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RALY participates in nerve trauma-induced nociceptive hypersensitivity through triggering eIF4G2 gene expression in primary sensory neurons
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  • Lina Huang,
  • Dilip Sharma,
  • Xiaozhou Feng,
  • Zhiqiang Pan,
  • Shaogen Wu,
  • Daisy Munoz,
  • A. Bekker,
  • HuiJuan Hu,
  • Yuan-Xiang Tao
Lina Huang
Rutgers New Jersey Medical School
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Dilip Sharma
Rutgers New Jersey Medical School
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Xiaozhou Feng
Rutgers New Jersey Medical School
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Zhiqiang Pan
Rutgers New Jersey Medical School
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Shaogen Wu
Rutgers New Jersey Medical School
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Daisy Munoz
Rutgers New Jersey Medical School
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A. Bekker
Rutgers New Jersey Medical School
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HuiJuan Hu
Rutgers New Jersey Medical School
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Yuan-Xiang Tao
Rutgers New Jersey Medical School

Corresponding Author:[email protected]

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Abstract

Background and Purpose: Peripheral nerve trauma-induced dysregulation of pain-associated genes in the primary sensory neurons of dorsal root ganglion (DRG) contributes to neuropathic pain genesis. RNA-binding proteins participate in gene transcription. We hypothesized that RALY, an RNA-binding protein, participated in nerve trauma-induced dysregulation of DRG pain-associated genes and nociceptive hypersensitivity. Methods and results: Immunohistochemistry staining showed that RALY was expressed exclusively in the nuclei of DRG neurons. Peripheral nerve trauma caused by chronic constriction injury (CCI) of unilateral sciatic nerve produced time-dependent increases in the levels of Raly mRNA and RALY protein in injured DRG. Blocking this increase through DRG microinjection of adeno-associated virus 5 (AAV5)-expressing Raly shRNA reduced the CCI-induced elevation in the amount of eukaryotic initiation factor 4 gamma 2 (eIF4G2) mRNA and eIF4G2 protein in injured DRG and mitigated the development and maintenance of CCI-induced nociceptive hypersensitivity, without altering basal (acute) response to noxious stimuli and locomotor activity. Mimicking DRG increased RALY through DRG microinjection of AAV5 expressing Raly mRNA upregulated the expression of eIF4G2 mRNA and eIF4G2 protein in the DRG and led to hypersensitive responses to noxious stimuli in the absence of nerve trauma. Mechanistically, CCI promoted the binding of RALY to the promoter of eIF4G2 gene and triggered its transcriptional activity. Conclusion and Implications: Our findings indicate that RALY participates in nerve trauma-induced nociceptive hypersensitivity likely through transcriptionally triggering eIF4G2 expression in the DRG. RALY may be a potential target in neuropathic pain management.
02 Apr 2023Submitted to British Journal of Pharmacology
05 Apr 2023Submission Checks Completed
05 Apr 2023Assigned to Editor
05 Apr 2023Review(s) Completed, Editorial Evaluation Pending
09 Apr 2023Reviewer(s) Assigned
18 Jun 2023Editorial Decision: Revise Minor
29 Aug 20231st Revision Received
30 Aug 2023Submission Checks Completed
30 Aug 2023Assigned to Editor
30 Aug 2023Review(s) Completed, Editorial Evaluation Pending
30 Aug 2023Reviewer(s) Assigned
13 Sep 2023Editorial Decision: Accept