Perispinal progestins enhance the antinociceptive effects of muscimol in the rat

The intrathecal (IT) injection of progesterone (PROG) or three of its ring A-reduced metabolites (5 beta,3 alpha-pregnanolone, 5 alpha,3 alpha-pregnanolone, or 5 beta,3 beta-pregnanolone) did not significantly alter any of two pain thresholds (vocalization threshold to tail shock, VTTS, or tail flick latency, TFL) in ovariectomized rats when tested in a wide range of doses (2.5-250 micrograms). When combined with a subanalgesic dose of muscimol (MUSC; 1 microgram IT), PROG and its two 3 alpha-hydroxy derivatives, but not the 3 beta, caused significant analgesia in the VTTS but not in the TFL test. No clear dose-response relationships were noted in the analgesic response to the combination of the progestins and MUSC. The present results indicate that PROG, either directly or through its ring A-reduction, can modulate nociceptive information by enhancing the action of GABA agonists on GABAA receptors.