Whole Genomic DNA Methylation Profiling of CpG Sites in Promoter Regions of Dorsal Root Ganglion in Diabetic Neuropathic Pain Mice


DNA methylation and demethylation play an important role in neuropathic pain. In general, DNA methylation of CpG sites in the promoter region impedes gene expression, whereas DNA demethylation contributes to gene expression. Here, we evaluated the methylation status of CpG sites in genomic DNA promoter regions in dorsal root ganglions (DRGs) of diabetic neuropathic pain (DNP) mice. In our research, streptozotocin (STZ) was intraperitoneally injected into mice to construct DNP models. The DNP mice showed higher fasting blood glucose (above 11.1 mmol/L), lower body weight, and mechanical allodynia than control mice. Whole-genome bisulfite sequencing (WGBS) revealed an altered methylation pattern in CpG sites in the DNA promoter regions in DRGs of DNP mice. The results showed 376 promoter regions with hypermethylated CpG sites and 336 promoter regions with hypomethylated CpG sites. In addition, our data indicated that altered DNA methylation occurs primarily on CpG sites in DNA promoter regions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially methylated CpG sites annotated genes were involved in activities of the nervous and sensory systems. Enrichment analysis indicated that genes in these pathways contributed to diabetes or pain. In conclusion, our study enriched the role of DNA methylation in DNP.

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Data Availability

All data and materials described in the study are available from the corresponding author on reasonable request.



Diabetic neuropathic pain


Dorsal root ganglion


Kyoto Encyclopedia of Genes and Genomes


Purinergic P2X ligand-gated ion channel 3 receptor


Paw withdrawal threshold




Whole-genome bisulfite sequencing


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This work was supported by the National Natural Science Foundation of China (grant no. 81971037 to F. Yang, 81870865 to W. Cui), the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ201910025026 to F. Yang), Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan (CIT&TCD201904092 to Q. Li), and Beijing Postdoctoral Research Foundation (grant no. ZZ 2019–01 to W. Chen).

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All authors contributed to the study conception and design. Wen Chen, Fei Yang, and Weihua Cui prepared the manuscript. Wen Chen, Ting Lan, and Qingyu Sun conducted most of the experiments. Yurui Zhang, Danmin Shen, Tingting Hu, Jing Liu, Yingzi Chong, Peipei Wang, and Qian Li analyzed the data and commented on previous publications. All authors approved the final manuscript.

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Correspondence to Fei Yang.

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All animal procedures were approved by the experimental animal ethics committee of Capital Medical University and were performed in accordance with the National Institute of Health Guidelines for the Treatment Animals. The manuscript does not contain any study on human participants.

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Chen, W., Lan, T., Sun, Q. et al. Whole Genomic DNA Methylation Profiling of CpG Sites in Promoter Regions of Dorsal Root Ganglion in Diabetic Neuropathic Pain Mice. J Mol Neurosci (2021). https://doi.org/10.1007/s12031-021-01847-1

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  • Diabetic neuropathic pain
  • DNA methylation
  • Dorsal root ganglion
  • CpG