期刊
NEUROSCIENCE
卷 101, 期 1, 页码 189-196出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0306-4522(00)00328-6
关键词
intrathecal; metabolism; neurotransmitter; pain
资金
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R29GM035523, R01GM035523, R23GM035523] Funding Source: NIH RePORTER
- NIGMS NIH HHS [GM35523] Funding Source: Medline
Spinally released norepinephrine is thought to produce analgesia in part by stimulating alpha (2)-adrenergic receptors, which in turn leads to nitric oxide synthesis. Also, nitric oxide is known to react with norepinephrine in vivo in the brain to form 6-nitro-norepinephrine, which inhibits neuronal norepinephrine reuptake. In the present study, we tested the hypothesis that formation of 6-nitro-norepinephrine occurs in the spinal cord and that intrathecal administration of 6-nitro-norepinephrine produces analgesia by stimulating norepinephrine release. 6-Nitro-norepinephrine was present in rat spinal cord tissue and microdialysates of the dorsal horn and intrathecal space. Intrathecal norepinephrine injection increased 6-nitro-norepinephrine. 6-Nitro-norepinephrine also stimulated norepinephrine release in dorsal spinal cord in vitro. Intrathecal injection of 6-nitro-norepinephrine produced antinociception and interacted additively with norepinephrine for antinociception. Spinal noradrenergic nerve destruction increased antinociception from intrathecally injected norepinephrine, but decreased antinociception from 6-nitro-norepinephrine. These results suggest a functional interaction between spinal nitric oxide and norepinephrine in analgesia, mediated in part by formation of 6-nitro-norepinephrine. Stimulation of auto-inhibitory alpha (2)-adrenergic receptors at noradrenergic synapses decreases norepinephrine release. Paradoxically, a2-adrenergic agonist injection increases and al-adrenergic antagonist injection decreases norepinephrine release in the spinal cord. 6-Nitro-norepinephrine may be an important regulator of spinal norepinephrine release and could explain the positive feedback on norepinephrine release after activation of spinal alpha (2)-adrenergic receptors. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.
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