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

Pain is an unpleasant experience caused by intense heat or mechanical force. How the spinal cord neural circuits attribute differences in quality of noxious information such as the psychophysically distinct modalities remain unknown. By means of genetic capture, activity manipulation and scRNA sequencing, we identified distinct neural ensembles in the spinal cord encoding mechanical and heat pain. Re-activation or silencing these ensembles potentiated or stopped, respectively, affective but not reflex behaviour without altering pain behaviour to cross stimuli modality. Within ensembles, excitatory neurons encoded quality and a single molecular type of polymodal Gal+ inhibitory neuron type gated affective pain regardless of modality. Following peripheral nerve injury there was a marked circuit-wide molecular perturbation associated with inflammation and the ensembles failed to respect noxious information quality and to resolve allodynia and hypersensitivity in mice. Our results reveal the existence of a spinal representation of cutaneous noxious heat and mechanical stimuli which forms the neural basis of the affective qualities of acute pain perception and that these are under the control of feedforward inhibition by a shared inhibitory neuron type.