Abstract The basolateral amygdala (BLA) is essential for assigning positive or negative valence to sensory stimuli. Noxious stimuli that cause pain are encoded by an ensemble of noci ceptive BLA projection neurons (BLA noci ensemble). However, the role of the BLA noci ensemble in mediating behavior changes and the molecular signatures and downstream targets distinguishing this ensemble remain poorly understood. Here, we show that the same BLA noci ensemble 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 BLA noci ensemble and uncovered a previously undescribed noci ceptive hotspot of the nucleus accumbens shell (NAcSh) that mirrors the stability and specificity of the BLA noci ensemble and is recruited in chronic pain. Notably, BLA noci ensemble axons transmit acute and neuropathic noci ceptive information to the NAcSh, highlighting this noci ceptive amygdala-striatal circuit as a unique pathway for affective-motivational responses across pain states.

A nociceptive amygdala-striatal pathway for chronic pain aversion