Researchers at the Indian Institute of Science (IISc) have mapped a neural circuit that helps explain the intricate relationship between stress and itch, uncovering how specific stress-activated neurons in the brain can directly suppress scratching behaviour. The findings, published in Cell Reports, provide new insight into how emotional states shape sensory perception.
Itch and pain are both aversive sensations triggered by harmful or irritating stimuli, yet they drive very different responses. Pain typically prompts withdrawal — such as pulling a hand away from a hot surface — while itch compels scratching. Although scientists have extensively studied how stress influences pain pathways, the mechanisms linking stress and itch have remained poorly understood, despite clinical observations that stress and anxiety can worsen itch in chronic conditions.
In the new study, the IISc team focused on the lateral hypothalamic area (LHA), a brain region known to regulate stress responses, motivation and emotional states. Using genetically engineered mouse models, they identified a distinct population of neurons within the LHA that become active during acute stress. These stress-sensitive neurons were labelled with fluorescent proteins, allowing researchers to visualise their widespread projections across the brain.
The team then investigated whether activating these neurons would alter itch behaviour. “We ran some pilot experiments, and we saw that surprisingly, acute stress was able to suppress acute itching,” says Jagat Narayan Prajapati, PhD student at the Centre for Neuroscience (CNS), IISc, and first author of the study.
Further experiments confirmed the effect. When researchers artificially stimulated these stress-responsive neurons, scratching behaviour decreased in both short-term chemically induced itch and in a psoriasis-like model of chronic itch. Conversely, silencing the same neurons prevented stress from reducing scratching. Together, the findings demonstrate that this neuronal population is both necessary and sufficient for stress-induced suppression of itch.
“We show that a specific circuit in the lateral hypothalamus can suppress itch during acute stress, revealing how the brain directly links emotional states to sensory perception,” says Arnab Barik, Assistant Professor at CNS and corresponding author. “By identifying the specific neural circuit that links stress to itch, we are opening the possibility of targeting these brain mechanisms to better manage chronic stress-induced worsening of itch.”
The study, conducted in collaboration with PhD student Aynal Haque and Giriraj Sahu, Assistant Professor at the Molecular Biophysics Unit, IISc, also revealed important distinctions between acute and chronic itch. In mice with psoriasis-like chronic inflammation, the same stress-sensitive neurons displayed heightened activity and became more responsive during scratching episodes.
This altered excitability appeared to interfere with their itch-suppressing role, suggesting that under chronic inflammatory conditions, stress-related circuits may become dysregulated. The findings underscore how prolonged stress could worsen itch rather than suppress it.
Chronic itch affects millions worldwide and can significantly impair quality of life. Current therapies largely target the skin and immune system, addressing peripheral symptoms rather than central neural mechanisms. The new findings highlight the brain’s critical role in shaping itch perception.
“Most current treatments for chronic itch are peripheral – they treat the symptoms, not the cause. But the interaction between stress, anxiety, and sensations like itch happens in the brain,” Barik explains. “Understanding these circuits gives us a framework for eventually developing therapies that address the central mechanisms underlying stress-related itch.”
The researchers caution that their experiments examined one specific form of acute stress, and other stress types may engage additional neural circuits. Future studies will focus on identifying the molecular features of these stress-sensitive neurons and exploring how stress-related brain circuits remodel over longer timescales, particularly in chronic disease states.
