The increasing use of opioids in the treatment of pain and their prolonged time of use asks to enlarge the knowledge of these substances also in their interaction with body functions apparently not directly involved in nociception and pain such as hormone metabolism. Among steroid hormones testosterone was found to be greatly affected by opioids in different experimental and clinical conditions. The purpose of this study was to determine in male rats the effects of a single injection of morphine (5mg/Kg) on persistent pain (formalin test) and their single or combined effect on testosterone plasma and brain levels, and in the changes in mRNA p450-aromatase and 5-a reductase type 1 enzyme levels in the brain, liver and testis. Morphine was assayed in the blood.

Morphine could be detected in the blood of all morphine treated rats notwithstanding no clear analgesic affects could be evidenced in the formalin treated animals three hours after treatment. Testosterone was greatly reduced in the plasma as well as in the brain in morphine treated subjects. In the same morphine-treated rats 5-a reductase activity in the liver and the aromatase activity in the brain and gonads were increased.

From these data it appears that morphine administration can induce long lasting, genomic effects in different body areas supporting the important changes in central and peripheral testosterone depletion. These changes not always were accompanied by behavioral modifications.