Bornschein R L, Crockett R S, Smith R P
Pharmacol Biochem Behav. 1977 Jun;6(6):621-6. doi: 10.1016/0091-3057(77)90085-5.
Response to thermal stimulation and the analgesic effectiveness of morphine during various phases of the diurnal cycle were assessed by the hotplate method. Saline treated controls exhibited shortest reaction times during the last quarter of the light-phase and first quarter of the dark phase. Longest reaction times were recorded during the last quarter of the dark phase. Doses of 4, 8, 16, and 32 mg/kg of morphine was administered IP at the peak and trough of the pain sensitivity rhythm. The ED50 (95% C.L.) during the last quarter of the light phase was found to be 14.60 (10.6-20.0) mg/kg while during the last quarter of the dark phase the ED50 was found to be 5.85 (4.5-7.7) mg/kg. In a second experiment, independent groups of ten mice each were injected SC with 8 mg/kg of morphine at three hr intervals over a 48 hr test session. Peak analgesic activity was obtained in the group injected during the last quarter of the dark phase while minimal analgesic effectiveness was obtained during the third quarter of the light phase. Central administration of morphine via the intraventricular route yielded the same relationship, i.e., maximal analgesic effectiveness during the last quarter of the dark phase.
采用热板法评估了昼夜周期各阶段对热刺激的反应以及吗啡的镇痛效果。生理盐水处理的对照组在光照期的最后四分之一和黑暗期的第一季度反应时间最短。最长反应时间记录在黑暗期的最后四分之一。在疼痛敏感性节律的峰值和谷值时，腹腔注射4、8、16和32mg/kg剂量的吗啡。在光照期的最后四分之一期间，ED50（95%置信区间）为14.60（10.6 - 20.0）mg/kg，而在黑暗期的最后四分之一期间，ED50为5.85（4.5 - 7.7）mg/kg。在第二个实验中，每组十只小鼠的独立组在48小时的测试期间每隔三小时皮下注射8mg/kg的吗啡。在黑暗期的最后四分之一注射的组中获得了最大镇痛活性，而在光照期的第三季度获得了最小的镇痛效果。通过脑室内途径中枢给予吗啡产生了相同的关系，即在黑暗期的最后四分之一期间具有最大的镇痛效果。
