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Department of Oral and Maxillofacial Surgery and Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA

Clinical and experimental studies show serial interactions between the intensity of pain sensation, pain unpleasantness, and secondary emotions associated with reflection and future implications (i.e., suffering). These pain dimensions and their interactions relate to ascending spinal pathways and a central network of brain structures that process nociceptive information both in series and in parallel. Spinal pathways to the amygdala, hypothalamus, reticular formation, medial thalamic nuclei, and limbic cortical structures provide direct inputs to brain areas involved in arousal, bodily regulation, and hence, affect. Another major input to these same structures is from spinal pathways to somatosensory thalamic [ventroposterior lateral (VPL) and ventroposterior medial (VPM)] and cortical areas (S1 , S2 , and the posterior parietal cortex) and from these areas to cortical limbic structures (insular cortex, anterior cingulate cortex). This indirect cortico-limbic pathway integrates pain-perceptive (nociceptive) input with information about overall status of the body and self to provide cognitive mediation of pain affect. Both direct and cortico-limbic pathways converge on the same anterior cingulate cortical and subcortical structures whose function may be to establish emotional valence and response priorities. This entire brain network is under dynamic top-down (neural effects from higher-to-lower levels) modulation by brain mechanisms that are associated with anticipation, expectation, and other cognitive factors.
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