Event-related functional magnetic resonance imaging was used to investigate brain processing of the signals ascending from peripheral C and Adelta fibers evoked by phasic laser stimuli on the right hand in humans. The stimulation of both C and Adelta nociceptors activated the bilateral thalamus, bilateral secondary somatosensory cortex, right (ipsilateral) middle insula, and bilateral Brodmann's area (BA) 24/32, with the majority of activity found in the posterior portion of the anterior cingulate cortex (ACC). However, magnitude of activity in the right (ipsilateral) BA32/8/6, including dorsal parts in the anterior portion of the ACC (aACC) and pre-supplementary motor area (pre-SMA), and the bilateral anterior insula was significantly stronger following the stimulation of C nociceptors than Adelta nociceptors. It was concluded that the activation of C nociceptors, related to second pain, evokes different brain processing from that of Adelta nociceptors, related to first pain, probably due to the differences in the emotional and motivational aspects of either pain, which are mainly related to the aACC, pre-SMA, and anterior insula.