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-evoked 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.