Gonadal ERα/β, AR and TRPV1 gene expression: Modulation by pain and morphine treatment in male and female rats

The results of several studies strongly indicate a bidirectional relationship among gonadal hormones and pain. While gonadal hormones play a key role in pain modulation, they have been found to be affected by pain therapies in different experimental and clinical conditions. However, the effects of pain and pain therapy on the gonads are still not clear. In this study, we determined the long-lasting (72 h) effects of inflammatory pain (formalin test) and/or morphine on estrogen receptor (ER), androgen receptor (AR) and TRPV1 gene expression in the rat testis and ovary. The animals were divided into groups: animals receiving no treatment, animals exposed only to the experimental procedure (control group), animals receiving no pain but morphine (sham/morphine), animals receiving pain and morphine (formalin/morphine), and animals receiving only formalin (formalin/saline). Testosterone (T) and estradiol (E) were determined in the plasma at the end of the testing.In the sham/morphine rats, there were increases of ERα, ERβ, AR and TRPV1 mRNA expression in the ovary; in the testis, ERα and ERβ mRNA expression were reduced while AR and TRPV1 expression were unaffected by treatment. T and E plasma levels were increased in morphine-treated female rats, while T levels were greatly reduced in morphine-treated and formalin-treated males.In conclusion, both testicular and ovarian ER (ERα and ERβ) and ovarian AR and TRPV1 gene expression appear to be affected by morphine treatment, suggesting long-lasting interactions among opioids and gonads.

Highlights► Data indicates a bidirectional relationship among gonadal hormones and pain therapy. ► Morphine decreases testosterone in males, the effect being intense and permanent. ► Estradiol, testosterone and their receptors can be significantly changed by morphine.