Conditioned pain modulation (CPM) (ie, diffuse noxious inhibitory controls) is characterized by reduced perception of pain caused by intense pain in a remote body area. The conditioning stimuli used to trigger CPM causes pain, but also important cardiovascular responses. Higher blood pressure has been associated with reduced pain sensitivity. Descending pain inhibitory mechanisms such as CPM could be involved in this relationship. We investigated the associations between CPM and cardiovascular responses during the cold-pressor test (CPT). Heat pain threshold and tolerance were evaluated in 26 (13 men, 13 women) healthy subjects. CPM was evaluated by comparing pain intensity produced by a 120-second heat stimulation before and after a CPT (5 minutes, 7°C). Heart rate, blood pressure, and baroreflex sensitivity were monitored at rest and during CPT to evaluate cardiovascular responses. We observed a positive relationship between resting blood pressure and heat pain tolerance. The CPT caused important heart rate and blood pressure increases. CPT also reduced pain intensity during the subsequent heat pain-stimulus, indicating effective CPM. A significant positive association was observed between CPM magnitude and the increase in blood pressure during the CPT. These results show that resting blood pressure values are related to acute pain tolerance, while descending pain inhibition is associated with increases in blood pressure. The rise in blood pressure caused by the conditioning stimulus is an important factor predicting the extent of endogenous pain inhibition in healthy subjects.