Milne R J, Gamble G D, Holford N H
Department of Physiology, University of Auckland, New Zealand.
Brain Res. 1989 Jul 10;491(2):316-27. doi: 10.1016/0006-8993(89)90066-8.
Repeated exposure of a rat to a nociceptive testing environment ('habituation') enhances its sensitivity to noxious thermal stimuli20 and reduces the antinociceptive effect of a subsequent acute dose of morphine ('behavioural tolerance'). The present study quantitatively characterises the effects of habituation upon morphine antinociception using hot-plate (50 and 55 degrees C) and reflex withdrawal tests (dipping the tail and hindpaws into water at 49 degrees C). Dose-response relationships were modeled with the empirical function; E = Eo + (EMAX*DN)/(ED50N + DN) where E is the time-integrated response, EMAX is the response attributable to morphine, Eo is the baseline response, D is the dose and N is a steepness parameter. Habituation reduced EMAX in both hot-plate tests and also reduced Eo on the 50 degrees C hot-plate. In both reflex tests, habituation reduced Eo to that of spinal animals and EMAX to a value intermediate between that of intact and spinal animals. Neither the ED50 nor the value of N was altered by habituation. Acute spinal novice and habituated animals had similar dose-response curves and parameters. Sham spinalisation had no significant effect on any of the parameters. It is concluded that habituation to the nociceptive testing environment substantially reduces the bulbospinal contribution to morphine analgesia but has no effect upon the spinal component.
让大鼠反复暴露于伤害性测试环境（“习惯化”）会增强其对有害热刺激的敏感性20，并降低随后一剂急性吗啡的抗伤害作用（“行为耐受性”）。本研究使用热板（50和55摄氏度）和反射性退缩试验（将尾巴和后爪浸入49摄氏度的水中）定量表征习惯化对吗啡镇痛作用的影响。剂量-反应关系用经验函数建模：E = Eo + (EMAX*DN)/(ED50N + DN)，其中E是时间积分反应，EMAX是归因于吗啡的反应，Eo是基线反应，D是剂量，N是一个陡度参数。在两种热板试验中，习惯化均降低了EMAX，在50摄氏度热板试验中还降低了Eo。在两种反射试验中，习惯化都将Eo降低到脊髓动物的水平，将EMAX降低到完整动物和脊髓动物之间的中间值。习惯化既未改变ED50，也未改变N值。急性脊髓化的新手动物和习惯化动物具有相似的剂量-反应曲线和参数。假脊髓化对任何参数均无显著影响。得出的结论是，对伤害性测试环境的习惯化会大幅降低延髓脊髓对吗啡镇痛的贡献，但对脊髓成分没有影响。
