Effects of estradiol and progesterone on the sensitivity to pain and on morphine-induced antinociception in female rats.

Long-term ovariectomized (OVX) rats were exposed to 2- or 14-day replacement with pellets made of cholesterol (CHOL), estradiol (E2), progesterone (P4), or a combination of E2 and P4. Following the treatment with steroids the antinociceptive effect of morphine (5 mg/kg,sc) was measured by a hot-plate method. Pellets of E2 (0.5 and 5%) caused dose- and time-dependent reductions of morphine-induced antinociception as compared with OVX rats treated with CHOL pellets. Moreover, OVX rats pretreated with E2 pellets had decreased basic sensitivity to nociceptive stimulus (hyperalgesia). Treatment for 2 and 14 days with 75% P4 pellets produced significant reduction of MOR antinociception. The low dose of P4 (10% pellet) did not change the effect of MOR on Day 2 but significantly increased the antinociceptive effect of MOR on Day 14. Replacement of OVX rats with one 0.5% E2 pellet plus one 10% P4 pellet resulted in marked inhibition of the antinociceptive effect of MOR on Day 2 as well as on Day 14. Central injection 30 min before MOR of either LHRH antagonist or the antiserum against LHRH into OVX rats pretreated for 14 days with both steroids had no effect on the degree of the antinociception. The results suggest that the effects which ovarian steroids exert on opioid systems vary according to the dose, the duration of treatment, and the type of steroid administered.