When in pain, pain relief can become a predominant goal. The desire for pain relief is a potent motivator that directs behavior to escape from or reduce potentially harmful stimuli. While the crucial role of pain – at least acute pain – for survival has been widely acknowledged, the rewarding and motivating nature of pain relief has received much less attention. It has been shown that pain relief when perceived as result of active decision making is endogenously enhanced compared to passive receipt of the same nociceptive input, but mechanisms of such effects remain poorly understood. Further, although impaired reward processing has been implicated in the development and maintenance of chronic pain, the exact relationships of exaggerated pain perception and altered reward learning have rarely been tested. We used a probabilistic relief-seeking task to investigate the modulation of pain relief when received as a reward and its role in learning by negative reinforcement. To characterize the underlying psychobiological mechanisms of this modulation we probed the roles of dopaminergic and opioidergic signaling, both of which are implicated in relief processing. Furthermore, we compared relief modulation and effects of reinforcement learning between participants with and without chronic pain. The results indicate that dopaminergic signaling has a key role in modulating the perception of pain relief. The motivationally driven enhancement of pain relief perception appears to be spared by maladaptive changes during pain chronification. These results highlight the important role of motivation and prospective control of behavior for endogenous modulation pain relief.