Pharmacology and physiology of pregnancy induced analgesia

麻醉医生对妊娠镇痛很感兴趣，因为观察到产妇可能需要较少的麻醉剂或止痛药。这是研究大鼠妊娠镇痛药理学的一系列实验之一。在怀孕动物中，在怀孕第21天，甩尾潜伏期(TFL)显著增加。鞘内注射氯胺酮(50和100微克)可剂量依赖性地延长妊娠第21天的TFL。然而，在注射氯胺酮后的TFL中，在妊娠7天和17天以及产后7天没有观察到这种增强作用(图1)。在妊娠第21天观察到氯胺酮后AUC增大的相似模式。本研究的主要发现是鞘内给药氯胺酮增强了妊娠晚期对热伤害性刺激的镇痛程度。这些结果表明，氯胺酮具有协同的抗伤害性作用，这是由于它与内源性阿片系统相互作用，而内源性阿片系统只在怀孕后期激活。(麻醉学杂志13：74：1999，麻醉学91：A778：1999)。然后，我们在大鼠身上研究了怀孕对外周视野电刺激或后爪皮下注射福尔马林引起的疼痛行为的影响。这项研究表明，怀孕可以提高皮肤对电刺激和化学刺激的痛阈值(麻醉学2001；95：A748)。内吗啡-1是一种新的内源性U-阿片配体。内吗啡-1微量注射到中脑导水管周围灰质腹外侧区的强大的抗伤害性作用是通过u-阿片受体介导的，并同时给予L类钙通道阻滞剂硝苯地平(Anesth alig2003；96：1065-71)。

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)