Takahashi M, Izumi R, Kaneto H
Jpn J Pharmacol. 1984 Jun;35(2):175-9. doi: 10.1254/jjp.35.175.
Involvement of the catecholaminergic mechanism in foot shock (FS)- and immobilized-water immersion (IW)-stress-induced analgesia (SIA) and in the development of tolerance to the effect were investigated in mice. With daily treatment with clonidine or daily exposure to stresses, tolerance developed rapidly to the analgesic effect. Clonidine-induced analgesia, which could not be antagonized by naloxone, was potentiated in the animals rendered tolerant to FS-stress, and it was attenuated in the animals tolerant to IW-SIA. On the other hand, animals tolerant to clonidine failed to show the attenuation of FS- and IW-SIA. The analgesic effect of clonidine and the development of tolerance to the effect were not influenced by reserpine. However, reserpine pretreatment completely suppressed the analgesic effect induced by FS- and IW-stresses on the 1st day; but with daily exposure to the stress, the analgesic effect gradually appeared and returned to the control level on the 5th day. These results indicate not only the differences between clonidine analgesia and SIAs but also those between each SIA. Thus, the central catecholaminergic mechanisms play an important role in these SIAs and also in the development of tolerance to the effect, although the degree of participation of these mechanisms seems to be somewhat different between FS- and IW-SIA, as indicated by the cross-tolerance between clonidine analgesia and each SIA.
研究了小鼠中儿茶酚胺能机制在足部电击(FS)和固定-水浸(IW)应激诱导的镇痛(SIA)中的作用以及对该效应耐受性的发展。通过每日给予可乐定或每日暴露于应激,对镇痛效应的耐受性迅速发展。可乐定诱导的镇痛作用不能被纳洛酮拮抗,在对FS应激产生耐受性的动物中增强,而在对IW-SIA产生耐受性的动物中减弱。另一方面,对可乐定产生耐受性的动物并未表现出FS-和IW-SIA的减弱。可乐定的镇痛作用及其耐受性的发展不受利血平的影响。然而,利血平预处理在第1天完全抑制了FS和IW应激诱导的镇痛作用;但随着每日暴露于应激,镇痛作用逐渐出现并在第5天恢复到对照水平。这些结果不仅表明了可乐定镇痛与SIA之间的差异,也表明了各SIA之间的差异。因此,中枢儿茶酚胺能机制在这些SIA及其耐受性的发展中起重要作用,尽管这些机制的参与程度在FS-和IW-SIA之间似乎有所不同,如可乐定镇痛与各SIA之间的交叉耐受性所示。