Distinct brainstem to spinal cord noradrenergic pathways differentially regulate spinal neuronal activity

Brainstem to spinal cord pathways modulate spinal neuronal activity. We implemented locus coeruleus (LC) targeting strategies by microinjecting CAV-PRS-ChR2 virus in the spinal cord (LC:SC module) or LC (LC:LC module). While activation of both modules inhibited evoked spinal neuronal firing via α 1 -adrenoceptor-mediated actions, LC:SC opto-activation abolished diffuse noxious inhibitory controls. The LC as a pain generator is likely mechanistically underpinned by maladaptive communication with discrete descending modulatory pathways.