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.     

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.     

Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced thrombus formation, intraneural edema, and reduction of nerve conduction velocity: possible implications for future pharmacologic treatment strategies of sciatica

STUDY DESIGN: The possibility to prevent nucleus pulposus-induced functional and structural nerve root injury by selective tumor necrosis factor-alpha inhibition was assessed in an experimental model in the pig spine. OBJECTIVE: The objective of the study was to evaluate the role of tumor necrosis factor-alpha in the mediation of nucleus pulposus-induced nerve injury by using selective inhibition. SUMMARY OF BACKGROUND DATA: The cytokine tumor necrosis factor-alpha has been suggested to play a key role in the nerve root injury induced by local application of nucleus pulposus. However, previous studies have not been able to distinguish the effects between tumor necrosis factor-alpha and other disc-related cytokines because of the use of nonspecific cytokine inhibition. METHODS: Autologous nucleus pulposus was harvested from a lumbar disc and applied to the porcine sacrococcygeal cauda equina. The pigs were simultaneously treated with two selective tumor necrosis factor-alpha inhibitors (etanercept n = 8 and infliximab n = 5), a heparin analogue (enoxaparin n = 5) or saline for control (n = 5). After 7 days the nerve conduction velocity over the application zone was determined and samples of the exposed nerve roots were collected for light microscopic evaluation. RESULTS: The two tumor necrosis factor-alpha inhibitors prevented the reduction of nerve conduction velocity and also seemed to limit the nerve fiber injury, the intracapillary thrombus formation, and the intraneural edema formation. However, treatment with enoxaparin did not seem to be different from control regarding reduction of nerve conduction velocity or histologic changes. CONCLUSIONS: The data clearly indicate that tumor necrosis factor-alpha is involved in the basic pathophysiologic events leading to nerve root structural and functional changes after local application of nucleus pulposus. The study therefore provides a basic scientific platform with potential clinical implications regarding the use of anti-tumor necrosis factor-alpha medication as treatment in patients with disc herniation and sciatica.     

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。     

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.     

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.     

Lumbar disc herniation. Computed tomography scan changes after conservative treatment of nerve root compression.

In 21 patients with computed tomography-diagnosed lumbar herniated nucleus pulposus, nerve root pain resolved after conservative treatment. A subsequent computed tomography scan was performed 6 months or more after presentation. This follow-up computed tomography scan was compared with the initial one. A definite decrease in size of the herniated nucleus pulposus was observed in 14 patients: disappearance in 5, obvious decrease in 5, and moderate decrease in 4. No definite change was observed in seven patients. Major computed tomography scan changes occurred significantly more frequently in large herniated nucleus pulposus than in small ones (p. less than 0.05). This study suggests that large lumbar herniated nucleus pulposus can decrease and even disappear in some patients treated successfully with conservative care.     

Effect of nucleus pulposus on the neural activity of dorsal root ganglion

STUDY DESIGN: This study was designed to investigate, using neurophysiologic techniques in an in vivo rat model, the effect of application of nucleus pulposus to the nerve root on the neural activity of the dorsal root ganglion and the corresponding receptive fields. OBJECTIVES: To assess a further role of the dorsal root ganglion in mechanisms of radicular pain in lumbar disc herniation. SUMMARY OF BACKGROUND DATA: It has been suggested that the epidural application of autologous nucleus pulposus without mechanical compression causes nerve root inflammation and related radicular pain in lumbar disc herniation. Concerning the dorsal root ganglion, its mechanical hypersensitivity and potential for generating ectopic discharges have been reported. However, the effect of autologous nucleus pulposus on the dorsal root ganglion is uncertain. METHODS: In adult Sprague-Dawley rats spontaneous neural activity was recorded from the surgically exposed L5 dorsal root using electrophysiologic techniques, and the mechanosensitivity of L5 dorsal root ganglia and corresponding receptive fields on the hind paw were measured using calibrated nylon filaments. Autologous nucleus pulposus from the tail or fat was implanted at the L5 nerve root. Neural activity was monitored for 6 hours. RESULTS: Spontaneous neural activity in the nucleus pulposus group gradually increased and showed significant differences compared with the fat group from 2.5 to 6 hours after exposure. The mechanosensitivity of the dorsal root ganglia showed significant increases compared with the fat group. CONCLUSIONS: After application of nucleus pulposus to the nerve root, the dorsal root ganglion demonstrated increased excitability and mechanical hypersensitivity. These results suggest that nucleus pulposus causes excitatory changes in the dorsal root ganglion.     

