Nitric oxide regulation system in degenerative lumbar disease

Elevated nitric oxide (NO) production derived from NO synthase (NOS) activity has been shown in cerebrospinal fluid (CSF) in patients with degenerative lumbar disease (DLD). However, the regulatory mechanism of NO and the relationship of NO to clinical manifestations are unclear. In the present study, concentrations of NOx (nitrate NO3- and nitrite, NO2-), L-arginine (a substrate for NOS), and asymmetric dimethyl arginine (ADMA, an endogenous NOS inhibitor) in CSF were measured in two major DLDs: lumbar intervertebral disc herniation (LDH; 13 cases) and lumbar spinal canal stenosis (LSCS; 28 cases), and were compared with the levels in control patients with traumatic diseases. The levels of NO regulatory markers were also assessed according to Japanese Orthopedic Association (JOA) scores for the management of low back pain. NOx levels in LSCS patients (9.65 +/- 0.74 microM) were significantly higher than those in controls (5.26 +/- 0.27 microM) and in LDH patients (4.27 +/- 0.35 microM) (p < 0.01). ADMA levels were lower in LDH patients (0.016 +/- 0.008 pM) than in controls (0.045 +/- 0.011 pM) (p < 0.05), whereas those in LSCS patients (0.05 +/- 0.006 pM) were the same as in the controls. There was no significant difference in L-arginine levels among the groups. Nitrate or nitrite levels in these DLDs correlated with some of the JOA scores. The NO2- concentration was positively correlated with both JOA15 and JOA6 scores in LDH cases (p < 0.01). In LSCS cases, a positive correlation was found between NO2- concentration and JOA6 score, and between NO3- concentration and JOA9 (p < 0.01). In immunohistochemical analysis, inducible NOS and dimethylarginine dimethylaminohydrolase were expressed in mononuclear cells in tissues obtained from LSCS patients along with nitrotyrosine deposition, a footprint of NO radical formation. Our data suggested that the NO regulatory mechanism controlling the pathogenesis and progression of LDH might differ from that of LSCS.