How pain emerges from the cortical activity remains an unresolved question in pain neuroscience. A first step toward addressing this question consists in identifying brain activities that occur preferentially in response to painful stimuli in comparison to non-painful stimuli. A key confound that has affected this important comparison in many previous instances is the intensity of the stimuli generating painful and non-painful sensations. Here, we compared the brain activity during iso-intense painful and tactile sensations sampled by functional MRI in 51 healthy participants. Specifically, the perceived intensity was recorded for every stimulus and only the stimuli with rigorously matched perceived intensity were selected and compared between painful and tactile conditions. We found that all brain areas activated by painful stimuli were also activated by tactile stimuli, and vice versa. Neural responses in these areas were correlated with the perceived stimulus intensity, regardless of stimulus modality. More importantly, among these activated areas, we further identified several brain regions showing stronger responses to painful stimuli than to tactile stimuli when perceived intensity was carefully matched, including the bilateral opercular cortex, the left supplementary motor area and the right frontal middle and inferior areas. Among these areas, the right frontal middle area still responded more strongly to painful stimuli even when painful stimuli were perceived less intense than tactile stimuli, whereas other regions now showed stronger responses to tactile stimuli. In contrast, the left postcentral gyrus, the visual cortex, the right parietal inferior gyrus, the left parietal superior gyrus and the right cerebellum were found to have stronger responses to tactile stimuli than to painful stimuli when perceived intensity was carefully matched. When tactile stimuli were perceived less intense than painful stimuli, the left postcentral gyrus and the parietal inferior gyrus still responded more strongly to tactile stimuli while other regions now showed similar responses to painful and tactile stimuli. These results suggest that different brain areas may be engaged differentially when processing painful and tactile information, although their neural activities are not exclusively dedicated to encoding information of only one modality but are also determined by perceived stimulus intensity regardless of stimulus modality.
