The basolateral amygdala decodes visceral pain and itch via distinct circuits and molecules

As aversive sensations, visceral pain and itch are highly refractory to conventional treatments. Accumulating evidence suggests that the basolateral amygdala (BLA) is involved in pain and itch; however, how the BLA segregates visceral pain and itch remains unclear. Here, we identify two distinct neuronal populations within the BLA that selectively respond to visceral pain and itch in mice. These populations project to distinct downstream brain regions-the ventromedial hypothalamus (VMH) and dorsomedial striatum (DMS)-forming separate circuits that specifically regulate visceral pain and itch. Furthermore, function-labeled single cell sequencing demonstrates that Fgf2 and Notch2 are highly and selectively expressed in visceral pain- and itch-labeled neurons, respectively. Knockdown of these genes selectively attenuates visceral pain and itch. These findings emphasize the critical role of the BLA in sorting the processes of visceral pain and itch, providing insights into the neural mechanisms underlying different sensory processing and identifying potential therapeutic targets. The authors find that the basolateral amygdala acts as a critical sorting hub, segregating visceral pain and itch through distinct circuits and molecular markers. This discovery provides a basic framework for sensory research and a neural substrate for targeted therapies.