Iwasaki H, Collins J G, Saito Y, Uchida H, Kerman-Hinds A
Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Anesth Analg. 1991 Mar;72(3):325-9. doi: 10.1213/00000539-199103000-00008.
This is one of a series of experiments designed to examine the possible pharmacologic basis for analgesia normally associated with pregnancy. The antinociceptive effects of low-dose (0.1 mg/kg) subcutaneous clonidine on analgesia associated with pregnancy were evaluated in rats. Colorectal distention thresholds and tail-flick latencies were determined in timed pregnant rats (n = 27) before mating, on days 7 and 21 of gestation, and on postpartum day 7. Immediately after baseline testing on each of those days, animals received 0.1 mg/kg clonidine subcutaneously and were retested 30 min later. On day 21 of gestation, 20 micrograms/kg naloxone (n = 9) and 0.2 mg/kg yohimbine (n = 5) were intravenously administered after clonidine testing, and animals were retested 15 min later. In the absence of clonidine, pregnant animals demonstrated a statistically significant increase in their tolerance of colorectal distention pressures and longer latencies to tail-flick withdrawal on day 21 of gestation. Clonidine produced a further significant increase in distention thresholds on day 21 of gestation but did not change these thresholds on any other day, nor did it change tail-flick latencies. Naloxone and yohimbine reversed the effect of clonidine on the distention thresholds on day 21. Systemic clonidine, at a dose lower than that required to produce antinociception in nonpregnant rats, enhanced pregnancy-induced analgesia to visceral stimulation late in pregnancy, an effect that was reversed by naloxone and yohimbine. These results suggest a synergistic antinociceptive effect of clonidine due to an interaction with an endogenous opiate system that is only activated late in pregnancy.
这是一系列实验中的一个，旨在研究与妊娠相关的镇痛可能的药理学基础。在大鼠中评估了低剂量（0.1毫克/千克）皮下注射可乐定对妊娠相关镇痛的抗伤害感受作用。在定时妊娠大鼠（n = 27）交配前、妊娠第7天和第21天以及产后第7天测定结肠扩张阈值和甩尾潜伏期。在这些日子中的每一天进行基线测试后，动物立即皮下注射0.1毫克/千克可乐定，并在30分钟后重新测试。在妊娠第21天，可乐定测试后静脉注射20微克/千克纳洛酮（n = 9）和0.2毫克/千克育亨宾（n = 5），并在15分钟后重新测试动物。在没有可乐定的情况下，妊娠动物在妊娠第21天对结肠扩张压力的耐受性有统计学显著增加，甩尾撤回潜伏期延长。可乐定在妊娠第21天使扩张阈值进一步显著增加，但在任何其他日子均未改变这些阈值，也未改变甩尾潜伏期。纳洛酮和育亨宾在妊娠第21天逆转了可乐定对扩张阈值的作用。全身给予可乐定，其剂量低于在未妊娠大鼠中产生抗伤害感受所需的剂量，增强了妊娠后期对内脏刺激的妊娠诱导镇痛，这种作用被纳洛酮和育亨宾逆转。这些结果表明，由于与仅在妊娠后期才被激活的内源性阿片系统相互作用，可乐定具有协同抗伤害感受作用。
