{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:17:03Z","timestamp":1790655423767,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","award":["K2509181"],"award-info":[{"award-number":["K2509181"]}],"id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004084","name":"Korea Science and Engineering Foundation","doi-asserted-by":"publisher","award":["KOSEF"],"award-info":[{"award-number":["KOSEF"]}],"id":[{"id":"10.13039\/501100004084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["MSIT"],"award-info":[{"award-number":["MSIT"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["Grant"],"award-info":[{"award-number":["Grant"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["NRF\u20102022R1F1A1073548"],"award-info":[{"award-number":["NRF\u20102022R1F1A1073548"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal cord injury (SCI) leads to persistent inflammation, contributing to chronic neuropathic pain. However, current treatments show limited efficacy. Three types of nitric oxide synthase (NOS) play different roles in inflammation and neuronal hyperexcitation. Therefore, this study aimed to determine the predominant NOS subtype involved in neuropathic pain after spinal contusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the effects of intrathecal NOS inhibitors on mechanical sensitivity following a moderate spinal contusion injury in male Sprague\u2010Dawley rats. These NOS inhibitors were N(G)\u2010nitro\u2010L\u2010arginine methyl ester hydrochloride (L\u2010NAME; non\u2010selective NOS inhibitor), 1400W (iNOS inhibitor), N\u03c9\u2010propyl\u2010L\u2010arginine hydrochloride (NPLA; nNOS inhibitor) and N5\u2010(1\u2010iminoethyl)\u2010L\u2010ornithine (L\u2010NIO; eNOS inhibitor). Additionally, we analysed protein expression and cellular localisation of spinal NOS subtypes in rats that underwent SCI or sham procedures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with L\u2010NAME significantly reduced paw withdrawal threshold in a dose\u2010dependent manner, although motor deficits appeared at the highest dose (30\u2009\u03bcM), while 1400W effectively alleviated mechanical hypersensitivity without motor side effects. NPLA showed limited efficacy, and L\u2010NIO had no effect. Protein expression of iNOS increased two\u2010fold in the L4\u20105 spinal segment of SCI rats compared with sham controls. After SCI, iNOS\u2010immunoreactivity colocalized with GFAP in the superficial laminae of the L4\u20105 spinal segment. Treatment with 1400W reduced the hyper\u2010reactivity of both iNOS and GFAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings indicate that iNOS plays a significant role in below\u2010level neuropathic pain following thoracic spinal cord contusion in rats. Specific blockade of iNOS activity may have potential as a therapeutic intervention for spinal\u2010contusion\u2010induced neuropathic pain with reduced risk of side effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>iNOS inhibition effectively alleviated pain without motor side effects, unlike non\u2010selective NOS, nNOS and eNOS inhibitors. The colocalization of iNOS with astrocytes in the spinal cord suggests a key mechanism in pain maintenance. These findings highlight the potential of targeting iNOS as a therapeutic strategy for SCI\u2010induced neuropathic pain with reduced risks of side effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70047","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T03:53:51Z","timestamp":1748058831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Astrocytic Inducible Nitric Oxide Synthase Upregulation Contributes to Chronic Below\u2010Level Neuropathic Pain Following Spinal Cord Injury in Male Rats"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8797-8073","authenticated-orcid":false,"given":"Youngkyung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Physiology Korea University College of Medicine  Seoul Republic of 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