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Adv."],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>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)\u2013expressing 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. 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