Transcriptomic Profiling of Dorsal Root Ganglia in Atopic and Healthy Dogs: A Comparative RNA Sequencing Study with Implications in Cutaneous Itch Research

Background: Itch is a common symptom in skin disorders. While the neural pathways of itch transmission from the skin to the brain are well understood in rodents, the same pathways in dogs remain unclear. The knowledge gap hinders the development of effective treatments for canine itch-related disorders.Hypothesis/Objectives: This study aims to investigate the differential gene expression in the dorsal root ganglia (DRGs) between healthy and atopic dogs to identify specific molecules potentially involved in itch signaling and neuroinflammation in canine atopic dermatitis (AD).Animals: Two atopic and four healthy dogs.Materials and methods: DRGs were collected from atopic and healthy dogs to compare their transcriptional profiles using RNA sequencing.Results: Principal component and heatmap analyses revealed two distinct clusters separating atopic from healthy dogs. Consistent with this observation, we identified 627 (543 up-regulated and 84 down-regulated) differentially-expressed genes (DEGs) in atopic compared to healthy dogs. We further narrowed down our genes of interest to common DEGs in each atopic dog, which revealed 159 (132 up-regulated and 27 down-regulated) DEGs. Among these genes, when we focused on itch-signaling-associated molecules, P2RY12, IL2RG, TLR1, and POSTN were significantly up-regulated, whereas MRGPRD and LPAR3 were significantly down-regulated in both atopic dogs compared to those in healthy dogs. Pathway analysis showed a significant up-regulation of CREB signaling in neurons, myelination signaling, and neuroinflammation signaling pathways in atopic dogs.Conclusions and clinical relevance: Our study suggested that dysregulation of neuroinflammatory pathways might play a role in the pathomechanism of canine AD as in humans.