Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain.

Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2004-

Gene Expression*; Chromatin/*metabolism ; Pain/*genetics ; Peripheral Nervous System/*metabolism; Animals ; Disease Models, Animal ; Epigenesis, Genetic ; Ganglia, Spinal/metabolism ; Male ; Pain/metabolism ; Rats ; Rats, Sprague-Dawley ; Transcriptome

Background: Efforts to understand genetic variability involved in an individual's susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms.
Methods: To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system, we used RNA-seq and ATAC-seq of the rat dorsal root ganglion (DRG) to identify novel molecular pathways associated with pain hypersensitivity in two well-studied persistent pain models induced by chronic constriction injury (CCI) of the sciatic nerve and intra-plantar injection of complete Freund's adjuvant (CFA) in rats.
Results: Our RNA-seq studies identify a variety of biological process related to synapse organization, membrane potential, transmembrane transport, and ion binding. Interestingly, genes that encode transcriptional regulators were disproportionately downregulated in both models. Our ATAC-seq data provide a comprehensive map of chromatin accessibility changes in the DRG. A total of 1123 regions showed changes in chromatin accessibility in one or both models when compared to the naïve and 31 shared differentially accessible regions (DAR)s. Functional annotation of the DARs identified disparate molecular functions enriched for each pain model which suggests that chromatin structure may be altered differently following sciatic nerve injury and hind paw inflammation. Motif analysis identified 17 DNA sequences known to bind transcription factors in the CCI DARs and 33 in the CFA DARs. Two motifs were significantly enriched in both models.
Conclusions: Our improved understanding of the changes in chromatin accessibility that occur in chronic pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG.
(© 2021. The Author(s).)

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F32NR015728 United States NR NINR NIH HHS; KL2 TR003108 United States TR NCATS NIH HHS; R01 NS117761 United States NS NINDS NIH HHS; RF1 AG068997 United States AG NIA NIH HHS; R01 GM118760 United States GM NIGMS NIH HHS; R01 NS110598 United States NS NINDS NIH HHS; R01GM118760 United States GM NIGMS NIH HHS; NS110598 United States NS NINDS NIH HHS; F32 NR015728 United States NR NINR NIH HHS; NS117761 United States NS NINDS NIH HHS

Keywords: ATAC-seq; Chromatin accessibility; Dorsal root ganglion; Epigenetics; Inflammation; Nerve injury; Pain; RNA-seq

0 (Chromatin)

Date Created: 20210827 Date Completed: 20220124 Latest Revision: 20240506

20240506

PMC8390277

10.1186/s12974-021-02228-6

34446036