Behavioral and immunohistochemical investigations of the effects of phytoestrogens on pain, analgesia, and inflammation: Gender dependency

The effects of long-term administration of the phytoestrogens (PEs) genistein (Gen) and naringenin (Nar) on nociception, imflammatory hyperalgesia, and metamizol-induced analgesia, the efficacy of PEs vs 17β-E to modulate nociception, as well as the gender dependency of PE effects, and NOS and TH (NO synthase and tyrosine hydroxylase, respectively) expression in the periaqueductal gray (PAG) were studied in gonadectomized female and male rats. The paw pressure, tail flick, and hot plate tests, incapacitance test, and plethismometry were employed for in vivo studies. For in vitro studies, immuno-or histochemical staining of NOS and TH expression in PAG were applied. Data revealed that PEs, like 17β-E, decreased nociceptive thresholds in both sexes, but more significantly in female rats. Genistein intensified carrageenan-induced exudative inflammatory reaction and modulated metamizol-induced analgesia. Long-term PE administration resulted in gender-specific alterations of NO and TH expression. The effects of PEs might be correlated with gender-specific 17β-E-like action in male and female individuals. The results suggest that, similarly to other estrogen-like compounds, PEs can play a significant role in the individualization of analgesic therapy.