Intravenous opioids stimulate norepinephrine and acetylcholine release in spinal cord dorsal horn - Systematic studies in sheep and an observation in a human
Intravenous opioids stimulate norepinephrine and acetylcholine release in spinal cord dorsal horn - Systematic studies in sheep and an observation in a human
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DOI：
10.1097/00000542-199601000-00017
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发表时间：
1996-01-01
期刊：
影响因子：
8.8
通讯作者：
Eisenach, JC
中科院分区：
文献类型：
--
作者：
Bouaziz, H;Tong, CY;Eisenach, JC
背景：阿片类药物通过直接作用和激活神经通路释放非阿片类递质而产生镇痛作用。本研究测试了全身应用阿片类药物是否激活了脊髓去甲肾上腺素和胆碱能下行通路。方法：检测静脉注射吗啡对20只绵羊脑脊液和背角微透析液中去甲肾上腺素和乙酰胆碱浓度的影响。结果：静脉注射吗啡(0、0.5、1 mg/kg)后，脑脊液中去甲肾上腺素和乙酰胆碱含量呈剂量依赖性增加，而肾上腺素和多巴胺含量无明显变化。静脉注射纳洛酮和鞘内注射咪唑生均可阻断吗啡的作用。在微透析实验中，静脉注射吗啡增加了背角中去甲肾上腺素和乙酰胆碱的浓度，但不增加肾上腺素或多巴胺的浓度。相比之下，静脉注射吗啡对腹角的这些单胺类物质中的任何一种都没有影响。静脉注射纳洛酮和切断颈髓均可阻断吗啡对去甲肾上腺素的作用。结论：这些结果支持阿片类药物全身应用通过纳洛酮敏感机制引起脊髓去甲肾上腺素和乙酰胆碱释放的功能研究。Idazoxan阻断吗啡对脑脊液去甲肾上腺素的影响是意想不到的，这表明去甲肾上腺素和乙酰胆碱在脊髓中的释放可能都受到α(2)肾上腺素受体的调节。微透析实验表明，脑脊液中去甲肾上腺素和乙酰胆碱水平的增加是静脉注射吗啡引起的球脊髓通路激活所致。
Background: Opioids produce analgesia by direct effects as well as by activating neural pathways that release nonopioid transmitters. This study tested whether systematically administered opioids activate descending spinal noradrenergic and cholinergic pathways.Methods: The effect of intravenous morphine on cerebrospinal fluid and dorsal horn microdialysate concentrations of norepinephrine and acetylcholine was examined in 20 sheep. Animals received either intravenous morphine or fentanyl alone, or morphine plus intravenous naloxone or intrathecal idazoxan.Results: Intravenous morphine (0, 0.5, 1 mg/kg, intravenous) produced dose-dependent increases in cerebrospinal fluid norepinephrine and acetylcholine, but not epinephrine or dopamine. Morphine's effect was blocked by intravenous naloxone and by intrathecal idazoxan. In microdialysis experiments, intravenous morphine increased the concentration of norepinephrine and acetylcholine, but not epinephrine or dopamine, in the dorsal horn. In contrast, intravenous morphine exerted no effect on any of these monoamines in the ventral horn. Intravenous naloxone and cervical cord transection each blocked morphine's effect on dorsal horn norepinephrine.Conclusions: These results support functional studies that indicate that systematically administered opioids cause spinal norepinephrine and acetylcholine release by a naloxone-sensitive mechanism. Idazoxan blockade of morphine's effects on cerebrospinal fluid norepinephrine was unexpected, and suggests that both norepinephrine and acetylcholine release in the spinal cord may be regulated by alpha(2)-adrenoceptors. Microdialysis experiments suggest increased norepinephrine and acetylcholine levels in cerebrospinal fluid resulted from intravenous morphine-induced activation of bulbospinal pathways.