Cortical processing of pain and itch information by distinct neuronal populations

Abstract Pain and itch perception both evoke aversive but qualitatively different feelings. The transmission pathways and brain areas that process pain and itch are related, with the anterior cingulate cortex (ACC) being important for the affective dimension of both sensations. The cellular mechanisms by which these two somatosensory stimuli are processed in the same brain area, however, remain largely unknown. Here we identified distinct neuronal populations related to pain and itch processing in layer II/III of the ACC. These include neurons activated by both itch and pain stimuli separated by a short time interval and modality-specific neurons activated only by either itch or pain stimuli regardless of the interval between them. Using the dual-eGRASP (enhanced green fluorescent protein reconstitution across synaptic partners) technique, we found that pain- and itch-specific neurons preferentially receive synaptic connections from mediodorsal thalamic neurons activated by pain and itch stimuli, respectively. Using an inhibitory designer receptor exclusively activated by a designer drug (DREADD), we found that although suppressing itch- or pain-specific neurons reduced pruriception or nociception, respectively, neither type of inhibition affected the opposite modality. Together, these results indicate that the processing of itch and pain information in the ACC involves activity-dependent and modality-specific neuronal populations, and that pain and itch are processed by functionally distinct ACC neuronal subsets.