The parietal association cortex and its projections to the dorsal striatum are involved in histaminergic and nonhistaminergic itch processing.

Itch is an unpleasant sensation accompanied by the urge to scratch. The act of scratching not only alleviates the itch but also activates the reward circuitry, inducing a pleasurable sensation that can perpetuate further scratching. Therefore, scratching can be characterized as both a goal-directed behavior and a reward-motivated behavior. As a key hub for sensorymotor integration and information processing in goal-directed tasks, the specific role of the posterior parietal cortex (PPC) in modulating itch remains to be elucidated. Using immunofluorescence and calcium-signal fiber photometric recordings, we found that neurons in the parietal association cortex (PtA), a subregion of the PPC, were activated during acute itch. Pharmacogenetic experiments demonstrated that both nonselective inhibition of neurons in the PtA and selective inhibition of pyramidal neuron activity in the PtA reduced the experimental itch-scratching behavior induced by subcutaneous injections of 5-HT and compound 48/80. The PtA projects to the dorsal striatum (DS), a critical component of the brain's reward circuitry, and inhibition of this pathway also diminished experimental itch-scratching behavior. Therefore, this study demonstrated for the first time that the PtA may be involved in the regulation of the goal-directed behavior of scratching of histaminergic and nonhistaminergic itch through projections to the DS.