Background: Sexual hormones can change nociception in males and females. There are few information about the role of sex hormones on nociception. The aim of this study was to evaluate the effect of endogenous opioids on nociception in male mice compared with female mice during different phases of the estrous cycle (proestrus, estrus, metestrus and diestrus).

Materials and Methods: In this study, adult male and female mice (in different phases of estrous cycle (weighing 30±3gr were assigned to the control group, vehicle and naloxone (3mg/kg, i.p.) groups. In all groups analgesia time was evaluated by hotplate test.

Results: Analgesia time in diestrus phase of control and vehicle groups of female rats was more than the other phases and different from the estrus phase (P<0.05) and male (P<0.001) groups. In the naloxone group, there was a significant reduction in analgesia time among males (P<0.001) and also in the proestrus, estrus, metestrus, diestrus phases (P<0.001, P<0.05, P<0.001, P<0.001, respectively) among females. Moreover, in the naloxone group, a significant difference was seen in analgesia time in male mice compared with females in proestrus and diestrus phases (P<0.05).

Conclusion: It seems that the effects of sex hormones in male and female mice on pain perception mechanisms can be mediated by endogenous opioids.