Brain Circuits for Pain and Itch Are Separate

A research team led by Kaang Bong-Kiun from the Institute for Basic Science (IBS) and Ko Hyoung-Gon of Kyung Hee University College of Dentistry has uncovered how the brain distinguishes between pain and itch. Their findings, published in Nature Communications, reveal that separate neuronal populations in the anterior cingulate cortex (ACC) selectively process pain and itch, challenging previous assumptions that these sensations share overlapping neural pathways.

How the brain processes pain and itch differently

Pain and itch are distinct sensory experiences – pain typically triggers withdrawal, whereas itch leads to scratching. Both signals travel from the spinal cord to the brain via the thalamus, eventually reaching the ACC, a region involved in sensory processing and cognition. However, how the ACC differentiates these sensations remained unclear.

Using neuronal response analysis, the researchers identified two types of neurons in the ACC:

• Non-selective neurons, which respond to both pain and itch stimuli.
• Stimulus-specific neurons, which are selectively activated by either pain or itch stimuli.

Synaptic mapping reveals independent pain and itch circuits

To explore how these neurons process sensory input, the researchers applied the dual-eGRASP technique, a synaptic analysis method developed by Kaang’s team. They found that stimulus-specific neurons in the ACC receive distinct synaptic inputs from the mediodorsal thalamus (MD). This indicates that pain and itch are processed by separate circuits, rather than a shared pathway.

Further confirmation came from chemogenetic experiments, where researchers selectively deactivated either pain-specific or itch-specific neurons. Suppressing pain neurons reduced pain perception without affecting itch, and vice versa. This suggests that these neurons directly shape how the brain experiences pain and itch, reinforcing the idea of independent processing pathways.

Implications for understanding sensory processing and pain disorders

The study provides new insights into the role of the ACC in mediating the affective aspects of pain and itch. It suggests that these sensory experiences are encoded by distinct neuronal populations, rather than relying on a common processing mechanism.

“The ACC is an important brain area not only for memory storage but also for processing higher-order emotions such as pain and conflict. Through this study, we have taken a step further in understanding emotional memory at the synaptic level.”

Dr. KAANG Bong-Kiun.

Building on these findings, the research team plans to investigate how these neural circuits change in pathological conditions, such as chronic pain or itch disorders. A deeper understanding of these mechanisms could inform future treatments targeting specific neural pathways.

Reference: Ko HG, Jung H, Han S, et al. Processing of pain and itch information by modality-specific neurons within the anterior cingulate cortex in mice. Nat Comm. 2025;16(1):2137. doi: 10.1038/s41467-025-57041-z

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