Activation of NPY2R-expressing amygdala neurons inhibits itch behavior in mice without lateralization

The central amygdala (CeA) is a crucial hub in the processing of affective itch, containing a diverse array of neuronal populations. Among these components, Neuropeptide Y (NPY) and its receptors, such as NPY2R, affect various physiological and psychological processes. Despite this broad impact, the precise role of NPY2R⁺ CeA neurons in itch modulation remains unknown, particularly concerning any potential lateralization effects. To address this, we employed optogenetics to selectively stimulate NPY2R⁺ CeA neurons in mice, investigating their impact on itch modulation. Optogenetic activation of NPY2R⁺ CeA neurons reduced scratching behavior elicited by pruritogens without exhibiting any lateralization effects. Electrophysiological recordings confirmed increased neuronal activity upon stimulation. However, this modulation did not affect thermal sensitivity, mechanical sensitivity, or formalin-induced hyperalgesia. Additionally, no alterations in anxiety-like behaviors or locomotion were observed upon stimulation. Projection tracing revealed connections of NPY2R⁺ CeA neurons to brain regions implicated in itch processing. Overall, this comprehensive study highlights the role of NPY2R⁺ CeA neurons in itch regulation without any lateralization effects.