Singh Preet, Kongara Kavitha, Harding David, Ward Neil, Dukkipati Venkata Sayoji Rao, Johnson Craig, Chambers Paul
Massey University, Institute of Veterinary, Animal and Biomedical Sciences, Palmerston North, New Zealand.
Massey University, Institute of Fundamental Sciences, Palmerston North, New Zealand.
BMC Neurol. 2018 Apr 19;18(1):43. doi: 10.1186/s12883-018-1047-y.
The objective of this study was to compare the changes in the electroencephalogram (EEG) in response to noxious stimuli with tail flick and hot plate responses of rats administered opiorphin.
Female Sprague -Dawley rats (n = 8 per group) randomly received intravenous (IV) injection of morphine (1 mg/kg,) or opiorphin (2 mg/kg,) or saline (0.5 ml,) in each of the three testing methods (EEG, tail flick and hot plate). Each type of test (n = 24 per test) was conducted in different population of rats on separate occasions. The tail flick and hot plate latencies were recorded until 5 min after test drug administration to conscious rats. The EEG was recorded in anaesthetised rats subjected to noxious thermal and electrical stimuli after test drug administration. At the end of 5 min in each of the testing methods rats were administered naloxone subcutaneously (SC) (1 mg/kg) and the test procedure was repeated.
There was no significant increase in the median frequency and spectral edge frequency (F50 & F95) of EEG, indicators of nociception, of morphine and opiorphin groups after noxious stimulation. Noxious stimuli caused a significant increase in both F50 and F95 of the saline group. An injection of naloxone significantly increased the F50, thus blocking the action of both opiorphin and morphine. There was a significant increase in the tail flick latency after administration of opiorphin and morphine as compared to the baseline values. Rats of morphine group spent significantly longer on the hot plate when compared to those of the opiorphin and saline groups. There was no significant difference in the hot plate latencies of opiorphin and saline groups.
The results of this study suggest that the analgesic effect of opiorphin occurs at the spinal level and it is not as effective as morphine at supraspinal level. It may be due to rapid degradation of opiorphin or limited ability of opiorphin to cross the blood brain barrier or a higher dose of opiorphin is required for its action in the brain. Pharmacokinetic/pharmacodynamics studies along with in vivo penetration of opiorphin in the cerebrospinal fluid are required for further evaluation of opiorphin analgesia.
本研究的目的是比较给予阿片啡肽的大鼠在接受伤害性刺激时脑电图（EEG）的变化与甩尾和热板反应。
雌性斯普拉格 - 道利大鼠（每组n = 8只）在三种测试方法（EEG、甩尾和热板）中，每种方法都随机接受静脉注射吗啡（1毫克/千克）、阿片啡肽（2毫克/千克）或生理盐水（0.5毫升）。每种类型的测试（每次测试n = 24只）在不同的大鼠群体中分别进行。记录清醒大鼠给予测试药物后5分钟内的甩尾和热板潜伏期。在给予测试药物后，对麻醉大鼠施加伤害性热刺激和电刺激时记录EEG。在每种测试方法的5分钟结束时，给大鼠皮下注射纳洛酮（1毫克/千克），并重复测试程序。
伤害性刺激后，吗啡组和阿片啡肽组EEG的中值频率和频谱边缘频率（F50和F95）（伤害感受指标）无显著增加。伤害性刺激使生理盐水组的F50和F95均显著增加。注射纳洛酮显著增加了F50，从而阻断了阿片啡肽和吗啡的作用。与基线值相比，给予阿片啡肽和吗啡后甩尾潜伏期显著增加。与阿片啡肽组和生理盐水组相比，吗啡组大鼠在热板上停留的时间显著更长。阿片啡肽组和生理盐水组的热板潜伏期无显著差异。
本研究结果表明，阿片啡肽的镇痛作用发生在脊髓水平，在脊髓上水平不如吗啡有效。这可能是由于阿片啡肽快速降解、阿片啡肽穿过血脑屏障的能力有限或其在脑中发挥作用需要更高剂量的阿片啡肽。需要进行药代动力学/药效学研究以及阿片啡肽在脑脊液中的体内渗透研究，以进一步评估阿片啡肽的镇痛作用。
