The posterior paraventricular nucleus of the thalamus to nucleus accumbens medial shell circuit mediates an anti-pruritic response

Notable differences between histamine-dependent and histamine-independent itch have been extensively researched at peripheral and spinal levels. However, the way in which the brain processes histamine-dependent and histamine-independent itch remains unknown. We discovered that the posterior paraventricular nucleus of the thalamus (pPVT)→the nucleus accumbens medial shell (NAcMed) circuit exhibits reverse response patterns to histamine-dependent or histamine-independent itch and serves as a central anti-pruritic role. Mechanistically, histamine-dependent itch activates excitatory inputs from the lateral hypothalamus (LH) to mobilise the anti-pruritic centre, thereby buffering its intensity. In cases of chronic itch, however, there is a decrease in the efficiency of the anti-pruritic circuit’s postsynaptic transmission, thereby promoting itch sensitisation. Our research reveals that histamine-dependent and histamine-independent itch are processed differently in the mouse brain, offering insights into the neural mechanisms underlying chronic itch sensitization. Neural mechanisms underlying itch are not fully understood. Here authors show that the pPVT-NAcMed (posterior paraventricular nucleus of the thalamus to nucleus accumbens medial shell) circuit oppositely responds to histamine-dependent vs -independent itch, with LH inputs buffering the former, but chronic itch reduces postsynaptic efficacy, promoting sensitization and revealing differential processing.