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 t o be caused by mechanical compression and related to the presence of nucleu s pulposus in the epidural space. Autologous nucleus pulposus has been show n to induce endoneural edema and to decrease nerve-conduction velocity in s pinal nerve roots in experimental disc herniation models, and inflammatory mediators have been suggested to be involved in these mechanisms. Nitric ox ide, a potent inflammatory mediator, is implicated in vasoregulation, neuro transmission, and neuropathic pain. Nitric oxide synthesis can be induced b y different cytokines, e.g,, tumor necrosis factor-alpha, which recently wa s shown to be of pathophysiological importance in experimental disc herniat ion. The enzyme nitric oxide synthase mediates the production of nitric oxi de. Three series of experiments were performed in rat and pig disc herniati on models to (a) investigate nitric oxide synthase activity in spinal nerve roots after exposure to autologous nucleus pulposus and (b) evaluate the e ffects of systemic treatment with aminoguanidine, a nitric oxide synthase i nhibitor, on vascular permeability and nerve-conduction velocity. In a disc herniation model in the rat, calcium-independent nitric oxide synthase act ivity was measured in nerve roots exposed to nucleus pulposus; however, no nitric oxide synthase activity was detected in nerve roots from animals tha t underwent a sham operation, reflecting increased inducible nitric oxide s ynthase activity. In nucleus pulposus-exposed spinal nerve roots in the pig , the edema was less severe after systemic aminoguanidine administration th an without aminoguanidine treatment. Aminoguanidine treatment also signific antly reduced the negative effect of nucleus pulposus on nerve-conduction v elocity in spinal nerve roots in the pig. These results demonstrate that nu cleus pulposus increases inducible nitric oxide synthase activity in spinal nerve roots and that nitric oxide synthase inhibition reduces nucleus pulp osus-induced edema and prevents reduction of nerve-conduction velocity. Fur thermore, the results suggest that nitric oxide is involved in the pathophy siological effects of nucleus pulposus in disc herniation.