Plesan A, Hoffmann O, Xu X J, Wiesenfeld-Hallin Z
Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Neurosci Lett. 1999 Mar 19;263(1):53-6. doi: 10.1016/s0304-3940(99)00109-3.
The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan on morphine-induced antinociception was studied with the hot plate test in Sprague-Dawley (SD), Wistar-Kyoto (WK), Spontaneously Hypertensive (SHR) and Dark-Agouti (DA) rats. Subcutaneous morphine at 5 mg/kg induced significant antinociception in all four rats strains. Subcutaneous dextromethorphan at 15 and 45 mg/kg, but not 5 mg/kg, significantly and dose-dependently potentiated morphine-induced antinociception in SDs, WKs and SHRs, but not in DAs. In SHRs and DAs the antinociceptive effect of morphine was followed by prolonged hyperalgesia, which was reduced (SHRs) or abolished (DAs) by dextromethorphan. These results suggest that there are significant differences among rat strains in their response to morphine and in the ability of dextromethorphan to potentiate morphine-induced antinociception. These differences are possibly of genetic origin. Moreover, these data show that morphine, at least in some strains of rats, induced a delayed and NMDA receptor-dependent hyperalgesic response, supporting the notion that administration of opiates may activate NMDA receptors, leading to reduced antinociceptive effect and the development of hyperalgesia.
采用热板试验，在斯普拉格-道利（SD）大鼠、威斯塔-京都（WK）大鼠、自发性高血压（SHR）大鼠和黑褐相间（DA）大鼠中研究了非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂右美沙芬对吗啡诱导的镇痛作用的影响。皮下注射5mg/kg吗啡可在所有这四种品系大鼠中诱导出显著的镇痛作用。皮下注射15mg/kg和45mg/kg而非5mg/kg的右美沙芬，可显著且呈剂量依赖性地增强SD大鼠、WK大鼠和SHR大鼠中吗啡诱导的镇痛作用，但对DA大鼠无此作用。在SHR大鼠和DA大鼠中，吗啡的镇痛作用之后会出现长时间的痛觉过敏，右美沙芬可减轻（SHR大鼠）或消除（DA大鼠）这种痛觉过敏。这些结果表明，大鼠品系之间在对吗啡的反应以及右美沙芬增强吗啡诱导的镇痛作用的能力方面存在显著差异。这些差异可能源于遗传。此外，这些数据表明，吗啡至少在某些品系大鼠中会诱导出一种延迟的、NMDA受体依赖性的痛觉过敏反应，这支持了阿片类药物的给药可能激活NMDA受体，从而导致镇痛作用减弱和痛觉过敏发生的观点。
