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鞘内注射孤啡肽对炎症或外周神经切断后大鼠屈肌反射的影响。

Effects of intrathecal orphanin FQ on a flexor reflex in the rat after inflammation or peripheral nerve section.

作者信息

Xu I S, Grass S, Wiesenfeld-Hallin Z, Xu X J

机构信息

Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.

出版信息

Eur J Pharmacol. 1999 Apr 1;370(1):17-22. doi: 10.1016/s0014-2999(99)00111-9.

Abstract

We examined the effects of intrathecal orphanin FQ, the endogenous ligand for the orphan opioid-like receptor, on the hamstring nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats after carrageenan-induced inflammation or unilateral sciatic nerve transection. As described previously [Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996. Orphanin FQ or antiorphanin FQ: potent spinal antinociceptive effect of orphanin FQ/orphanin FQ in the rat. NeuroReport 7, 2092-2094.], intrathecal orphanin FQ induced a dose-dependent depression of the flexor reflex with a ED50 of 965 ng. Initial reflex facilitation was noted in some experiments at lower doses (10 or 100 ng). A similar bi-phasic response pattern to intrathecal orphanin FQ was observed in experiments conducted in inflamed or axotomized rats. However, the magnitude of the initial reflex facilitation was significantly increased in inflamed rats compared to normals whereas the duration of reflex depression was significantly shortened. The ED50 for reflex depression was 2.4 jig for inflamed rats. In contrast, axotomy did not significantly alter the facilitatory and depressive effect of orphanin FQ with ED50 for reflex depression being 374 ng. These results confirmed an inhibitory action of orphanin FQ on spinal nociception in rats. It is suggested that the effect of orphanin FQ may be modulated by inflammation and nerve injury. In particular, unlike morphine, there seems to be no reduction in the effect of spinal orphanin FQ in inducing antinociception after peripheral nerve axotomy.

摘要

我们研究了孤啡肽FQ(一种孤儿阿片样受体的内源性配体)对卡拉胶诱导炎症或单侧坐骨神经横断后去大脑、脊髓横断、未麻醉大鼠腘绳肌伤害性屈肌反射的影响。如先前所述[Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996.孤啡肽FQ或抗孤啡肽FQ:孤啡肽FQ/孤啡肽FQ在大鼠中的强效脊髓镇痛作用。《神经报告》7, 2092 - 2094.],鞘内注射孤啡肽FQ可引起屈肌反射的剂量依赖性抑制,半数有效剂量(ED50)为965 ng。在一些实验中,较低剂量(10或100 ng)时可观察到初始反射易化。在炎症或轴突切断的大鼠中进行的实验中,观察到对鞘内注射孤啡肽FQ有类似的双相反应模式。然而,与正常大鼠相比,炎症大鼠中初始反射易化的程度显著增加,而反射抑制的持续时间显著缩短。炎症大鼠中反射抑制的ED50为2.4 μg。相比之下,轴突切断并未显著改变孤啡肽FQ的易化和抑制作用,反射抑制的ED50为374 ng。这些结果证实了孤啡肽FQ对大鼠脊髓伤害感受的抑制作用。提示孤啡肽FQ的作用可能受炎症和神经损伤的调节。特别是,与吗啡不同,外周神经轴突切断后,脊髓孤啡肽FQ诱导镇痛的作用似乎没有降低。

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