Spinal norepinephrine release from nitric oxide species is not increased following peripheral nerve injury in rats.
Alpha(2)-Adrenergic agonists increase the synthesis of nitric oxide (NO) in the spinal cord in both in vitro slice perfusion and in vivo microdialysis. In the normal condition, inhibition of NO synthase (NOS) has little effect on antinociception from alpha(2)-adrenergic agonists. However, following peripheral nerve injury, NOS inhibitors completely block the antihypersensitivity effects of alpha(2)-adrenergic agonists. It is possible that this increased reliance on NO may reflect a positive feedback release of norepinephrine (NE) stimulated by NO conjugates. For example, both S-nitroso-l-cysteine (SNC) and 6-NO(2)-norepinephrine (6-NO(2)-NE) release NE in rat spinal synaptosomes in a concentration-dependent manner and both are formed in spinal cord in vivo. In the current study, we tested whether SNC and 6-NO(2)-NE induced spinal NE release is increased in animals with peripheral nerve injury compared to normals. Crude spinal cord synaptosomes were prepared from nerve ligated and normal rats, loaded with [(3)H]NE and incubated with SNC or 6-NO(2)-NE. In a separate experiment, spinal cords from both groups were sonicated and the amount of NE measured using HPLC. NE release stimulated by SNC or 6-NO(2)-NE in lumbar dorsal spinal cord tissue did not differ between normal and nerve ligated groups. This suggests that increased spinal NE release from locally produced SNC or 6-NO(2)-NE is not the mechanism underlying the reliance of alpha(2)-adrenergic agonists on NO following peripheral nerve injury. Increased NE content and trend towards greater NE uptake in nerve injured spinal cord are consistent with increased noradrenergic innervation density of the spinal cord following peripheral nerve injury.
Zhu
Xiaoying
X
Program of Neuroscience and Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Li
Xinhui
X
Eisenach
James C
JC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D059348:Peripheral Nerve Injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols / Q000494:pharmacology*; D013116:Spinal Cord / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D003545:Cysteine; D009638:Norepinephrine