Kamei J, Ohhashi Y, Aoki T, Kawasima N, Kasuya Y
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Brain Res. 1992 Feb 7;571(2):199-203. doi: 10.1016/0006-8993(92)90655-s.
To investigate the possible mechanisms of the alterations in morphine-induced analgesia observed in diabetic mice, we examined the influence of streptozotocin-induced (STZ-induced) diabetes on analgesia mediated by the different opioid receptors. The antinociceptive potency of morphine (10 mg/kg), administered s.c., as determined by both the tail-pinch and the tail-flick test, was significantly reduced in diabetic mice as compared to that in controls. Mice with STZ-induced diabetes had significantly decreased sensitivity to intracerebroventricularly (i.c.v.) administered mu-opioid agonists, such as morphine (10 micrograms) and [D-Ala2,N-Me Phe4,Gly-ol5]enkephalin (DAMGO, 0.5 micrograms). However, i.c.v. administration of [D-Pen2,5]enkephalin (DPDPE, 5 micrograms), a delta-opioid agonist, and U-50,488H (50 micrograms), a kappa-opioid agonist, produced pronounced antinociception in both control and diabetic mice. Furthermore, there were no significant differences in antinociceptive potency between diabetic and control mice when morphine (1 microgram), DAMGO (10 micrograms), DPDPE (0.5 micrograms) or U-50,488H (50 micrograms) was administered intrathecally. In conclusion, mice with STZ-induced diabetes are selectively hyporesponsive to supraspinal mu-opioid receptor-mediated antinociception, but they are normally responsive to activation of delta- and kappa-opioid receptors.
为了研究糖尿病小鼠中观察到的吗啡诱导镇痛改变的可能机制,我们检测了链脲佐菌素诱导(STZ诱导)的糖尿病对不同阿片受体介导的镇痛的影响。通过夹尾试验和甩尾试验测定,皮下注射10mg/kg吗啡时,糖尿病小鼠的抗伤害感受效能与对照组相比显著降低。STZ诱导糖尿病的小鼠对脑室内(i.c.v.)注射的μ-阿片激动剂,如吗啡(10μg)和[D-Ala2,N-Me Phe4,Gly-ol5]脑啡肽(DAMGO,0.5μg)的敏感性显著降低。然而,脑室内注射δ-阿片激动剂[D-Pen2,5]脑啡肽(DPDPE,5μg)和κ-阿片激动剂U-50,488H(50μg)在对照小鼠和糖尿病小鼠中均产生明显的抗伤害感受作用。此外,鞘内注射吗啡(1μg)、DAMGO(10μg)、DPDPE(0.5μg)或U-50,488H(50μg)时,糖尿病小鼠和对照小鼠之间的抗伤害感受效能没有显著差异。总之,STZ诱导糖尿病的小鼠对脊髓上μ-阿片受体介导的抗伤害感受选择性低反应,但它们对δ-和κ-阿片受体的激活通常有反应。