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RNA\u2010binding proteins participate in gene transcription. We hypothesized that RALY, an RNA\u2010binding protein, participated in nerve trauma\u2010induced dysregulation of DRG pain\u2010associated genes and nociceptive hypersensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>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\u2010dependent increases in the levels of <jats:italic>Raly<\/jats:italic> mRNA and RALY protein in injured DRG. Blocking this increase through DRG microinjection of adeno\u2010associated virus 5 (AAV5)\u2010expressing <jats:italic>Raly<\/jats:italic> shRNA reduced the CCI\u2010induced elevation in the amount of eukaryotic initiation factor 4 gamma 2 (<jats:italic>Eif4g2<\/jats:italic>) mRNA and <jats:italic>Eif4g2<\/jats:italic> protein in injured DRG and mitigated the development and maintenance of CCI\u2010induced nociceptive hypersensitivity, without altering basal (acute) response to noxious stimuli and locomotor activity. Mimicking DRG increased RALY through DRG microinjection of AAV5 expressing <jats:italic>Raly<\/jats:italic> mRNA up\u2010regulated the expression of <jats:italic>Eif4g2<\/jats:italic> mRNA and <jats:italic>Eif4g2<\/jats:italic> 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 <jats:italic>Eif4g2<\/jats:italic> gene and triggered its transcriptional activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our findings indicate that RALY participates in nerve trauma\u2010induced nociceptive hypersensitivity likely through transcriptionally triggering <jats:italic>Eif4g2<\/jats:italic> expression in the DRG. RALY may be a potential target in neuropathic pain management.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16259","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T13:34:51Z","timestamp":1696253691000},"page":"735-751","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["RALY participates in nerve trauma\u2010induced nociceptive hypersensitivity through triggering <i>Eif4g2<\/i> gene expression in primary sensory neurons"],"prefix":"10.1111","volume":"181","author":[{"given":"Lina","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, New Jersey Medical School, Rutgers The State University of New Jersey  Newark New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dilip","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, New Jersey Medical School, Rutgers The State University of 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