Shoji Yabuki

Incision of the anulus fibrosus induces nerve root morphologic, vascular, and functional changes : An experimental study

Study Design The effects on nerve root structure, vasculature, and function after incision of the adjacent disc was studied in a dog model. Objectives To see if only incision of the disc per se is sufficient for inducing similar changes. Summary of Background Data It is well known that nucleus pulposus will induce nerve root structural and functional changes in experimental situations. In these previous studies, relatively large amounts of nucleus pulposus were applied. Methods The left L7 nerve root was exposed and mobilized in 10 dogs. In five dogs, the adjacent L6‐L7 disc was incised, and in five other dogs, the disc was not incised. After 7 days, nerve conduction velocity was recorded, and specimens were obtained for histologic evaluation. Results The nerve conduction velocity was significantly lower in the incision group (13 ± 14 m/sec) compared with the nonincision group (73 ± 5 m/sec). Structural changes of the axons were more pronounced in the incision group, however, the degree and distribution was too limited to fully account for the neurophysiologic reactions observed. There also were obvious signs of capillary stasis with an increased number and diameter of the intraneural capillaries in the incision group. Conclusions The present study indicated that incision of the anulus fibrosus is sufficient to induce significant morphologic and functional changes and that vascular mechanisms may be of importance for the observed changes. These experimental data suggest that leakage of nucleus pulposus material from anular tears, with injury to adjacent nerve roots, might be one pathophysiologic mechanism in patients with low back pain and sciatica but with no radiologic or surgical evidence of disc herniation.

Back muscle injury after posterior lumbar spine surgery. Topographic evaluation of intramuscular pressure and blood flow in the porcine back muscle during surgery.

Study Design Intramuscular pressure and blood flow of the back muscles were evaluated topographically during posterior lumbar spine surgery. The topographic damage of the back muscle after surgery was studied. Objective To investigate the relationship between intramuscular pressure or blood flow during posterior lumbar surgery and the back muscle injury after surgery. Summary of Background Data Iatrogenic back muscle injury in an animal and human model has been reported previously. Changes of intramuscular pressure and blood flow during surgery might be related to the muscle injury. No previous study on this issue has been published. Methods The contact pressure between the retractor blade and muscle tissue was monitored in 10 pigs during posterior surgery of the lumbar spine. On one side, intramuscular pressure at 5, 10, and 20 mm lateral to the retractor and on the other side blood flow of the back muscle at 5 and 20 mm during surgery were measured. Histologic changes of the back muscle at 5, 10, and 20 mm to the midline were evaluated 3 hours after surgery. Results The contact pressure decreased exponentially with time. Intramuscular pressure 5 mm lateral to the retractor was 114 ± 31 mm Hg and was significantly higher than at 10 mm and 20 mm. Blood flow markedly decreased during surgery and recovered incompletely after releasing the retractor at 5 mm and 20 mm lateral to the retractor. Blood flow at 5 mm was significantly lower than at 20 mm throughout surgery. The muscle damage 3 hours after surgery was more severe near the retractor blade. Conclusions The back muscles were exposed to pathophysiologic condition by a retractor during posterior lumbar spine surgery. External compression by a retractor increases intramuscular pressure to levels that impede local muscle blood flow. The muscle degeneration after surgery could be explained by direct mechanical damage and by the increased intramuscular pressure of muscle tissue by the retractor.

An anatomic study of the sacral hiatus : a basis for successful caudal epidural block

Study DesignAn anatomic study of the sacral hiatus using isolated sacra. ObjectivesTo clarify the anatomic variations of the sacral hiatus using the bony landmarks of the sacrum for improving the reliability of caudal epidural block (CEB). Background DataThe CEB has been widely used for the diagnosis and treatment of lumbar spinal disorders. The reliability of CEB is 70%–80% in the literatures. The cause of failure of CEB may depend on anatomic basis. MethodsA total of 92 isolated sacra were used in this study. The bony landmarks were sacral hiatus and sacral cornua. Morphologic types of the sacral hiatus were classified using these landmarks. Also, location of the apex of sacral hiatus, diameter of the sacral canal at the apex of sacral hiatus, and the distance between bilateral cornua were measured. Two orthopedic surgeons performed measurements independently. ResultsFourty-two percent of the cases have both hiatus and cornu. Four percent of the cases showed the absent hiatus. The apex of sacral hiatus existed at the level of S4 vertebrae in 64% of the cases. The average diameter of the sacral canal was 6.0 ± 1.9 mm. The average distance of bilateral sacral cornua was 10.2 ± 0.35 mm. There were closed hiatus in 3% of cases. ConclusionsThe sacral hiatus has anatomic variations. Understanding of these variations may improve the reliability of CEB.

The effects of normal, frozen, and hyaluronidase-digested nucleus pulposus on nerve root structure and function.

