Interactions between pain sensation, pain unpleasantness, and secondary pain-affect. Interactions are illustrated by arrows. Neural structures likely to have a role in these dimensions are shown. Dashed arrows indicate nociceptive or endogenous physiological factors that influence pain sensation and unpleasantness. ACC, anterior cingulate cortex; PCC, posterior cingulate cortex; IC, insular cortex; HYP, hypothalamus; S1 and S2 , first and second somatosensory cortical areas; PPC, posterior parietal complex; SMA, supplementary motor area; AMYG, amygdala; PFC, prefrontal cortex; RF, reticular formation.