Anticipation of pain is a complex state that may influence the perception of subsequent noxious stimuli. We used functional magnetic resonance imaging (fMRI) to study changes of activity of cortical nociceptive networks in healthy volunteers while they expected the somatosensory stimulation of one foot, which might be painful (subcutaneous injection of ascorbic acid) or not. Subjects had no previous experience of the noxious stimulus. Mean fMRI signal intensity increased over baseline values during anticipation and during actual stimulation in the putative foot representation area of the contralateral primary somatosensory cortex (SI). Mean fMRI signals decreased during anticipation in other portions of the contralateral and ipsilateral SI, as well as in the anteroventral cingulate cortex. The activity of cortical clusters whose signal time courses showed positive or negative correlations with the individual psychophysical pain intensity curve was also significantly affected during the waiting period. Positively correlated clusters were found in the contralateral SI and bilaterally in the anterior cingulate, anterior insula, and medial prefrontal cortex. Negatively correlated clusters were found in the anteroventral cingulate bilaterally. In all of these areas, changes during anticipation were of the same sign as those observed during pain but less intense ( approximately 30-40% as large as peak changes during actual noxious stimulation). These results provide evidence for top-down mechanisms, triggered by anticipation, modulating cortical systems involved in sensory and affective components of pain even in the absence of actual noxious input and suggest that the activity of cortical nociceptive networks may be directly influenced by cognitive factors.
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