Translational insights into canine dorsal root ganglia cell types using cross-species comparisons

Abstract

Chronic pain accounts for nearly half of owner-reported canine euthanasia decisions, yet dogs remain underutilized as a large-animal model for studying pain and developing translational therapeutics. Here, we present a canine dorsal root ganglion (DRG) cell atlas generated from six donors, representing five breeds, both sexes, and three spinal segments. Our dataset comprises 3,026 neurons and 11,734 non-neuronal cells and resolves 15 neuronal subtypes that map cleanly onto A- and C-fiber classes. We further identify eight major non-neuronal subtypes, including glial, vascular, and immune populations and characterize neuronal and non-neuronal expression of physiologically relevant neuropeptides, receptors, and ion channels. We identify region-specific differences in subtype composition between lumbar and sacral DRGs, with transcriptional programs suggestive of enhanced tactile-associated signaling in lumbar DRGs and heightened nociception-associated signaling in sacral DRGs. Cross-species comparisons reveal that canine DRG subtypes are broadly conserved with human and mouse, while also exhibiting canine-specific and canine-human shared molecular features relevant for translation. Together, this atlas serves as a valuable resource for understanding canine sensory neurobiology, comparing DRG organization across mammals, and leveraging dogs as a translational model for pain research and therapeutic development.