Spinal nerve lesion induces upregulation of neuronal nitric oxide synthase in the spinal cord. An immunohistochemical investigation in the rat.
The possibility nitric oxide (NO) is involved the neurodegenrative mechanisms 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 contralateral side. In these rats, ultrastructural investigations showed distorted neurons, membrane disruption and myelin vesiculation. Sham operated rats did not show either NOS upregulation or structural changes in the spinal cord. Pretreatment with L-NAME significantly reduced NOS upregulation and the structural changes in the spinal cord were less pronounced. These observations strongly indicate a putative role of NOS in the pathophysiology of chronic nerve lesion. Our results may provide a new strategy to treat chronic neuropathic pain or to minimise neurodegeneration in the patients suffering from such diseases of the nervous system.
Gordh
T
T
Department of Anaesthesiology, University Hospital, Uppsala, Sweden.
Sharma
H S
HS
Alm
P
P
Westman
J
J
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000201:enzymology*; D013127:Spinal Nerves / Q000473:pathology*; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester