Roerig S C, Fujimoto J M, Tseng L F
Research Service, Veterans Administration Medical Center, Milwaukee, Wisconsin.
J Pharmacol Exp Ther. 1988 Dec;247(3):1107-13.
Morphine administered concurrently by i.c.v. plus intrathecal (i.t.) injection produces a multiplicative (synergistic) interaction for antinociception in the tail-flick test. Inasmuch as i.c.v. administered beta-endorphin has been proposed to produce antinociception by activating a descending pain inhibitory system different from that activated by morphine, the present experiments compared the two systems in mice. The responses to i.c.v., i.t. and combinations of i.c.v. plus i.t. administration of morphine and beta-endorphin were evaluated by determination of ED50 values which were plotted as isobolograms and compared to calculated theoretical additive ED50 values. The following combinations gave additive interactions: i.c.v. plus i.t. beta-endorphin, i.c.v. beta-endorphin plus i.t. morphine and i.t. morphine plus i.t. beta-endorphin. These results were consistent with the hypothesis that i.c.v. beta-endorphin stimulates supraspinal epsilon receptors which activate a descending pathway involving enkephalinergic neuronal mediation and spinal postsynaptic mu receptors. Stimulation of these mu receptors by i.t. morphine or i.t. beta-endorphin together with the supraspinal effect of beta-endorphin resulted in an additive interaction. Multiplicative interactions were obtained for the following combinations: i.c.v. morphine plus i.t. morphine, i.c.v. morphine plus i.t. beta-endorphin and i.c.v. morphine plus i.c.v. beta-endorphin. Morphine administered i.c.v. stimulated supraspinal mu receptors to activate a descending pain inhibitory pathway which is mediated spinally by monoamines. The i.t. agonists in this case activated the spinal mu receptor which is presumed to be part of the beta-endorphin descending pathway described above. Thus, when both pathways were activated simultaneously the interaction was multiplicative.(ABSTRACT TRUNCATED AT 250 WORDS)
通过脑室内（i.c.v.）加鞘内（i.t.）注射同时给予吗啡，在甩尾试验中产生抗伤害感受的倍增（协同）相互作用。鉴于已提出脑室内给予β-内啡肽通过激活与吗啡激活的不同的下行性疼痛抑制系统来产生抗伤害感受，本实验在小鼠中比较了这两种系统。通过测定ED50值来评估对脑室内、鞘内以及脑室内加鞘内给予吗啡和β-内啡肽的反应，将这些值绘制成等效应线图，并与计算出的理论相加ED50值进行比较。以下组合产生相加相互作用：脑室内加鞘内β-内啡肽、脑室内β-内啡肽加鞘内吗啡以及鞘内吗啡加鞘内β-内啡肽。这些结果与以下假设一致，即脑室内β-内啡肽刺激脊髓上的ε受体，该受体激活涉及脑啡肽能神经元介导的下行通路和脊髓后突触μ受体。鞘内吗啡或鞘内β-内啡肽对这些μ受体的刺激以及β-内啡肽的脊髓上效应导致相加相互作用。以下组合获得倍增相互作用：脑室内吗啡加鞘内吗啡、脑室内吗啡加鞘内β-内啡肽以及脑室内吗啡加脑室内β-内啡肽。脑室内给予吗啡刺激脊髓上的μ受体以激活下行性疼痛抑制通路，该通路在脊髓由单胺介导。在这种情况下，鞘内激动剂激活脊髓μ受体，该受体被认为是上述β-内啡肽下行通路的一部分。因此，当两条通路同时被激活时，相互作用是倍增性的。（摘要截短于250字）
