SPINAL NERVE LESION INDUCES UP-REGULATION OF NEURONAL NITRIC-OXIDE SYNTHASE IN THE SPINAL-CORD - AN IMMUNOHISTOCHEMICAL INVESTIGATION IN THE RAT

The possibility nitric oxide (NO) is involved the neurodegenrative mec hanisms in the spinal cord following a chronic peripheral nerve lesion was examined using NOS immunohistochemistry. Spinal nerve lesion at L -5 and L-6 level was produced according to the Chung model, a model of neuropathic pain and rats were allowed to survive for 8 weeks. In one group of animals L-NAME was given intraperitoneally (1-2 mg/kg, i.p. daily) for 6 weeks. Sham operated rats, in which the spinal nerve was exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of NOS which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the cont ralateral side. In these rats, ultrastructural investigations showed d istorted neurons, membrane disruption and myelin vesiculation. Sham op erated rats did not show either NOS upregulation or structural changes in the spinal cord. Pretreatment with L-NAME significantly reduced NO S upregulation and the structural changes in the spinal cord were less pronounced. These observations strongly indicate a putative role of N OS in the pathophysiology of chronic nerve lesion. Our results may pro vide a new strategy to treat chronic neuropathic pain or to minimise n eurodegeneration in the patients suffering from such diseases of the n ervous system.