Repeated exposure to pain can lead to sensitization of the central nervous system increasing subsequent pain and possibly leading to chronicity. The ability to reverse this sensitization in a top-down manner would be of tremendous clinical benefit but the degree that this can be accomplished volitionally remains unknown. This study investigated whether a brief (∼5 minutes) cognitive-behavioural intervention could change pain perception and reduce central sensitization (as reflected by secondary hyperalgesia). In each of eight sessions, two groups of healthy human subjects received a series of painful thermal stimuli that resulted in secondary hyperalgesia. One group (“Regulate”) was given brief pain-focused cognitive training at each session while the other group (“Control”) received a non-pain focused intervention. The intervention selectively reduced pain unpleasantness but not pain intensity in the Regulate group. Additionally, secondary hyperalgesia was significantly reduced in the Regulate group compared with the Control group. Reduction in secondary hyperalgesia was associated with reduced pain catastrophizing, indicating that changes in central sensitization are related to changes in pain-related cognitions. Thus, the study showed that central sensitization can be modified volitionally by altering pain-related thoughts.