was shown to be of pathophysiological importance in experimental disc herniation. The enzyme nitric oxide synthase mediates the production of nitric oxide. Three series of experiments were performed in rat and pig disc herniation models to (a) investigate nitric oxide synthase activity in spinal nerve roots after exposure to autologous nucleus pulposus and (b) evaluate the effects of systemic treatment with aminoguanidine, a nitric oxide synthase inhibitor, on vascular permeability and nerve-conduction velocity. In a disc herniation model in the rat, calcium-independent nitric oxide synthase activity was measured in nerve roots exposed to nucleus pulposus; however, no nitric oxide synthase activity was detected in nerve roots from animals that underwent a sham operation, reflecting increased inducible nitric oxide synthase activity. In nucleus pulposus-exposed spinal nerve roots in the pig, the edema was less severe after systemic aminoguanidine administration than without aminoguanidine treatment. Aminoguanidine treatment also significantly reduced the negative effect of nucleus pulposus on nerve-conduction velocity in spinal nerve roots in the pig. These results demonstrate that nucleus pulposus increases inducible nitric oxide synthase activity in spinal nerve roots and that nitric oxide synthase inhibition reduces nucleus pulposus-induced edema and prevents reduction of nerve-conduction velocity. Furthermore, the results suggest that nitric oxide is involved in the pathophysiological effects of nucleus pulposus in disc herniation.     

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.     

临床症状与髓核突出左右不一致的腰椎间盘突出症的诊治

目的探讨腰椎间盘突出症导致非对称性下肢放射痛的可能原因及术式的选择。方法25例经SCT、MRI检查证实为突出侧与临床症状侧别左右不一致的腰椎间盘突出症患者，均行手术治疗，其中14例行双侧开窗减压探查髓核摘除术，11例仅行突出侧开窗术。结果影像学上髓核突出侧别与术中所见相吻合，但该侧神经根未见到明显压迫或炎性水肿等病理表现；而症状侧无髓核突出，5例神经根未发现异常表现，9例存在不同程度的炎性水肿，其中6例探查发现神经根与对侧髓核不同程度粘连。术后所有患者症状均得到缓解，经过1～5年（平均2．4年）的随访，均无复发。结论SCT结合MRI检查有助于此类腰椎间盘突出症的明确诊断。纤维环无破裂的突出型腰椎间盘突出症，单纯突出侧减压可以获得较好的治疗效果；纤维环破裂的游离型及脱出型腰椎间盘突出症，宜同时行对侧开窗探查。     

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.     

经皮内窥镜治疗腰椎间盘突出症的并发症及其处理

目的 总结经皮内窥镜腰椎间盘切除术( PELD)治疗腰椎间盘突出症中出现的并发症,探讨其处理对策.方法 2002年7月至2010年10月采用PELD治疗腰椎间盘突出症患者689例,男性448例,女性241例;年龄13 ～84岁,平均39.8岁.单间隙椎间盘突出669例,双间隙椎间盘突出19例,三间隙椎间盘突出l例.中央型突出66例,旁中央型365例,外侧型242例,极外侧型10例,游离型6例.观察术中和术后并发症及其处理.结果 术中髓核部分残留压迫神经根5例,2例术中改行开窗髓核切除术,2例二期行开窗髓核切除术,1例二期行经椎间孔腰椎体间融合术(TLIF);神经根纤维束部分损伤2例,术后3～6个月内完全恢复;硬脊膜破裂2例,给予缝合皮肤伤口后痊愈.689例患者随访6～96个月,平均33个月.出现椎间隙感染7例,1例保守治疗,4例给予经皮穿刺置管冲洗引流持续局部应用抗生素,2例行后路开窗感染腰椎间盘清除术,均痊愈;术后复发6例,4例患者再次行PELD术,2例患者采用TLIF治疗,术后症状缓解;术后神经根性痛觉过敏和灼样神经根痛19例,经过止痛药物、神经营养药及物理治疗后好转;腰椎管狭窄症行单个节段的PELD术,效果不佳,二期行多节段TLIF治疗10例.结论 术中主要并发症有髓核部分残留压迫神经根、神经根纤维束部分损伤、硬脊膜破裂;术后主要并发症有椎间隙感染、复发、神经根性痛觉过敏和灼样神经根痛等.严格的适应证选择、无菌、熟练操作及术后康复锻炼可以减少并发症的发生.