Increase in formalin-induced tonic pain by 5alpha-reductase and aromatase inhibition in female rats.

Little is known about the role of steroidogenic enzymes in pain modulation. This study examined the effects of 5α-reductase and aromatase inhibition on formalin-induced tonic pain (FITP) in adult female rats. The animals received subcutaneous injection (5 mg/kg) of finasteride (an inhibitor of 5α-reductase) and letrozole (an inhibitor of aromatase), either separately or in combination, 15 min before formalin injection at a low (0.25%) and high (2.5%) concentration. Pretreatment with inhibitors increased FITP evoked by injection of 0.25% formalin, but they were not effective on 2.5% formalin pain. The enhancing effects of finasteride and letrozole on FITP induced by 2.5% formalin was demonstrated by inhibitory actions of these drugs on morphine (7 and 10 mg/kg, intraperitoneal) induced antinociception. The nervous system could be considered as the main target of the enzymes inhibition, since the pronociceptive effect was also observed after administration of inhibitors to ovariectomized rats. Altogether, these findings suggest that the biological activity of the enzymes 5α-reductase and aromatase modulates FITP and may help to develop effective therapeutic strategies to counteract pain.