King's College London

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 α1-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.