Pain and relief are at opposite ends of the reward–aversion continuum. Studying them provides an opportunity to evaluate dynamic changes in brain activity in reward–aversion pathways as measured by functional magnetic resonance imaging (fMRI). Of particular interest is the nucleus accumbens (NAc), a brain substrate known to be involved in reward–aversion processing, whose activation valence has been observed to be opposite in response to reward or aversive stimuli. Here we have used pain onset (aversive) and pain offset (rewarding) involving a prolonged stimulus applied to the dorsum of the hand in 10 male subjects over 120s to study the NAc fMRI response. The results show a negative signal change with pain onset and a positive signal change with pain offset in the NAc contralateral to the stimulus. The study supports the idea that the NAc fMRI signal may provide a useful marker for the effects of pain and analgesia in healthy volunteers.