<span style="font-size: 21.5pt;mso-bidi-font-size:14.5pt;font-family:"Times New Roman","serif"">Antinociceptive activity of a neurosteroid tetrahydrodeoxycorticosterone (5α-pregnan-3α-21-diol-20-one) and its possible mechanism(s) of action </span>

Abstract

<span style="font-size: 15.5pt;mso-bidi-font-size:8.5pt;font-family:" times="" new="" roman","serif""="">The present study investigates the effects of a neurosteroid tetrahydrodeoxycorticosterone (5α-pregnan-3α-21-diol-20- one) in two experimental models of pain sensitivity in mice. &nbsp;Tetrahydrodeoxycorticosterone (2.5, 5 mg/kg, ip) dose dependently decreased the licking response in formalin test and increased the tail flick latency (TFL) in tail flick test. Bicuculline (2 mg/kg, ip), 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, ip), 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.

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