Study design. Autologous nucleus pulposus was modified and applied to the cauda equina in pigs. Histology and neurophysiology were assessed after 7 days. Objectives. To assess if alterations of the nucleus pulposus would change the degree and distribution of the nerve injury induced by autologous nucleus pulposus. Summary of background data. It was reported recently that nucleus pulposus may induce structural and functional changes in nerve roots after epidural application. The basic mechanisms causing these changes are not fully understood. Methods. Nucleus pulposus was harvested from lumbar discs and submitted to either of three treatments; 37 C for 24 hours (n = 5), −20 C for 24 hours (n = 5), or digestion by hyaluronidase for 24 hours (n = 6). In two additional pigs, nucleus pulposus was applied just after harvest as a control to verify previous observations. After 7 days, nerve conduction velocity was recorded, and specimens were processed for blinded light microscopic assessment. Results. When nucleus pulposus was applied just after harvest, or when it had been kept at 37 C or digested by hyaluronidase for 24 hours, there was a significant reduction in nerve conduction velocity similar to previous observations. When nucleus pulposus had been kept at −20 C for 24 hours, however, there was no reduction in conduction velocity. There were no apparent differences between the groups at the histologic assessment. Staining of the nucleus pulposus showed that the cells in the nucleus pulposus exposed to −20 C were lysed, whereas the cells in the nucleus pulposus treated by the two other methods were mainly unaffected. Conclusions. Because freezing of the nucleus pulposus probably kills the cells but does not affect other components, one may assume that the biologic effects induced by the nucleus pulposus may be related to its cell population.

Effects of neutralizing antibodies to tumor necrosis factor-alpha on nucleus pulposus-induced abnormal nociresponses in rat dorsal horn neurons.

Study Design. The effect of an anti–tumor necrosis factor alpha (anti-TNF&agr;) antibody on abnormal discharges caused by application of nucleus pulposus to the nerve root was investigated in an electrophysiologic study. Objectives. To assess whether inhibition of TNF&agr; can reduce nucleus pulposus–induced abnormal discharges. Summary of Background Data. It has been shown that TNF&agr;, a proinflammatory cytokine, is a key pathogenic factor in the development of nucleus pulposus–induced abnormal discharges as a pain sensation. However, the electrophysiologic mechanisms involved in sciatica after disc herniation still have not been elucidated. Methods. Extracellular activities of wide-dynamic-range neurons were assessed in 21 rats. Autologous nucleus pulposus harvested from the tail was applied to the L5 nerve root. The animals were simultaneously treated with antibodies to TNF&agr; (anti-TNF + nucleus pulposus group) and with phosphate-buffered saline (nucleus pulposus group). As a control (control group), a similar volume of muscle was applied to the nerve root with phosphate-buffered saline. Responses of wide-dynamic-range neurons to noxious and innocuous stimuli were examined for 2 hours. Results. Discharges evoked during noxious stimulation and discharges after withdrawal of stimulation in the nucleus pulposus group were significantly higher than those in the control group (P < 0.05). In the anti-TNF + nucleus pulposus group, discharges after withdrawal of stimulation were remarkably inhibited, as compared with those of the nucleus pulposus group (P < 0.05). However, evoked discharges during stimulation apparently were not inhibited. Responses to innocuous stimulation did not change throughout the measurements. Conclusions. These data indicate that application of TNF&agr; antibodies to the nerve root partially prevents the nucleus pulposus–induced abnormal nociresponses. Therefore, anti-TNF&agr; treatment may have a therapeutic effect on sciatica after lumbar disc herniation.

Pathomechanisms of nerve root injury caused by disc herniation: an experimental study of mechanical compression and chemical irritation.

Study Design. An electrophysiologic and histologic study on nerve roots after mechanical compression and/or local application of nucleus pulposus (NP) was performed. Objective. To assess the effects of mechanical compression and/or chemical irritation caused by NP. Summary of Background Data. It has been shown that application of NP to nerve roots without compression induces histologic and functional changes in nerve roots and the dorsal root ganglia. In clinical situations, however, mechanical compression has also been considered an important factor in disc herniation. Methods. Eighteen dogs (9–15 kg) were used in this study. Four groups were used to assess the effect of each factor: 1) sham group (n = 3); 2) NP group (NP applied under the S1 lamina) (n = 5); 3) comp group (a plastic balloon placed under the S1 lamina) (n = 5); and 4) comp+NP group (a balloon and NP placed under the S1 lamina) (n = 5). Ascending cauda equina action potentials (CEAPs) and cauda equina–sensory nerve conduction velocity (SCV) were recorded before, immediately after, and 1 week after treatment. Histologic changes were also assessed by light microscopy. Results. There were no significant differences in CEAP and SCV among the four groups immediately after the treatment. However, 1 week after treatment, the amplitudes in the NP group, comp group, and comp+NP group were statistically significantly lower compared with those in the sham group. The comp+NP group showed significantly lower amplitude than did the NP group and comp group. Immediately after treatment, SCV in the NP group and comp group did not show significant differences compared with that in the sham group. However, 1 week after treatment, SCV in the comp+NP group was significantly lower compared with that in the sham group. Histologic changes such as intraneural edema, Schwann cell edema, and nerve fiber injury seemed to be more pronounced in the comp+NP group than in the other groups. Conclusions. It was shown that each of the assessed factors induces nerve dysfunction. However, the combination of mechanical compression (mass effect of herniated NP) and chemical irritation (inflammation around nerve root) may induce more nerve root injury than each factor per se.

