Aloisi A M, Ceccarelli I
Institute of Human Physiology, University of Siena, Italy.
Neuroscience. 2000;95(2):559-66. doi: 10.1016/s0306-4522(99)00445-5.
The aim of this study was to assess the possible mediation of endogenous opioids in the effects of gonadal hormones on the responses to formalin pain. We studied the effects of intracerebroventricular injection of estradiol and/or naloxone on the magnitude and time-course of the formalin-evoked behavioural and hormonal responses of intact and gonadectomized male rats. Animals were gonadectomized or left intact; on days 20 and 21 after surgery, they were intracerebroventricularly injected with 17beta-estradiol (1 microg/5 microl) or saline. On day 22, the animals received naloxone (2.5 microg/5 microl) or saline intracerebroventricularly and then, 15 min later, were subcutaneously injected with formalin (50 microl, 5%) or only pricked with a syringe needle in the dorsal hindpaw. The rats were then introduced to a testing apparatus where the formalin-induced licking, flexing and jerking of the injected limb and the other spontaneous behaviours were recorded for 60 min. At the end of the test, the animals were killed and blood was collected from the trunk. Gonadectomy and naloxone increased flexing duration independently of the other treatments. In gonadectomized rats, estrogen increased licking duration and decreased paw-jerk frequency during the first phase (0-15 min) of the formalin test. During the second phase (16-60 min), licking was increased by estrogen only in intact animals. Treatment with naloxone completely abolished all these modifications. The three measures of activity (rearing, inner and outer crossing) showed that while in sham-treated animals the gonadectomy-induced decrease in activity was completely counteracted by estrogen administration, in formalin-treated animals the gonadectomy-induced decrease was not affected by estrogen. In fact, estrogen appeared to further depress the motor activities in the formalin groups. Naloxone reversed these modifications only for outer crossing frequency, blocking the gonadectomy-induced decrease in sham-treated animals. Corticosterone plasma levels were increased by formalin only in estrogen-treated animals, independently of naloxone. In conclusion, these data indicate an important role of both male gonadal hormones and estrogen in formalin-pain responses, acting through opiate and non-opiate mechanisms.
本研究的目的是评估内源性阿片类物质在性腺激素对福尔马林疼痛反应的影响中可能起到的介导作用。我们研究了脑室内注射雌二醇和/或纳洛酮对完整和去势雄性大鼠福尔马林诱发的行为和激素反应的幅度及时间进程的影响。将动物去势或保持完整；在手术后第20天和第21天，给它们脑室内注射17β - 雌二醇（1微克/5微升）或生理盐水。在第22天，给动物脑室内注射纳洛酮（2.5微克/5微升）或生理盐水，15分钟后，在其背部后爪皮下注射福尔马林（50微升，5%）或仅用注射器针头针刺。然后将大鼠放入测试装置中，记录福尔马林诱发的注射肢体的舔舐、弯曲和抽搐以及其他自发行为60分钟。测试结束时，处死动物并从躯干采集血液。去势和纳洛酮独立于其他处理增加了弯曲持续时间。在去势大鼠中，雌激素增加了福尔马林测试第一阶段（0 - 15分钟）的舔舐持续时间并降低了爪抽搐频率。在第二阶段（16 - 60分钟），仅在完整动物中雌激素增加了舔舐行为。用纳洛酮处理完全消除了所有这些改变。三种活动测量指标（站立、内外交叉）显示，在假处理动物中，去势引起的活动减少被雌激素给药完全抵消，而在福尔马林处理动物中，去势引起的活动减少不受雌激素影响。事实上，雌激素似乎进一步抑制了福尔马林组的运动活动。纳洛酮仅对外交叉频率逆转了这些改变，阻止了假处理动物中去势引起的减少。仅在雌激素处理的动物中，福尔马林使皮质酮血浆水平升高，与纳洛酮无关。总之，这些数据表明雄性性腺激素和雌激素在福尔马林疼痛反应中都起着重要作用，通过阿片类和非阿片类机制发挥作用。
