Antinociceptive activity of a neurosteroid tetrahydrodeoxycorticosterone (5alpha-pregnan-3alpha-21-diol-20-one) and its possible mechanism(s) of action.
The present study investigates the effects of a neurosteroid tetrahydrodeoxycorticosterone (5alpha-pregnan-3alpha-21-diol-20-one) in two experimental models of pain sensitivity in mice. Tetrahydrodeoxycorticosterone (2.5, 5 mg/kg, i.p.) dose dependently decreased the licking response in formalin test and increased the tail flick latency (TFL) in tail flick test. Bicuculline (2 mg/kg, i.p.), a GABA(A) receptor antagonist blocked the antinociceptive effect of tetrahydrodeoxycorticosterone in TFL test but failed to modulate licking response in formalin test. Naloxone (1 mg/kg, i.p.), an opioid antagonist effectively attenuated the analgesic effect of tetrahydrodeoxycorticosterone in both the models. Tetrahydrodeoxycorticosterone pretreatment potentiated the antinociceptive response of morphine, an opioid compound and nimodipine, a calcium channel blocker in formalin as well as TFL test. Thus, tetrahydrodeoxycorticosterone exerts an analgesic effect, which may be mediated by modulating GABA-ergic and/or opioid-ergic mechanisms and voltage-gated calcium channels.
Mediratta
P K
PK
Department of Pharmacology, University College of Medical Sciences and GTB Hospital, Delhi, India.
Gambhir
M
M
Sharma
K K
KK
Ray
M
M
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D008297:Male; D051379:Mice
D000700:Analgesics; D058787:GABA-A Receptor Antagonists; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone