Single-cell RNA sequencing analysis of bone cancer pain model induced by Lewis lung cancer cells in male mice.

Abstract

BACKGROUND: Bone cancer pain (BCP) is one of the most severe complications faced by cancer patients, with complex physiological and pathological mechanisms and unclear molecular characteristics. METHODS: The BCP model was established by inoculating Lewis lung cancer cells into the femur to induce hyperalgesia and spontaneous pain. Single-cell RNA sequencing technology was used to characterize the cell composition and molecular features of the L2-L4 spinal cord after BCP modelling. RESULTS: Our research results identified a total of 10 cell types, namely excitatory neurons, inhibitory neurons, oligodendrocytes, oligodendrocyte precursor cells, Schwann cells, astrocytes, microglia, endothelial cells, fibroblasts, and pericytes. RNA sequencing analysis of the BCP model showed that the proportion of cells in the L2-L4 spinal cord changed significantly, with microglia increased by 45% and oligodendrocytes increased by 43%. Then, data were extracted from microglia, oligodendrocytes, blood-spinal cord barrier component cells (endothelial cells, pericytes, astrocytes), excitatory neurons, and inhibitory neurons, and differential genes were analysed and further enriched. The results suggest that the signalling pathways related to pain perception and transmission and promoting inflammation in the above cells have changed significantly. Finally, this study revealed the interaction between L2-L4 spinal cord cells in BCP. CONCLUSIONS: These data help to understand the molecular mechanism changes caused by BCP and contribute to the development of new treatment methods.