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.     

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。     

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.     

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.     

临床症状体征与影像学检查分离的腰椎间盘突出症的发生机制研究进展

临床会出现少数症状体征与影像学检查结果不相符的腰椎间盘突出症患者,而单纯用传统的突出髓核直接机械压迫刺激神经根的理论不能解释这种反常的腰椎间盘突出症。腰椎间盘髓核的突出与患者临床症状体征的出现受多因素、多环节的影响,脊神经根的间接性机械压迫与神经根牵张效应为主要因素,而反常症状体征的产生往往与突出的髓核自身位置的迁移、神经系统对信息的传递以及髓核与硬膜囊或神经根的相互作用密切相关。此外,突出的髓核组织所继发的局部微循环、炎症改变,相应节段的骨质增生退变和腰椎应力姿势改变诱发此类反常腰椎间盘突出症患者出现多样性的症状体征。同时,一些患者还存在神经或椎体的先天性发育异常,并可能出现影像学检查上的误诊或漏诊。突出髓核对硬膜囊以及周围神经根之间的确切相互作用机制及其继发的局部病理生理、生物力学改变,病变责任节段的确定以及如何克服影像学检查的局限性需进一步研究。     

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.     

Somatosensory-evoked potentials in lumbar nerve root decompression

The adequacy of decompression of nerve roots is determined by direct visual observations and by correlation with roentgenograms of the pathological lesion. The usefulness of additional evidence of adequate neural decompression from intraoperative somatosensory-evoked potential (SEP) data was tested in 41 cases of a herniated intervertebral disc (27 patients) or spinal stenosis (14 patients). Postoperative observations at three weeks and three months were evaluated by intraoperative observation of decreased latency and/or increased amplitude of SEP recordings. In patients with unilateral or asymmetrical bilateral radiculopathy, the asymptomatic or less-affected leg acted as a control in the study. Successful function correlated significantly with intraoperative changes in latency toward normal in the more-affected leg, whether the lesion was herniated nucleus pulposus or spinal stenosis. Intraoperative physiological testing (SEP) is valuable for determining the adequacy of lumbar nerve root decompression and for the prediction of the successful relief of symptoms.     

Epidural injection of cyclooxygenase-2 inhibitor attenuates pain-related behavior following application of nucleus pulposus to the nerve root in the rat.

Cyclooxygenase-2 (COX-2), the inducible isoform of COX, has been identified as the key enzyme to regulate prostaglandin E2 synthesis in inflammatory conditions. Although it has been reported that COX-2 is present in herniated disc samples obtained from patients, little is known concerning the relationships between COX-2 and painful radiculopathy. The purpose of this study was to evaluate whether epidural injection of COX-2 inhibitor abolishes hyperalgesia induced by nucleus pulposus, which is a pain-related behavior in the rat. Rats, in which nucleus pulposus was relocated on the nerve root, exhibited evidence of mechanical hyperalgesia. Epidural injection of COX-2 inhibitor resulted in decrease in mechanical hyperalgesia 1 h, 3 and 7 days after the epidural injection of COX-2 inhibitor (0.1 mg/kg SC-'236 dissolved in the vehicle). There were no significant differences in sensitivity to thermal noxious stimuli after either application of the nucleus pulposus or epidural injections. These results suggest that prostaglandins and thromboxane, which are produced by COX-2 in inflammatory cells, appear to be related to the inflammatory process produced by application of nucleus pulposus to the nerve root. It is possible that COX-2 plays a significant role in painful radiculopathy following herniated nucleus pulposus.     

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.     

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.