Multiplicative interaction between narcotic agonisms expressed at spinal and supraspinal sites of antinociceptive action as revealed by concurrent intrathecal and intracerebroventricular injections of morphine.
Multiplicative interaction between narcotic agonisms expressed at spinal and supraspinal sites of antinociceptive action as revealed by concurrent intrathecal and intracerebroventricular injections of morphine.
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发表时间：
1980-12
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通讯作者：
J. C. Yeung;T. Rudy
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作者：
J. C. Yeung;T. Rudy
在第四脑室出口严重闭塞的大鼠中，将硫酸吗啡同时注射到脊髓蛛网膜下腔（0-10微克/4微升）和第三脑室（0-50微克/5微升）。选择鞘内 (i.t.) 和脑室内 (i.v.t.) 剂量的组合，以产生特定比例的脊髓上与脊髓 (SS:S) 激动作用。针对每个 SS:S 比率构建了甩尾和热板反应的剂量反应线，横坐标代表 i.v.t。吗啡剂量。据观察，静脉注射吗啡的镇痛效力明显增强。同时给予吗啡可显着增强该作用。静脉注射剂量反应线随着吗啡脊髓剂量的增加，吗啡逐渐向左移动。在脊髓和脊髓上剂量的最佳平衡 (SS:S = 1:1) 下，i.v.t. 的 ED50 值热板试验和甩尾试验的吗啡用量分别减少了 45 倍和 29 倍。注射吗啡的镇痛效果类似，但不那么深刻。同时静脉注射吗啡被观察到。数据的等值线分析表明，等值线是所有效应水平都具有极端负曲率的双曲线。对等值线的检查表明，在全身给予吗啡时可能获得的脊髓与脊髓上激动作用的所有比率下，脊髓-脊髓上相互作用是倍增的。结果表明，脊髓和脊髓上麻醉敏感部位的麻醉激动作用对于全身施用吗啡产生镇痛作用至关重要，并且这两个部位在逻辑上都不能被视为麻醉作用的“主要”部位。
In rats in which the fourth ventricular exits had been acutely occluded, morphine sulfate was injected concomitantly into the spinal subarachnoid space (0-10 micrograms/4 microliter) and into the third cerebral ventricle (0-50 micrograms/5 microliter). The combinations of intrathecal (i.t.) and intracerebroventricular (i.v.t.) dosages used were selected to yield particular ratios of supraspinal to spinal (SS:S) agonisms. Dose-response lines for both the tail-flick and hot plate responses were constructed for each SS:S ratio, with the abscissa representing i.v.t. morphine dosage. It was observed that the analgetic potency of morphine injected i.v.t. was profoundly potentiated by the concurrent administration of morphine i.t. Dose-response lines for i.v.t. morphine were shifted progressively to the left as the spinal dose of morphine was increased. At the optimal balance of spinal and supraspinal dosage (SS:S = 1:1), the ED50 values for i.v.t. morphine for the hot plate and tail-flick tests were reduced by factors of 45 and 29, respectively. A similar, but less profound, potentiation of the analgetic potency of morphine injected i.t. by concurrent administration of morphine i.v.t. was observed. Isobolographic analysis of the data revealed that the isobols were hyperbolas having extreme negative curvature of all effect levels. Inspection of the isobols indicated that, at all ratios of spinal to supraspinal agonism which could conceivably be obtained when morphine is given systemically, the spinal-supraspinal interaction is multiplicative. The results suggest that narcotic agonism at both spinal and supraspinal narcotic-sensitive sites is essential to the production of analgesia by systemically administered morphine and that neither site can logically be deemed the "primary" site of narcotic action.