Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying the ‘pain fovea’, we sparsely traced non-peptidergic nociceptors across the body using a newly generated MrgprD CreERT2 mouse line. We found that mouse plantar paw skin also has a low density of MrgprD + neurites, and individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the magnification of plantar paw regions to contribute to the ‘pain fovea’.