Evaluation of the analgesic effect of neurosteroids and their possible mechanism of action.

The present study investigates the effect of progesterone (P), a pregnane precursor of neurosteroids and 4-chlordiazepam (4-CD), a high affinity ligand for mitochondrial diazepam binding inhibitor receptor (MDR) that stimulates neurosteroid synthesis, in both acute, (tail flick latency test, TFL) and chronic, (formalin-induced pain response, FT), models. Both P and 4-CD showed an analgesic response in these models. The effect of P and 4-CD was antagonized by bicuculline on TEL but not in FT. However, naloxone attenuated the antinociceptive response of P and 4-CD in TFL as well as FT. Further, P and 4-CD pretreatment potentiated the analgesic effect of morphine and nimodipine in both the models of pain sensitivity. Thus, neurosteroids produce an antinociceptive effect which may be mediated by modulation of GABAergic and/or opiodergic mechanisms as well as voltage gated calcium channels.