Jayaram A, Singh P, Carp H M
Oregon Health Sciences University, Department of Anesthesiology, Portland, 97201-3098, USA.
Anesthesiology. 1995 May;82(5):1283-7. doi: 10.1097/00000542-199505000-00024.
Stress-induced analgesia is a well recognized phenomenon in animals and humans in which endogenous opioids have been implicated. However, analgesia induced by surgical stress has not been reported. The purpose of this study was to determine whether surgery evokes analgesia and to examine the effect of SCH 32615, an inhibitor of one of the enzymes (enkephalinase) responsible for the degradation of enkephalins, on this analgesia, in mice.
Analgesia was tested using the hot-plate test. Animals were tested before any procedure was done and then at hourly intervals thereafter. Under halothane anesthesia, the anterior abdominal wall was incised, and the abdominal aorta was compressed against the vertebral column for 1 s. This was repeated for a total of three times at 5-s intervals. At the end of the procedure, the following drug(s) were administered subcutaneously to different groups of animals: (1) no drugs, only surgery (n = 15); (2) 5 mg/kg naloxone (n = 15); (3) 150 mg/kg SCH 32615 (n = 14); (4) 150 mg/kg SCH 32615 plus 5 mg/kg naloxone (n = 15); and (5) SCH 32615 vehicle (0.9% methylcellulose; n = 13). Two more groups of animals were included as controls and were anesthetized, but no surgical procedure was performed. One control group (n = 13) received 0.9% methylcellulose and the other 150 mg/kg SCH 32615 (n = 12).
Hot-plate latency was significantly longer after surgery (hot-plate latency at 4 h after surgery 29.3 +/- 3.2 (SE) s and at 5 h 30.7 +/- 5 s versus baseline 15.8 +/- 7 s; P < 0.05). Naloxone (5 mg/kg) inhibited this analgesic effect of surgery. SCH 32615 significantly enhanced this analgesia (percentage of maximal possible effect (%MPE) at 4 h 33.7 +/- 8.7%, at 5 h 27.5 +/- 4.7%, and at 6 h 23.2 +/- 4.7%; P < 0.05 compared to all other groups), and naloxone antagonized its effect. Anesthesia without surgery did not evoke subsequent analgesia, and SCH 32615 was not analgesic in the absence of antecedent surgery.
Surgery activated endogenous analgesia, the development of which was prevented by naloxone. SCH 32615, an enkephalinase inhibitor, significantly enhanced this analgesia.
应激诱导的镇痛是动物和人类中一种广为人知的现象，其中内源性阿片类物质被认为与之相关。然而，手术应激诱导的镇痛尚未见报道。本研究的目的是确定手术是否能诱发镇痛，并研究SCH 32615（一种负责脑啡肽降解的酶（脑啡肽酶）的抑制剂）对小鼠这种镇痛作用的影响。
采用热板法测试镇痛效果。在进行任何操作之前对动物进行测试，之后每隔一小时测试一次。在氟烷麻醉下，切开前腹壁，将腹主动脉压在脊柱上1秒。以5秒的间隔重复此操作，共进行三次。在操作结束时，对不同组的动物皮下注射以下药物：（1）不注射药物，仅进行手术（n = 15）；（2）5 mg/kg纳洛酮（n = 15）；（3）150 mg/kg SCH 32615（n = 14）；（4）150 mg/kg SCH 32615加5 mg/kg纳洛酮（n = 15）；（5）SCH 32615的赋形剂（0.9%甲基纤维素；n = 13）。另外两组动物作为对照，进行麻醉但不进行手术操作。一组对照组（n = 13）接受0.9%甲基纤维素，另一组接受150 mg/kg SCH 32615（n = 12）。
手术后热板潜伏期显著延长（术后4小时热板潜伏期为29.3±3.2（标准误）秒，5小时为30.7±5秒，而基线为15.8±7秒；P < 0.05）。纳洛酮（5 mg/kg）抑制了手术的这种镇痛作用。SCH 32615显著增强了这种镇痛效果（4小时时最大可能效应百分比（%MPE）为33.7±8.7%，5小时为27.5±4.7%，6小时为23.2±4.7%；与所有其他组相比P < 0.05），且纳洛酮拮抗了其作用。未进行手术的麻醉未诱发后续镇痛，且在没有先前手术的情况下SCH 32615无镇痛作用。
手术激活了内源性镇痛，纳洛酮可阻止其产生。脑啡肽酶抑制剂SCH 32615显著增强了这种镇痛作用。
