Post C, Persson M L, Archer T, Minor B G, Danysz W, Sundström E
Eur J Pharmacol. 1987 May 7;137(1):107-16. doi: 10.1016/0014-2999(87)90188-9.
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.
据报道，延髓脊髓去甲肾上腺素（NA）纤维束缺失的动物在体内对鞘内注射去甲肾上腺素（NA）的抗伤害感受作用超敏感。在本研究中，在全身或鞘内注射去甲肾上腺素能药物后测定其抗伤害感受作用。使用了NA以及选择性α2-肾上腺素能受体激动剂胍法辛和可乐定。通过在新生期用6-羟基多巴胺（6-OHDA）处理来实现NA耗竭，或在成年动物中通过鞘内注射6-OHDA或全身给予N-2-氯乙基-N-乙基-2-溴苄胺盐酸盐（DSP4）来实现。发现这些神经毒素会导致脊髓NA严重耗竭，而不影响多巴胺（DA）或5-羟色胺（5-HT）水平。与对照大鼠相比，鞘内注射NA、可乐定和胍法辛在NA耗竭的大鼠中产生的抗伤害感受作用增强得更明显。还发现，全身给予可乐定和胍法辛在NA耗竭的动物中比在对照动物中产生的作用更强。总之，下行NA通路的耗竭会诱导对鞘内注射NA以及选择性α2-肾上腺素能受体激动剂可乐定和胍法辛产生功能性超敏感。还发现，全身给予可乐定和胍法辛在NA耗竭的动物中比在对照动物中产生的作用更强。
