The effects of estradiol and progesterone on pain sensitivity and brain opioid receptors in ovariectomized rats

Abstract

Previous studies in our laboratory have shown that estradiol and progesterone affect beta-endorphin and Met-enkephalin levels in specific brain regions and that these effects are diurnally controlled. The present investigation was conducted to evaluate the effects of estradiol and progesterone on pain latency and brain opioid receptors of ovariectomized rats. Female Sprague-Dawley rats (100-120 g) adapted to a 12 hr light:12 hr dark illumination cycle were used in these studies. Animals were ovariectomized under pentobarbital anesthesia. After a recovery period of 10-14 days, estradiol (50 micrograms/kg/day in 0.2 ml olive oil) and progesterone (5 mg/kg/day in 0.1 ml olive oil) were administrated subcutaneously in the dorsal neck region alone and in combination at 16:00 hr for 7 days. Control animals received 0.2 ml olive oil. Control and treated groups were evaluated daily for pain latency postinjection using the tailflick and hotplate methods. On Day 7 of drug treatment, animals were sacrificed by decapitiation after pain latency evaluations. Whole brains were removed and immediately frozen at -70 degrees C. Binding and affinity of brain opiate receptors were determined for each treatment group. Results obtained indicate that estradiol and progesterone treatment alone or in combination significantly alter pain latency. This alteration in pain was not accompanied by any change in affinity or number of mu opioid receptors. However, an increase in Kd of kappa opiate receptors was observed following treatment with estradiol, progesterone, or their combination. This increase in Kd of kappa opiate receptors may in part explain the increased hotplate sensitivity following estrogen administration. The present findings suggest that the decrease in pain sensitivity induced by estradiol or progesterone could not be explained by their effects on opioid receptors. The previously reported effects of estradiol and progesterone on brain levels of beta-endorphin and Met-enkephalin may contribute to the analgesic effects of these steroids.