Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response

The lateral parabrachial nucleus (lPBN) is a major target of spinal projection neurons conveying nociceptive input into supraspinal structures. However, the functional role of distinct lPBN efferents for diverse nocifensive responses have remained largely uncharacterized. Here, we show that two populations of efferent neurons from different regions of the lPBN collateralize to distinct targets. Activation of efferent projections to the ventromedial hypothalamus (VMH) or lateral periaqueductal gray (lPAG) drive escape behaviors, whereas the activation of lPBN efferents to the bed nucleus stria terminalis (BNST) or central amygdala (CEA) generates an aversive memory. Finally, we provide evidence that dynorphin expressing neurons span cytoarchitecturally distinct domains of the lPBN to coordinate these distinct aspects of the nocifensive response.