Takahashi M, Senda T, Tokuyama S, Kaneto H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Jpn J Pharmacol. 1990 Aug;53(4):487-94. doi: 10.1254/jjp.53.487.
The analgesic effect induced by exposure to psychological stress, using a communication box (psychological stress-induced analgesia, PSY-SIA), was completely antagonized by 10 min pretreatment with 0.5, 1 and 2 mg/kg of nor-binaltorphimine and with 0.5 and 1 mg/kg of Mr2266, selective kappa-opioid receptor antagonists, in the tail pinch method. Neither footshock (FS)- nor forced swimming (SW)-SIA was affected by these antagonists. The selective delta-opioid receptor antagonist naltrindole, at doses up to 20 mg/kg, had no appreciable effect on PSY-SIA. Daily morphine treatment, 10 mg/kg, s.c., resulted in tolerance to the analgesic effect, and concurrent exposure to PSY-stress suppressed the development of morphine tolerance. The substitution of treatment with U-50,488H for PSY-stress still resulted in analgesia on the initial day; and likewise, the suppression by U-50,488H of the development of morphine tolerance was replicated by PSY-stress. Pretreatment with nor-binaltorphimine antagonized the suppressive effect of PSY-stress on the development of morphine tolerance without affecting the analgesic effect of morphine per se. These results provide further evidence that PSY-SIA involves the mediation by kappa-opioid receptor mechanisms.
采用交流箱（心理应激诱导镇痛，PSY - SIA）诱导的心理应激镇痛效应，在夹尾法中，经0.5、1和2mg/kg的去甲纳曲酮和0.5及1mg/kg的Mr2266（选择性κ-阿片受体拮抗剂）预处理10分钟后完全被拮抗。足部电击（FS）或强迫游泳（SW）诱导的SIA均不受这些拮抗剂影响。高达20mg/kg剂量的选择性δ-阿片受体拮抗剂纳曲吲哚对PSY - SIA没有明显影响。每日皮下注射10mg/kg吗啡会导致对镇痛效应产生耐受性，同时暴露于心理应激可抑制吗啡耐受性的发展。用U - 50,488H替代心理应激处理在最初几天仍会产生镇痛作用；同样，心理应激也能复制U - 50,488H对吗啡耐受性发展的抑制作用。去甲纳曲酮预处理可拮抗心理应激对吗啡耐受性发展的抑制作用，而不影响吗啡本身的镇痛效果。这些结果进一步证明PSY - SIA涉及κ-阿片受体机制的介导。
