ArticleScience advances2026
A prefrontal peptidergic circuit for psychogenic itch.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Psychological stress can evoke itch without a peripheral stimulus, yet the underlying mechanism remains undefined. Here, we demonstrate that a peptidergic circuit within the medial prefrontal cortex (mPFC) mediates this phenomenon. In mice under chronic restraint stress, stress-elicited scratching coincided with elevated gastrin-releasing peptide (GRP) release and heightened activity of GRP receptor (GRPR)-expressing neurons in the mPFC. Microinjection of GRP into the mPFC reproduced stress-induced itch, whereas ablation of GRPR neurons abolished it. Optogenetic activation of GRPR neurons or their GRP-expressing inputs from the ventromedial thalamus and basolateral amygdala evoked robust scratching; conversely, silencing these inputs or GRPR neurons attenuated scratching. Collectively, our findings establish a central peptidergic mechanism that transduces psychological stress into pruriceptive output, thereby identifying a critical neural substrate for psychogenic itch.
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