Processing of pain and itch information by modality-specific neurons within the anterior cingulate cortex in mice

Hyoung-Gon Ko (), Hyunsu Jung, Seunghyo Han, Dong Il Choi, Chiwoo Lee, Ja Eun Choi, Jihae Oh, Chuljung Kwak, Dae Hee Han, Jun-Nyeong Kim, Sanghyun Ye, Jiah Lee, Jaehyun Lee, Kyungmin Lee, Jae-Hyung Lee, Min Zhuo and Bong-Kiun Kaang ()
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Hyoung-Gon Ko: Kyungpook National University
Hyunsu Jung: Institute for Basic Science (IBS)
Seunghyo Han: Kyungpook National University
Dong Il Choi: Seoul National University
Chiwoo Lee: Seoul National University
Ja Eun Choi: Seoul National University
Jihae Oh: Seoul National University
Chuljung Kwak: Institute for Basic Science (IBS)
Dae Hee Han: Institute for Basic Science (IBS)
Jun-Nyeong Kim: Kyungpook National University
Sanghyun Ye: Seoul National University
Jiah Lee: Seoul National University
Jaehyun Lee: Seoul National University
Kyungmin Lee: Kyungpook National University
Jae-Hyung Lee: Kyung Hee University
Min Zhuo: University of Toronto, 1 King’s College Circle
Bong-Kiun Kaang: Institute for Basic Science (IBS)

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Pain and itch are aversive sensations with distinct qualities, processed in overlapping pathways and brain regions, including the anterior cingulate cortex (ACC), which is critical for their affective dimensions. However, the cellular mechanisms underlying their processing in the ACC remain unclear. Here, we identify modality-specific neuronal populations in layer II/III of the ACC in mice involved in pain and itch processing. Using a synapse labeling tool, we show that pain- and itch-related neurons selectively receive synaptic inputs from mediodorsal thalamic neurons activated by pain and itch stimuli, respectively. Chemogenetic inhibition of these neurons reduced pruriception or nociception without affecting the opposite modality. Conversely, activation of these neurons did not enhance stimulus-specific responses but commonly increased freezing-like behavior. These findings reveal 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.

Date: 2025
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DOI: 10.1038/s41467-025-57041-z

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