{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:26:34Z","timestamp":1785241594527,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971054"],"award-info":[{"award-number":["81971054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874171"],"award-info":[{"award-number":["81874171"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["JC22022018"],"award-info":[{"award-number":["JC22022018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangsu Qinglan Project, and a project fund of the Basic Scientific Research Program of Nantong City","award":["81971054"],"award-info":[{"award-number":["81971054"]}]},{"name":"Jiangsu Qinglan Project, and a project fund of the Basic Scientific Research Program of Nantong City","award":["81874171"],"award-info":[{"award-number":["81874171"]}]},{"name":"Jiangsu Qinglan Project, and a project fund of the Basic Scientific Research Program of Nantong City","award":["JC22022018"],"award-info":[{"award-number":["JC22022018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phosphorylation of the serine 139 of the histone variant H2AX (\u03b3H2AX) is a DNA damage marker that regulates DNA damage response and various diseases. However, whether \u03b3H2AX is involved in neuropathic pain is still unclear. We found the expression of \u03b3H2AX and H2AX decreased in mice dorsal root ganglion (DRG) after spared nerve injury (SNI). Ataxia telangiectasia mutated (ATM), which promotes \u03b3H2AX, was also down-regulated in DRG after peripheral nerve injury. ATM inhibitor KU55933 decreased the level of \u03b3H2AX in ND7\/23 cells. The intrathecal injection of KU55933 down-regulated DRG \u03b3H2AX expression and significantly induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. The inhibition of ATM by siRNA could also decrease the pain threshold. The inhibition of dephosphorylation of \u03b3H2AX by protein phosphatase 2A (PP2A) siRNA partially suppressed the down-regulation of \u03b3H2AX after SNI and relieved pain behavior. Further exploration of the mechanism revealed that inhibiting ATM by KU55933 up-regulated extracellular-signal regulated kinase (ERK) phosphorylation and down-regulated potassium ion channel genes, such as potassium voltage-gated channel subfamily Q member 2 (Kcnq2) and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in vivo, and KU559333 enhanced sensory neuron excitability in vitro. These preliminary findings imply that the down-regulation of \u03b3H2AX may contribute to neuropathic pain.<\/jats:p>","DOI":"10.3390\/ijms241210148","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T01:32:57Z","timestamp":1686792777000},"page":"10148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nerve Injury-Induced \u03b3H2AX Reduction in Primary Sensory Neurons Is Involved in Neuropathic Pain Processing"],"prefix":"10.3390","volume":"24","author":[{"given":"Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Gong","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Na","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Li","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0912-6171","authenticated-orcid":false,"given":"Jun","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Coral Gables, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Dan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The 1st Clinical Department, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Tao","family":"Deng","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Lu","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Xing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Chun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17448069211056767","DOI":"10.1177\/17448069211056767","article-title":"Epigenetic modifications in neuropathic pain","volume":"17","author":"Luo","year":"2021","journal-title":"Mol. 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