Exogenous Tumor Necrosis Factor-α Induces Abnormal Discharges in Rat Dorsal Horn Neurons

STUDY DESIGN An electrophysiologic study to examine effects of exogenous application of tumor necrosis factor-alpha (TNF-alpha ) activities and nociresponses of dorsal horn neurons in the spinal cord at L5. OBJECTIVES To investigate the role of TNF-alpha in the induction and development of hyperalgesia in neural mechanisms responsible for a radicular pain. SUMMARY OF BACKGROUND DATA TNF-alpha is found in the herniated disc and known to play a pivotal role in the development of inflammatory hyperalgesia; however, it is not known whether TNF-alpha causes abnormal discharge in the dorsal horn neurons and enhances nociresponse. METHODS Single-unit activities of neurons in the L5 superficial dorsal horn were extracellularly recorded, using 28 urethane-anesthetized rats. The wide dynamic range and nociceptive-specific neurons activated by stimulation of the hind paw were selected. Effects of exogenous TNF-alpha were examined regarding 1) spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) responses of wide dynamic range neurons to noxious stimulation, and 3) morphologic changes in the dorsal root ganglion. RESULTS Application of TNF-alpha to the nerve root induced 1) a significant increase in spikes/sec in spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) enhanced responses of wide dynamic range neurons to noxious stimulation, and 3) inflammatory changes in the ganglion. CONCLUSION These results suggest the possibility that TNF-alpha produced in the vicinity of nerve roots due to disc herniation might cause ectopic discharges in primary afferent fibers and thereby induce the prolonged excitation in pain-processing neurons responsible for radicular pain.

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 &mgr;L of 1000 &mgr;g/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 &mgr;L 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 &mgr;m. 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 cmH2O in the NP+PS (control) group and 1.8 ± 0.4 cmH2O 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 cmH2O in the NP+PS group and 2.9 ± 0.8 cmH2O 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.

Nerve root infiltration and sympathetic block. An experimental study of intraradicular blood flow.

Study Design The nerve root of L7 was exposed, and a clamp was applied to simulate radiculopathy. In traradicular blood flow was measured at the takeoff point of the nerve root and at the distal to the dorsal root ganglion before and after nerve root infiltration with 2% lidocaina or physiological saline solution (control group),or sympathetic ganglion block with 2% lidocaine, Objectives To investigate one of the mechanisms of the therapeutic effect of nerve root infiltration by assessing changes in intraradicular blood flow. Summary of Background Data Increased intraradicular blood flow was noted both proximal and distal to the clamp after nerve root infiltration or sympathetic ganglion block with 2% lidocaine. No increase was seen after nerve root infiltration with saline solution,Macroscopic and microscopic examination showed that dye after nerve root infiltration did not spread beyond the clamped region to the proximal site. Methods Intraradicular blood flow was measured with a tissue blood flowmeter using the electrolytic hydrogen clearance method before and after nerve root infiltration with 2% lidocaine or physiologic saline solution (control group), or sympathetic ganglion block with 2% lidocaine. Results Increased intraradicular blood flow was noted both proximal and distal to the clamp after nerve root infiltration or sympathetic ganglion block with 2% lidocaine. No increase was seen after nerve root inflitration with saline solution. Conclusions An increase in intraradicular blood flow is related to one of the mechanisms of the therapeutic effect of nerve root infiltration. This effect may be mediated by the sympathetic nervous system.

A model for acute, chronic, and delayed graded compression of the dog cauda equina : presentation of the gross, microscopic, and vascular anatomy of the dog cauda equina and accuracy in pressure transmission of the compression model

Study Design A new model for controlled, graded compression of the dog cauda equina was developed using the dog lumbar spine. The model was defined regarding macroscopic, microscopic, and vascular anatomy and regarding accuracy in pressure transmission. Objectives The study was performed to develop a model for controlled, graded compression that would allow for acute, chronic, and delayed compression. Summary of Background Data There has been an increasing interest for the reactions of the spinal nerve roots to mechanical deformation. The previously used models have had limitations regarding the duration and the onset of the compression and possibilities for a controlled variation of the compression pressure on chronically compressed nerve roots. Methods Macroscopic examination, light microscopy, and ink injection of the vasculature was used to assess the anatomic characteristics of the nerve tissue and the vasculature of the cauda equina in the dog lower lumbar spine. The relation between known pressures in the compression balloon used to compress the cauda equina and the pressure in the central thecal sac was assessed by measuring the pressure in an artificial thecal sac with a pressure transducer. Results The neural and vascular anatomy was found to have a close resemblance to the human cauda equina. The pressure in the thecal sac was within 5% of the pressure in the compression balloon at various pressures between 0–200 mm Hg. Conclusions The presented model provides a good pressure transmission to the dog cauda equina, which has an anatomy that closely resembles the human cauda equina. The model may be well suited for physiologic studies of cauda equina compression. A double-balloon system may provide unique opportunities to induce chronic compression and delayed compression, i.e., additional compression after a certain time of chronic compression to resemble the changes in pressure that are characteristic for neurogenic claudication.