A nociceptive amygdala-striatal pathway for chronic pain aversion

Abstract

AbstractThe basolateral amygdala (BLA) is essential for assigning positive or negative valence to sensory stimuli. Noxious stimuli that cause pain are encoded by an ensemble ofnociceptive BLA projection neurons (BLAnociensemble). However, the role of the BLAnociensemble in mediating behavior changes and the molecular signatures and downstream targets distinguishing this ensemble remain poorly understood. Here, we show that the same BLAnociensemble neurons are required for both acute and chronic neuropathic pain behavior. Using single nucleus RNA-sequencing, we characterized the effect of acute and chronic pain on the BLA and identified enrichment for genes with known functions in axonal and synaptic organization and pain perception. We thus examined the brain-wide targets of the BLAnociensemble and uncovered a previously undescribednociceptive hotspot of the nucleus accumbens shell (NAcSh) that mirrors the stability and specificity of the BLAnociensemble and is recruited in chronic pain. Notably, BLAnociensemble axons transmit acute and neuropathicnociceptive information to the NAcSh, highlighting thisnociceptive amygdala-striatal circuit as a unique pathway for affective-motivational responses across pain states.