5th Edition of International Neurology Conference 2026

Abstract

Background: Painful diabetic peripheral neuropathy (PDPN) is one of the most common and disabling neurological complications of diabetes mellitus and is characterized by spontaneous pain, mechanical allodynia, and thermal hyperalgesia. Accumulating evidence indicates that abnormal neuronal excitability, neuroinflammation, and neuron–glia interactions within the dorsal root ganglion (DRG) contribute substantially to the initiation and maintenance of diabetic neuropathic pain. Circular RNAs (circRNAs) are a class of stable non-coding RNAs that can regulate gene expression through multiple mechanisms, particularly by acting as competing endogenous RNAs that bind microRNAs (miRNAs). However, the circRNA–miRNA regulatory network involved in PDPN remains incompletely understood. This study aimed to characterize the expression profiles of circRNAs and miRNAs in the DRG of rats with PDPN and to identify potential regulatory networks associated with neuropathic pain.

Methods: A rat model of diabetic peripheral neuropathy was established, and pain-related behavioral changes were evaluated using mechanical withdrawal threshold and thermal nociception tests. Lumbar DRG tissues were collected from experimental and control animals for high-throughput circRNA and miRNA sequencing. Differentially expressed circRNAs and miRNAs were identified according to predefined screening criteria. Potential interactions between circRNAs and miRNAs were predicted based on complementary miRNA response elements, followed by construction of a circRNA–miRNA regulatory network. Candidate miRNA target genes were further predicted, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to explore the biological functions and signaling pathways associated with the identified regulatory networks. Key circRNA–miRNA pairs potentially related to neuroinflammation, neuronal sensitization, and pain signaling were selected for further validation using quantitative real-time polymerase chain reaction.

Results: Rats with PDPN exhibited marked mechanical hypersensitivity and enhanced thermal nociceptive responses, confirming the development of neuropathic pain. Transcriptomic profiling revealed substantial alterations in both circRNA and miRNA expression in the DRG of PDPN rats compared with controls. Integration of differentially expressed circRNAs and miRNAs identified a complex circRNA–miRNA interaction network containing several highly connected candidate regulatory molecules. Functional enrichment analysis showed that the predicted downstream targets were predominantly associated with inflammatory responses, cytokine-mediated signaling, neuronal excitability, synaptic regulation, and intracellular signaling pathways closely related to neuropathic pain, including MAPK, PI3K/Akt, and NF-κB signaling. Several hub circRNAs and miRNAs were identified as potential key regulators of DRG neuroinflammation and peripheral sensitization. The expression patterns of selected candidates were further supported by quantitative validation and were generally consistent with the sequencing results.

Conclusions: PDPN is accompanied by extensive remodeling of the circRNA and miRNA expression landscape in the DRG. Dysregulated circRNA–miRNA interactions may contribute to diabetic neuropathic pain by modulating inflammatory signaling, neuronal excitability, synaptic plasticity, and neuron–glia communication. These findings provide a systematic overview of the non-coding RNA regulatory network in PDPN and identify potential molecular targets for further mechanistic investigation and therapeutic intervention.