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Single painful stimuli evoke two successive and qualitatively distinct sensations referred to as first and second pain sensation. Peripherally, the neural basis of this phenomenon is a dual pathway for pain with Adelta and C fibers mediating first and second pain, respectively. Yet, the differential cortical correlates of both sensations are largely unknown. We therefore used magnetoencephalography to record and directly compare first and second pain-related cortical responses to cutaneous laser stimuli in humans. Our results show that brief painful stimuli evoke sustained cortical activity corresponding to sustained pain perception comprising early first pain-related and late second pain-related components. Cortical activity was located in primary (S1) and secondary (S2) somatosensory cortices and anterior cingulate cortex. Time courses of activations disclosed that first pain was particularly related to activation of S1 whereas second pain was closely related to anterior cingulate cortex activation. Both sensations were associated with S2 activation. These results correspond to the different perceptual characteristics of both sensations and probably reflect different biological functions of first and second pain. First pain signals threat and provides precise sensory information for an immediate withdrawal, whereas second pain attracts longer-lasting attention and motivates behavioral responses to limit further injury and optimize recovery.

Cortical representation of first and second pain sensation in humans