No abstract

Autologous nucleus pulposus is known to have injurious effects on spinal nerve roots when applied epidurally. Both inflammatory and immunological mechanisms have been implicated in this regard. Various proinflammatory substances might be released or activated by nucleus pulposus and might affect the endoneural nerve root vessels. The present study assessed nucleus pulposus-induced early vascular reactions and the possibility of blocking these reactions with intravenous, high-dose, methylprednisolone pretreatment. In 25 pigs, the S2 and S3 nerve roots were exposed. In five pigs (control group), retroperitoneal fat was applied epidurally on the nerve roots, and the other 20 pigs had nucleus pulposus applied. This group was sub-divided into the treatment group (n = 8), in which the pigs were pretreated with intravenous high-dose methylprednisolone (30 mg/kg body weight), and the nontreatment group (n = 12), in which the pigs received a corresponding volume of saline solution. After 2 hours, Evans blue labeled albumin was injected intravenously 5 minutes before death. Endoneural extravasation of Evans blue labeled albumin was evaluated with fluorescence microscopy. A marked albumin leakage was found in 67% of the nontreated animals, in 25% of those in the treatment group, and in none of the control animals. These results demonstrate that nucleus pulposus can induce a rapid increase in endoneural vascular permeability in spinal nerve roots after epidural application. This increase can be partially prevented by pretreatment with high-dose methylprednisolone.

Limited data are available about the long-term outcome of surgical treatment for lumbar spinal stenosis, and there is a wide variation in reported success rates. There is also a controversy regarding differences in long-term outcome between patients undergoing decompressive surgery alone and those undergoing both decompression and fusion. The aim of this study was to evaluate the long-term clinical outcome and possible complications of decompressive surgery, with special reference to possible differences between patients undergoing fusion, with or without instrumentation, and those undergoing decompression alone. All 124 patients undergoing first-time surgery for lumbar spinal stenosis between 1982 and 1991 at our department were included, and their medical records were reviewed retrospectively. Ninety-six of the patients were available for follow-up and were re-examined by an independent investigator and assessed with a questionnaire after a mean follow-up period of 7.1 (range 4.0-12.2) years. Sixty-five percent of all the patients at the follow-up were subjectively satisfied. Eighty-eight percent of the patients reported constant or daily leg pain preoperatively compared to 43% at follow-up. Constant or daily low back pain was reported by 83% of the patients preoperatively compared to 45% at follow-up. Improvement in walking capacity was found in most patients, and only 4% of the patients who had a preoperatively documented maximum walking distance reported a decreased walking capacity. Twenty-four (25%) of all patients used analgesics daily at the time of follow-up, 34 patients (35%) occasionally and 38 patients (40%) never. The patients with fusions, instrumented or non-instrumented, did not differ significantly from the unfused patients regarding any of the above-mentioned parameters. The results of the study showed that most patients demonstrated a considerable improvement in walking capacity at follow-up. This improvement was significant (P < 0.001) and of clinical importance. A significant improvement regarding both low back pain and leg pain was found postoperatively compared to preoperatively (P < 0.001). There were no statistical differences, judged by all the evaluated parameters, regarding the clinical outcome between patients who were fused and those who were not. Neither were any significant differences found between instrumented fusions compared to uninstrumented fusions. In accordance with most other long-term follow-up studies, about two-thirds (65%) of the patients claimed a satisfactory result at follow-up.

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.