Central Recruitment mechanism of Itch and Pain Through the Paraventricular Thalamic Nucleus in a Pathway- and Intensity-Dependent Manner

The brain is capable of differentiating itch and pain sensations. However, how does the largely overlapped list of nuclei in itch- and pain-matrixes differentially respond to pruriceptive and nociceptive inputs remains unclear. The present study identified distinct recruitment of the central amygdala nucleus (CeA) and the insular cortex (IC), key nodes in both itch- and pain-matrixes, through a parabrachial nucleus (PBN)-paraventricular thalamic nucleus (PVT) pathway that mitigates itch and heightens pain sensations in an intensity-dependent manner. The PVT was divided into discrete functional neuronal ensembles based on morphological, behavioral and electrophysiological evidence. Moreover, lower stimulus intensity was required in PBN-PVT-CeA pathway activation to simulate itch-suppressing effect and induce allodynia than the PBN-PVT-IC pathway. The current work has elucidated the PVT as an essential information sorting nucleus in the thalamus, which might provide a new framework for understanding central nuclei recruitment mechanism of itch and pain.