Craft Rebecca M, Ulibarri Catherine, Leitl Michael D, Sumner Jean E
Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA.
Eur J Pain. 2008 May;12(4):472-9. doi: 10.1016/j.ejpain.2007.07.014. Epub 2007 Sep 14.
To clarify the activational role of ovarian hormones on pain and analgesia, the present study determined whether estradiol (E2) modulation of nociception and morphine antinociception in adult female rats depends on (1) the dose of E2 and (2) the interval between E2 treatment and nociceptive testing. Female rats were ovariectomized (OvX) and either oil vehicle (0), or E2 (0.25, 2.5 or 25 microg/0.1 ml vehicle) was injected s.c. two consecutive days of every four days for five cycles before testing. Either 4, 24, 48 or 96 h after the last injection, nociception was evaluated on the 50 degrees C hotplate and warm water tail withdrawal tests before and after escalating doses of s.c. morphine. Lordosis behavior and uterine weight were assessed in other rats at the same E2 doses and time points. E2 significantly lengthened latency to respond on the hotplate test at 24 h after the last injection, but had no significant effect on tail withdrawal latencies. The lower doses of E2 significantly increased morphine antinociceptive potency at 4-24 h on one or both tests, but the intermediate E2 dose significantly decreased morphine potency at 48 h on the hotplate test. Thus, E2 modulation of morphine antinociception in the adult female rat is bidirectional, and occurs at E2 doses producing cyclic changes in sexual behavior, uterine weight and vaginal cytology that are similar to those observed in gonadally intact, cycling females.
为阐明卵巢激素在疼痛和镇痛方面的激活作用，本研究确定成年雌性大鼠中雌二醇（E2）对伤害感受和吗啡镇痛作用的调节是否取决于：（1）E2的剂量；（2）E2处理与伤害性测试之间的间隔时间。将雌性大鼠进行卵巢切除（OvX），在测试前每四天连续两天皮下注射油剂载体（0）或E2（0.25、2.5或25微克/0.1毫升载体），共进行五个周期。在最后一次注射后4、24、48或96小时，在50摄氏度热板上评估伤害感受，并在皮下注射递增剂量的吗啡前后进行温水甩尾试验。在相同的E2剂量和时间点，对其他大鼠评估脊柱前凸行为和子宫重量。在最后一次注射后24小时，E2显著延长了热板试验中的反应潜伏期，但对甩尾潜伏期没有显著影响。较低剂量的E2在4 - 24小时的一项或两项测试中显著提高了吗啡的镇痛效力，但中等剂量的E2在48小时的热板试验中显著降低了吗啡的效力。因此，成年雌性大鼠中E2对吗啡镇痛作用的调节是双向的，且发生在能引起性行为、子宫重量和阴道细胞学出现周期性变化的E2剂量下，这些变化与性腺完整、处于发情周期的雌性大鼠中观察到的相似。
