Modulation by estrogen and progesterone of the effect of muscimol on nociception in the spinal cord

Abstract

The GABA A agonist, muscimol, administered intrathecally (IT) to the spinal cord at a dose (1 μg) that was subthreshold for affecting pain thresholds (vocalization-threshold-to-tail-shock: VTTS, and tail-flick latency: TFL) in overiectomized, hormonally untreated rats, showed a significant increase in VTTS up to 30 min postinjection in intact females only in proestrus or estrus. The treatment produced no significant effect on TFL at any stage of the estrous cycle. IT muscimol produced a significant increase in VTTS (but not TFL) in ovariectomized rats primed with estradiol benzoate (EB) for 2 days and tested 40 hr after the second injection but had no effect in females primed with a single EB injection and tested 15 min later. By contrast, ovariectomized females primed with progesterone (P) for 15 min exhibited a significant increase in pain thresholds after IT muscimol in both the VTTS and TFL tests. When EB-primed females (2 days) received P 4 hr prior to muscimol there was no analgesia produced by IT muscimol, in contrast to EB-primed females receiving P 15 min prior to IT muscimol in which there was significant analgesia. These results suggest a mechanism for antagonistic effects for estrogen and progesterone.