Miaskowski Christine, Sutters Kimberly A, Taiwo Yetunde O, Levine Jon D
School of Nursing, University of California at San Francisco, San Francisco, CA 94143 USA School of Medicine, University of California at San Francisco, San Francisco, CA 94143 USA School of Dentistry, University of California at San Francisco, San Francisco, CA 94143 USA.
Pain. 1992 Apr;49(1):137-144. doi: 10.1016/0304-3959(92)90200-U.
Interactions between selective opioid agonists acting at spinal mu-, delta-, and kappa-opioid receptors were evaluated by co-administering a low-antinociceptive dose of the selective delta-agonist, DPDPE, or the selective kappa-agonist, U50,488H, with sequentially increasing doses of the selective mu-agonist, DAMGO, intrathecally. Antinociceptive synergy (i.e., a more than additive antinociceptive effect) was observed with both combinations of opioid agonists tested. The demonstration of antinociceptive synergy suggests that the subtypes of spinal opioid receptors can act, at least in part, through a common neural circuit. Since our measure of antinociception, the Randall-Selitto paw-withdrawal test, is dependent on a normally functioning motor system, we also evaluated the effects of these same combinations of opioid peptides on motor coordination using a rotarod treadmill. A low-antinociceptive dose of DPDPE or U50,488H co-administered intrathecally, with sequentially increasing doses of DAMGO, did not worsen the decrement in rotarod performance observed with the same doses of DAMGO administered as a single agent. In fact, the low-antinociceptive dose of DPDPE significantly attenuated the decrease in rotarod performance produced when the same dose of DAMGO was administered as a single agent. The results of this study suggest that intrathecal combinations of selective mu- with both delta- or kappa-selective opioid agonists can produce antinociceptive synergy without producing an increase in motor side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
通过鞘内联合给予低抗伤害感受剂量的选择性δ-激动剂DPDPE或选择性κ-激动剂U50,488H与逐渐增加剂量的选择性μ-激动剂DAMGO，评估作用于脊髓μ-、δ-和κ-阿片受体的选择性阿片激动剂之间的相互作用。在所测试的两种阿片激动剂组合中均观察到抗伤害感受协同作用（即超过相加的抗伤害感受效应）。抗伤害感受协同作用的证明表明脊髓阿片受体亚型至少部分可通过共同的神经回路发挥作用。由于我们评估抗伤害感受的方法，即Randall-Selitto爪退缩试验，依赖于正常运作的运动系统，我们还使用转棒式跑步机评估了这些相同阿片肽组合对运动协调性的影响。鞘内联合给予低抗伤害感受剂量的DPDPE或U50,488H与逐渐增加剂量的DAMGO，并未使与单独给予相同剂量DAMGO时观察到的转棒性能下降情况恶化。事实上，低抗伤害感受剂量的DPDPE显著减轻了单独给予相同剂量DAMGO时所产生的转棒性能下降。本研究结果表明，选择性μ-与δ-或κ-选择性阿片激动剂的鞘内组合可产生抗伤害感受协同作用，而不会增加运动副作用。（摘要截短至250字）
