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Previous studies suggested that areas of the pain matrix of the human brain are recruited by the processing of pain-related environmental cues such as pain-related pictures or descriptors of pain. However, it is still sketchy whether those activations are specific to the pain-relevance of the stimuli or simply reflect a general effect of negative valence or increased arousal. The present study investigates the neural mechanisms underlying the processing of pain-related, negative, positive, and neutral words. Pain-related words were matched to negative words regarding valence and arousal, and to positive words regarding arousal. Sixteen healthy subjects were scanned during two tasks, imagination and distraction, using functional MRI. When subjects were instructed to image a situation associated with the word presented (imagination task), we found increased activation within dorsolateral prefrontal cortex (DLPFC), inferior patietal gyri (IPG), and precuneus when processing pain-related words compared to other words. However, when attention was focused on a foreground task and words were presented in the background (distraction task), we found a decrease in activation within dorsal anterior cingulum (dACC) and a relative increase in activation within the subgenual ventral anterior cingulum (sACC) when processing pain related words compared to other words. Thus, activations to pain-related words are strongly modulated by the attention demands of the task. Most remarkably, the differences in processing pain-related words compared to non-pain-related words are specific to the pain-relevance of the words and cannot simply be explained by their valence or arousal.