Abstract
INTRODUCTION: Microglia and astrocytes are believed to play a central role in the pathogenesis of neuropathic pain (NeP). These glial cells are commonly identified by the expression of ionized calcium-binding adaptor molecule 1 (IBA1) for microglia and glial fibrillary acidic protein (GFAP) for astrocytes. Under pathological conditions, astrocytes and microglia undergo both morphological and transcriptional changes, which may promote shifts in functions that can have both protective and detrimental effects on the surrounding neuroparenchyma. Like humans, the dog breed Cavalier King Charles Spaniels (CKCSs) suffers from heritable syringomyelia (SM) which in both species is associated with NeP. OBJECTIVES: To investigate the potential role of IBA1 and GFAP-positive cells in the dorsal horn in CKCSs with SM and NeP. METHODS: Using NanoString GeoMx technology, we conducted spatial transcriptomic analyses on spinal cord dorsal horns from CKCSs with SM and NeP. RESULTS: Several differentially expressed genes were identified in dogs with SM and NeP. Cells positive for IBA1 showed upregulation of inflammatory genes as well as a downregulation of immune functions, while GFAP-positive cells indicated different states of reactivity. Pathway analyses indicated that the PI3K-Akt signaling pathway may be involved in the generation of NeP in CKCSs with SM. CONCLUSION: These findings provide new insights into the complex molecular changes in dorsal horn IBA1 and GFAP-rich areas in the presence of NeP and SM. The findings of this study serve as a foundation for future research that may facilitate new understandings of NeP mechanisms.