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A groundbreaking study led by researchers Kaang Bong-Kiun, director of the Center for Cognition and Sociality within the Institute for Basic Science (IBS), and Ko Hyoung-Gon, professor at Kyung Hee University College of Dentistry, has revealed the neural mechanisms responsible for distinguishing pain from itch in the brain’s anterior cingulate cortex (ACC). The study, published in Nature Communications, provides crucial insights into how the brain processes these distinct sensations.
Pain and itch, though both unpleasant, elicit different behavioral responses—pain leads to withdrawal, while itching triggers scratching. Previous studies have struggled to explain how the brain differentiates between these sensations, as they share overlapping neural pathways from the spinal cord to the brain.
Key Findings of the Study
The research team discovered that both pain and itch signals travel through the spinal cord to the thalamus and brainstem before reaching the ACC. This brain region is known for its role in sensory processing and higher-order cognition. However, until now, scientists lacked a clear understanding of how neurons in the ACC manage such diverse functions.
By analyzing neuronal response patterns in the ACC, the researchers identified two distinct types of neurons:
- Non-selective neurons: These responded to both pain and itch stimuli indiscriminately.
- Stimulus-specific neurons: These were exclusively activated by either pain or itch stimuli, but not both.
To further investigate, the team used the dual-eGRASP technique—an advanced synaptic analysis method developed by Kaang’s team in 2018—to show that these stimulus-specific neurons receive distinct inputs from the mediodorsal thalamus (MD). This confirms that pain and itch are processed separately within the ACC by independent neural populations.
Testing the Role of These Neurons
Using chemogenetic techniques, the team selectively deactivated pain- and itch-specific neurons. The results showed that suppressing pain neurons reduced pain perception without affecting itch, and vice versa. This provides strong evidence that these neurons directly shape how we experience pain and itch.
Challenging Conventional Assumptions
The study’s findings challenge the longstanding belief that pain and itch follow overlapping pathways. Instead, the research highlights distinct neural circuits for each sensation. Since the ACC is involved in processing emotional and sensory experiences, these findings suggest that separate neuronal populations encode the subjective experience of pain and itch.
Professor Kaang Bong-Kiun emphasized the importance of the ACC beyond sensory processing, stating, “The ACC is not only crucial for memory storage but also for higher-order emotions such as pain and conflict. This study marks a significant step in understanding emotional memory at the synaptic level.”
Professor Ko Hyoung-Gon, co-corresponding and first author, added, “I’m particularly interested in how these pain- and itch-selective neural circuits change under pathological conditions. Our future research will explore how these circuits interact and how they might be manipulated for therapeutic purposes.”
Future Implications
These findings have significant implications for medical research, particularly in understanding chronic pain and itch conditions. By pinpointing the specific neural pathways involved, researchers may be able to develop targeted treatments for conditions such as chronic pain syndromes and severe itching disorders, improving patient outcomes.
For more details, refer to the published study: Processing of pain and itch information by modality-specific neurons within the anterior cingulate cortex in mice by Hyoung-Gon Ko et al., Nature Communications (2025). DOI: 10.1038/s41467-025-57041-z.
Disclaimer:
This article is based on a recent scientific study and is intended for informational purposes only. It does not constitute medical advice or a diagnosis. Readers should consult healthcare professionals for concerns regarding pain or itch-related conditions.
