Analysis of the circRNA/lncRNA–miRNA–mRNA Networks of Action of Fire Needle Acupuncture in Relieving Chemotherapy-Induced Neuropathic Pain

Purpose: The current treatment strategies of chemotherapy-induced peripheral neuropathy (CIPN) are not ideal. Fire needle acupuncture (FA) has been shown to have significant therapeutic effects on pain, including cancer-related pain. However, the potential mechanisms by which FA alleviates CIPN remain unclear. Methods: A CIPN model was established using oxaliplatin, followed by FA treatment. Mechanical sensitivity in rats was assessed using the paw withdrawal threshold (PWT), and inflammatory cell infiltration in the L4–L6 spinal cord segments was analyzed via hematoxylin and eosin staining. Subsequently, L4–L6 spinal cord segments were collected and whole-transcriptome sequencing and small RNA sequencing were performed to identify differentially expressed genes. PPI networks, circRNAs/lncRNAs–miRNAs–mRNAs, and functional analyses of hub genes were performed to elucidate the potential mechanisms through which FA therapy improves CIPN. Results: FA therapy rapidly increased the PWT and reduced inflammatory infiltration of the spinal cord in CIPN rats. Additionally, 656, 192, 15, and 657 differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs, respectively, were identified as being associated with FA treatment of CIPN. FA treatment is associated with extracellular matrix receptor interactions, the PI3K–Akt and IL-17 pathways. Furthermore, T cells, macrophages, and T follicular helper cells were closely associated with hub genes, suggesting that these immune cells play a pivotal role in the FA-mediated regulation of CIPN. Conclusion: This study elucidates the potential mechanisms by which FA therapy alleviates CIPN. This study provides a direction for future research on FA therapy and lays a theoretical foundation for the clinical application of FA. This leads to data analysis involving whole-transcriptome sequencing and smallRNA sequencing. The analysis includes GO and KEGG analysis, identifying DE-genes, DE-circRNAs, DE-miRNAs and DE-lncRNAs. These elements contribute to constructing a PPI network and CircRNAs/lncRNAs–miRNAs–mRNAs regulatory networks. The process identifies a hub gene, which is linked to immune infiltration. Finally, differential gene expression validation is performed using spinal cord samples analyzed by qRT-PCR.Flowchart of chemotherapy-induced neuropathy treatment and gene expression analysis in rats.