BackgroundFemales are at greater risk of chronic pain, and exhibit higher pain sensitivity compared to males. However, sex differences in conditioned pain modulation (CPM), a neurophysiological risk factor of chronic pain, are unclear. CPM is influenced by many factors, some of which are sex-dependent. This study explored the sex differences in CPM and its biobehavioral determinants, such as blood pressure responses, physical activity levels, pain catastrophizing scores, and conditioning stimulus intensity, in young, healthy, physically active males and females. MethodsTwenty-six males and 24 females completed the CPM test using an electrical pain stimulus and a cold pain stimulus induced via 2 min of cold pressor test. Blood pressure was assessed at baseline and during cold pressor test, whereas cold pain ratings were obtained during cold pressor test to monitor the conditioning stimulus intensity. Physical activity was evaluated via questionnaires and accelerometer, whereas pain catastrophizing was evaluated via a questionnaire. ResultsBoth males and females exhibited CPM, without sex differences in the magnitude of CPM. The males showed higher resting blood pressure, higher physical activity levels, and lower pain catastrophizing scores than the females, without sex differences observed in cold pain ratings and proportion of those who met the physical activity guidelines. No correlations were observed between CPM and its determinants. ConclusionsThe results suggest the complexity of mechanisms underlying the sex differences in CPM. The sex differences in CPM, along with its determinants, may need to be examined in individuals with some risk factors for chronic pain.