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.
Caba
M
M
Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, Mexico.
González-Mariscal
G
G
Beyer
C
C
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D004597:Electroshock; D005260:Female; D007278:Injections, Spinal; D009118:Muscimol / Q000494:pharmacology*; D010052:Ovariectomy; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D011372:Progestins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects
D000700:Analgesics; D011372:Progestins; D018079:Receptors, GABA; D009118:Muscimol