Neural ensembles that encode affective mechanical and heat pain in mouse spinal cord

Acute pain is an unpleasant experience caused by noxious stimuli. How the spinal neural circuits attribute differences in quality of noxious information remains unknown. By means of genetic capturing, activity manipulation and single cell RNA sequencing, we identified distinct neural ensembles in mouse spinal cord encoding mechanical and heat pain. Re-activation or silencing of these ensembles potentiated or stopped, respectively, affective but not reflex behaviour without altering pain behaviour to cross stimuli modality. Within ensembles, polymodal Gal ⁺ inhibitory neurons with monosynaptic contacts to A-fiber sensory neurons gated affective pain independent of modality. Peripheral nerve injury led to microglia driven inflammation and an ensemble transition with decreased recruitment of Gal ⁺ inhibitory neurons and increased excitatory drive. However, activating Gal ⁺ neurons reversed hypersensitivity associated with neuropathy. Our results reveal the existence of a spinal representation which forms the neural basis of the discriminative and affective qualities of acute pain and that these neurons are under the control of a shared feed-forward inhibition.