Abstract
As a typical neuropathic pain, post-herpetic neuralgia (PHN) is a common complication of herpes zoster (HZ), which seriously affects the normal life and work of patients. The unclear pathogenesis and lack of effective drugs make the clinical efficacy of PHN unsatisfactory. Here, we obtained the transcriptome profile of neuroblastoma cells (SH-SY5Y) and DRG in rats infected with varicella zoster virus (VZV) by transcriptome sequencing (RNA-Seq) combined with publicly available gene array data sets. Next, the data processing of the transcriptome map was analyzed using bioinformatics methods, including the screening of differentially expressed genes (DEGs), Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the expression of calcium-related genes, and calcium fluorescent probes and calcium colorimetry were used to evaluate the distribution and content of calcium ions in cells after VZV infection. Transcriptome data analysis (GO and KEGG enrichment analysis) showed that calcium disorder played an important role in SH-SY5Y cells infected by VZV and dorsal root ganglion (DRG) of the PHN rat model. The results of qRT-PCR showed that the expression levels of calcium-related genes BHLHA15, CACNA1F, CACNG1, CHRNA9, and STC2 were significantly upregulated, while the expression levels of CHRNA10, HRC, and TNNT3 were significantly downregulated in SH-SY5Y cells infected with VZV. Our calcium fluorescent probe and calcium colorimetric test results showed that VZV could change the distribution of calcium ions in infected cells and significantly increase the intracellular calcium content. In conclusion, our results revealed that the persistence of calcium disorder caused by VZV in nerve cells might be a crucial cause of herpetic neuralgia, and a potential target for clinical diagnosis and treatment of PHN.
Highlights
As a member of the alphaherpesvirinae subfamily, varicella zoster virus (VZV) is a common human pathogen that causes chickenpox during the initial infection, and reactivation from latently infected sensory neurons can cause herpes zoster (HZ) (Oliver et al, 2017; Yang et al, 2017)
Gene Ontology Analysis of differentially expressed genes (DEGs) in SH-SY5Y Cells Infected With VZV
Consistent with the results of Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis showed that the DEGs in dorsal root ganglion (DRG) of herpetic neuralgia rats were mainly enriched in “calcium signaling pathway” (Supplementary Figure 2). These results unanimously indicated that the calcium disorder induced by VZV infection may be involved in the occurrence and development of herpetic neuralgia
Summary
As a member of the alphaherpesvirinae subfamily, varicella zoster virus (VZV) is a common human pathogen that causes chickenpox during the initial infection, and reactivation from latently infected sensory neurons can cause herpes zoster (HZ) (Oliver et al, 2017; Yang et al, 2017). The outbreak of HZ rash usually precedes neuropathic pain, and after the rash is cured, neuropathic pain and discomfort such as allodynia and itching may develop further, eventually resulting in “post-herpetic neuralgia” (PHN) (Oxman et al, 2008). The use of anti-herpes drugs (such as acyclovir and famciclovir) in the early stage of HZ is conducive to shortening the duration of skin lesions and reducing the complications associated with HZ to a certain extent, the pain is unable to be completely cured (Li et al, 2009; Field and Vere Hodge, 2013). Antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs), and sympathetic nerve blockers are commonly used to relieve herpetic neuralgia, but these treatments often fail to prevent the development of PHN (Gan et al, 2013). The lack of precise pathological mechanism and effective drugs makes the clinical treatment of PHN unsatisfactory
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