The importance of understanding sex differences in patients with clinical pain has spurred investigations of real and potential sex differences in pain transmission and modulation. In pre-clinical and rodent models, differences in basal pain thresholds or sensitivity have been identified with multiple stimuli but these results are often inconsistent, and frequently confounded by test conditions. Although female and male rodents commonly display similar pain thresholds, observed differences in the development, response to and resolution of persistent pain suggest that sex differences may arise in endogenous pain modulation.