Spatial transcriptomics reveals unique molecular fingerprints of human nociceptors

Single-cell transcriptomics on mouse nociceptors has transformed our understanding of pain mechanisms. Equivalent information from human nociceptors is lacking. We used spatial transcriptomics to molecularly characterize transcriptomes of single dorsal root ganglion (DRG) neurons from 8 organ donors. We identified 10 clusters of human sensory neurons, 6 of which are C nociceptors, 1 A{beta} nociceptor, 1 A{delta}, and 2 A{beta} subtypes. These neuron subtypes have distinct expression profiles from rodents and non-human primates and we identify new markers for each of these subtypes that can be applied broadly in human studies. We also identify sex differences, including a marked increase in CALCA expression in female putative itch nociceptors. Our data open the door to new pain targets and unparalleled molecular characterization of clinical sensory disorders.