Dynorphinergic projections from the central amygdala to the parabrachial nucleus regulate itch.

The amygdala plays a key role in the processing of itch and pain signals as well as emotion. A previous study revealed that the central nucleus of the amygdala (CeA)-parabrachial nucleus (PBN) pathway is involved in pain regulation. The same pathway might also control itch. To test this possibility, prodynorphin (Pdyn)-Cre mice were used to optogenetically manipulate pdyn + CeA-to-PBN projections. We found that optogenetic stimulation of pdyn + amygdala neurons or pdyn + CeA-to-PBN projections inhibited histamine- and chloroquine-evoked scratching. The number of Fos-positive neurons in the PBN increased following intradermal injection of chloroquine. Optogenetic stimulation of pdyn + CeA-to-PBN projections suppressed the increase in Fos expression in the PBN. Optogenetic stimulation of pdyn + CeA-to-PBN projections increased thermal and mechanical thresholds without affecting anxiety-like behavior. These results highlight the importance of dynorphinergic projections from the central amygdala to the parabrachial nucleus in the regulation of itch signaling. Significance Statement: The central nucleus of the amygdala (CeA)-parabrachial nucleus (PBN) pathway regulates pain signaling. Using prodynorphin (pdyn)-cre mice, we investigated the role of pdyn + CeA-to-PBN projections in itch. Optogenetic stimulation of pdyn + CeA-to-PBN projections inhibited pruritogen-evoked scratching and neuronal activity (c-Fos expression) in the PBN. Together, dynorphinergic projections from the central amygdala to the parabrachial nucleus are important for regulating itch information.