Increased antinociception by alpha-adrenoceptor drugs after spinal cord noradrenaline depletion.
Increased antinociception by alpha-adrenoceptor drugs after spinal cord noradrenaline depletion.
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脊髓去甲肾上腺素耗竭后，α-肾上腺素受体药物可增加抗伤害作用。
DOI：
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发表时间：
1987
影响因子：
5
通讯作者：
E. Sundström
中科院分区：
文献类型：
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作者：
C. Post;M. Persson;T. Archer;B. Minor;W. Danysz;E. Sundström
据报道，耗尽球脊髓NA纤维束的动物对鞘内注射去甲肾上腺素(NA)的抗伤害性作用高度敏感。在本研究中，我们测定了全身或鞘内注射去甲肾上腺素后的抗伤害性作用。使用去甲肾上腺素和选择性α2-肾上腺素能受体激动剂异丙肾上腺素和可乐定。用6-羟基多巴胺(6-OHDA)或成年动物鞘内注射6-OHDA或全身注射N-2-氯乙基-N-乙基-2-溴苄胺(DSP4)来耗竭NA。这些神经毒素被发现导致严重的脊髓NA枯竭，而不影响多巴胺(DA)或5-羟色胺(5-HT)的水平。鞘内注射NA、可乐定和胍法辛的抗伤害性作用在耗竭大鼠比对照组更强。研究还发现，系统给药的可乐定和胍法辛对耗竭的动物比对照动物有更强的作用。总而言之，NA下行通路的耗竭导致对鞘内给药NA和选择性α2-肾上腺素能受体激动剂可乐定和愈创新的功能性超敏。研究还发现，全身给药可乐定和胍法辛对NA耗竭的动物比对照动物有更强的作用。
Animals depleted of the bulbospinal NA fiber tracts have been reported to be supersensitive to antinociceptive effects of intrathecally administered noradrenaline (NA) in vivo. In the present investigation, the antinociceptive effects were determined after systemic or intrathecal injections of noradrenergic agents. NA and the selective alpha 2-adrenoceptor agonists guanfacine and clonidine were used. NA depletion was performed by treatment neonatally with 6-hydroxydopamine (6-OHDA), or in adult animals by intrathecal 6-OHDA administration or systemic N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4). The neurotoxins were found to cause a severe depletion of spinal NA without affecting dopamine (DA) or 5-hydroxytryptamine (5-HT) levels. The antinociceptive effects of intrathecal injection of NA, clonidine and guanfacine were more strongly enhanced in the depleted than in the control rats. It was also found that clonidine and guanfacine given systemically had a stronger effect in depleted than in control animals. In conclusion, depletion of descending NA pathways induces functional supersensitivity both to intrathecally administered NA and to the selective alpha 2-adrenoceptor agonists clonidine and guanfacine. It was also found that systemically administered clonidine and guanfacine had a stronger effect in NA-depleted than in control animals.