A research initiative led by KAANG Bong-Kiun, director of the Center for Cognition and Sociality within the Institute for Basic Science (IBS), in collaboration with KO Hyoung-Gon, professor at Kyung Hee University College of Dentistry, has made significant advancements in understanding the neural mechanisms that enable the brain to differentiate between pain and itch sensations within the anterior cingulate cortex (ACC). This study illuminates the specific neural pathways that handle these distinct sensory experiences, marking a significant milestone in neurological research.
Pain and itch, though unpleasant sensations, elicit different responses; pain typically causes withdrawal, while itch leads to scratching. Previously, the scientific community had limited understanding of how the brain processed these sensations distinctly despite their shared neural pathways. These pathways extend from the spinal cord through the thalamus and brainstem, ultimately reaching the ACC. This brain region involves various functions, from basic sensory processing to complex cognitive behaviours. However, the intricacies of how specific neurons within the ACC manage these diverse functions have not been well understood until now. This research provides a clearer picture of how pain and itch information are processed within these neural circuits.
The study involved a detailed analysis of neuronal response patterns in the ACC when exposed to pain and itch stimuli. It revealed two distinct types of neurons: non-selective neurons, which react to both types of stimuli, and stimulus-specific neurons, which respond exclusively to either pain or itch. This categorization is crucial as it indicates that distinct neuronal populations within the ACC manage different sensory experiences, a revelation that deepens our understanding of sensory processing.
The researchers employed the dual-eGRASP technique, a sophisticated synaptic analysis method that Kaang’s team developed to explore these phenomena further. This technique revealed that stimulus-specific neurons in the ACC receive unique synaptic inputs from the mediodorsal thalamus (MD). This discovery supports that pain and itch are processed separately within the brain’s architecture, each through its dedicated neural circuitry.
To validate the functional importance of these neurons, the research team used chemogenetic techniques to deactivate the neurons specific to pain and itch selectively. Suppressing the activity of pain-specific neurons reduced pain perception without affecting itch perception; similarly, deactivating itch-specific neurons diminished itch sensations without altering pain perception. These experiments underscore these neurons’ critical role in shaping our sensory experiences of pain and itch.
This study demonstrates the predetermined roles of ACC neurons in processing sensory information. It establishes that pain- and itch-specific neurons are synaptically connected to corresponding neurons in the MD, thus forming independent neural circuits for each sensation. These findings challenge assumptions about overlapping neural pathways and highlight distinct pathways for processing pain and itch. As the research team continues to explore these neural mechanisms, their work promises to enhance our understanding of sensory processing and potentially lead to more targeted treatments for pain and itch in clinical settings.
More information: Hyoung-Gon Ko et al, Processing of pain and itch information by modality-specific neurons within the anterior cingulate cortex in mice, Nature Communications. DOI: 10.1038/s41467-025-57041-z
Journal information: Nature Communications Provided by Institute for Basic Science
