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Pharmacology and physiology of pregnancy induced analgesia

妊娠镇痛的药理学和生理学

基本信息

批准号：
13671559
负责人：
IWASAKI Hiroshi
金额：
$ 1.41万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671559/
关键词：
pregnancy endogenous analgesia formalin test

项目摘要

Pregnancy-induced analgesia is of interest to anesthesiologists because of the observation that parturients may require less anesthetic or analgesic drugs. This is one of series of experiments to examine the pharmacology of pregnancy-induced analgesia in rats.In pregnant animals, a significant increase in tail-flick latency(TFL) was demonstrated on day 21 of gestation. Intrathecally administered ketamine (50 and 100 microg) produced a dose dependent prolongation of TFL on day 21 of gestation. However, this potentiative effect in TFL after ketamine injection were not observed on days 7 and 17 of gestation, and post-partum day 7 (Fig 1). A similar pattern of augmentation in AUC after ketamine was observed on day 21 of gestation. The main finding of this study was that intrathecally administered ketamine potentiated the degree of pregnant-induced analgesia to thermal noxious stimulation late in pregnancy. These results suggest a synergistic antinociceptive effect of ketamine due to an interaction with an endogenous opiate system that is only activated late in pregnancy. (Journal of Anesthesia 13:74:1999, Anesthesiology 91:A778:1999).Then we investigated, in rats, the effects of pregnancy on pain behaviorous induced by electrical stimulation of the peripheral fields, or by subcutaneous injection of formalin into the hind paw. This study demonstrated that pregnancy can increase cutaneous pain thresholds to electrical as well as chemical stimuli (Anesthesiology 2001;95:A748).Endomorphine-1 is a novel endogenous u-opioid ligand. The potent antinociceptive effect of endomorphine-1 microinjected into the ventrolateral periaqueductal gray is mediated through the u-opioid receptor and is potentiated by concomitant administration of L-type calcium channel blocker, nifedipine (Anesth Analg 2003;96:1065-71)

妊娠镇痛是麻醉学家感兴趣的，因为观察到产妇可能需要较少的麻醉或镇痛药物。这是一系列研究大鼠妊娠镇痛药理学的实验之一。在妊娠动物中，在妊娠第21天证明了甩尾潜伏期（TFL）的显著增加。鞘内注射氯胺酮（50和100 μ g）在妊娠第21天产生剂量依赖性TFL延长。然而，在妊娠第7天和第17天以及产后第7天未观察到氯胺酮注射后TFL的这种增强效应（图1）。在妊娠第21天观察到氯胺酮给药后AUC增加的相似模式。本研究的主要发现是，鞘内注射氯胺酮增强了妊娠晚期对热伤害性刺激的妊娠诱导镇痛程度。这些结果表明，由于与内源性阿片系统的相互作用，氯胺酮的协同抗伤害性作用，这是只在妊娠后期激活。（Journal of Anesthesia 13：74：1999，Anesthesiology 91：A778：1999）。然后，我们在大鼠中研究了妊娠对通过外周场的电刺激或通过将福尔马林皮下注射到后爪中诱导的疼痛行为的影响。这项研究表明，怀孕可以增加皮肤对电刺激以及化学刺激的疼痛阈值（Anesthesiology 2001;95：A748）。微量注射到中脑导水管周围灰质腹外侧的内吗啡-1的有效抗伤害感受作用通过u-阿片受体介导，并且通过伴随施用L-型钙通道阻断剂硝苯地平而增强（Anesth Analg 2003;96：1065-71）。