Sites of antinociceptive action of systemically injected morphine: involvement of supraspinal loci as revealed by intracerebroventricular injection of naloxone.
Sites of antinociceptive action of systemically injected morphine: involvement of supraspinal loci as revealed by intracerebroventricular injection of naloxone.
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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
在全身注射吗啡（10-150 mg/kg i. p.）和脑室内（i.v.t.）注射纳洛酮（3-20微克）。扩散研究表明，拮抗剂仍然局限于脊髓上的结构。在3到10微克的剂量之间。纳洛酮产生吗啡剂量-反应线的剂量依赖性的偏移，由10微克剂量产生的偏移足以消除高达75 mg/kg剂量的吗啡的镇痛作用。更高剂量的纳洛酮（例如，20微克）没有产生额外的Δ T变化，表明i.v.t.纳洛酮拮抗高全身剂量吗啡产生的镇痛。这些发现似乎表明，低至中等全身剂量吗啡产生的镇痛作用完全是由麻醉剂对脊髓上结构的作用介导的。然而，将纳洛酮注射到脊髓蛛网膜下腔的类似研究结果表明，全身给予低至中等剂量吗啡产生的镇痛作用仅通过对脊髓的作用介导。这个明显的悖论可以解决，如果一个假设，观察到的总镇痛后，低至中等剂量的吗啡全身是一个倍增的结果，而不是一个加法，在脊髓和脊髓上的行动网站，分别表示麻醉激动的相互作用。
Dose-response lines for the tail-flick and hot plate tests were obtained in rats which had received systemic injections of morphine (10-150 mg/kg i.p.) and intracerebroventricular (i.v.t.) injections of naloxone (3-20 micrograms). Diffusion studies indicated that the antagonist remained localized within supraspinal structures. Between the doses of 3 and 10 micrograms i.v.t. naloxone produced a dose-dependent rightward shifting of the morphine dose-response lines, the shift produced by the 10-micrograms dose being sufficient to abolish the analgetic action of morphine doses as large as 75 mg/kg. Higher doses of naloxone (e.g., 20 micrograms) produced no additional rightward shift, indicating an inability of i.v.t. naloxone to antagonize the analgesia produced by high systemic doses of morphine. These findings seem to suggest that analgesia produced by low to moderate systemic doses of morphine is mediated entirely by an action of the narcotic upon supraspinal structures. However, the results of an analogous study in which naloxone was injected into the spinal subarachnoid space indicated that analgesia produced by morphine given systemically in low to moderate doses is mediated exclusively by an action on the spinal cord. This apparent paradox can be resolved if one assumes that the total analgesia observed after a low to moderate systemic dose of morphine is a result of a multiplicative, rather than an additive, interaction of narcotic agonisms expressed at the spinal and supraspinal sites of action, respectively.