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Functional magnetic resonance imaging (fMRI) studies have repeatedly demonstrated hyperactivation of canonical nociceptive circuits (e.g., the insula, anterior cingulate cortex, and somatosensory cortices) upon nociceptive stimulation, concomitant with reduced engagement of descending inhibitory pathways, including those involving the periaqueductal gray and rostroventral medulla [27,28]

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doi: 10.1016/j.yfrne.2007.09.001