Analysis of the long non-coding RNA and mRNA expression profiles associated with lidocaine-induced neurotoxicity in the spinal cord of a rat model

Neurotoxicology. 2022 May:90:88-101. doi: 10.1016/j.neuro.2022.03.002. Epub 2022 Mar 10.

Abstract

Neurotoxicity is thought to be one of the causes of lidocaine-associated neurological complications; however, the mechanisms underlying lidocaine-related neurotoxicity are still unclear. Long non-coding RNAs (lncRNAs) are novel mediators of neurotoxicity, and their role in lidocaine-induced neurotoxicity needs to be explored. Here, we established a rat model of lidocaine-induced neurotoxicity via the repetitive intrathecal administration of 10% lidocaine. Thereafter, microarray and bioinformatics analyses were performed to evaluate the changes in lncRNA and mRNA expression profiles in the lumbar spinal cord of the treated rats. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was also employed for verification. The lidocaine-treated rats (group L) showed elevated paw withdrawal threshold (PWT) as well as histopathological injuries in the lumbar spinal cord compared with the control saline-treated rats (group N). Further, relative to group N, microarray analysis showed 179 and 675 differentially expressed lncRNAs (DElncRNAs) and DEmRNAs in the lumbar spinal cord of rats in the group L, respectively. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the DEmRNAs showed that the most significantly enriched functions and pathways were those associated with cell cycle and immuno-inflammatory processes. Furthermore, coding-noncoding co-expression analysis showed multiple lncRNAs that were co-expressed with factors that regulate inflammation. Additionally, by constructing a preliminary competitive endogenous RNA (ceRNA) network analysis, we established a regulatory network of the lncRNAs and mRNAs that are potentially involved in lidocaine-induced neurotoxicity. In conclusion, our findings provide new insights into the molecular mechanisms of lidocaine-induced neurotoxicity; this has significance with respect to the identification of novel therapeutic targets.

Keywords: Bioinformatics analysis; Lidocaine; LncRNA; Neurotoxicity; mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Regulatory Networks
  • Lidocaine / toxicity
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Spinal Cord / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • Lidocaine