{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T16:03:37Z","timestamp":1773849817107,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1C1C1005423, 2020R1I1A1A01060928"],"award-info":[{"award-number":["NRF-2020R1C1C1005423, 2020R1I1A1A01060928"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chungnam National University Hospital Research Fund","award":["2018-CF-019"],"award-info":[{"award-number":["2018-CF-019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nuclear factor of activated T cells (NFAT5) is a well-known transcription factor that regulates the expression of genes involved in osmotic stress. However, the role of NFAT5 in inflammatory pain remains unknown. Here, we studied the function of NFAT5 in inflammatory pain using NFAT5-heterozygous (Het) mice. To study inflammatory pain, we injected 10 \u00b5L of 2% formalin into the right hind paws of mice and monitored pain behaviors, such as licking, lifting, and flinching, for 60 min. After the first 15 min (phase I), there were no significant differences in pain behaviors between wild-type (WT) and NFAT5-Het mice. However, from 15\u201360 min (phase II), NFAT5-Het mice displayed significantly fewer pain behaviors compared to WT mice. Further, the expression levels of inflammatory-pain-related factors, including c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated n-methyl-D-aspartate receptor subunit 2B (p-NR2B), were significantly elevated in the spinal dorsal neurons of formalin-treated WT mice but was not elevated in NFAT5-Het mice. Similarly, c-Fos, p-ERK, and p-NR2B levels were significantly higher in glutamate-treated PC12 neuronal cells but were not affected by Nfat5 silencing in glutamate-treated PC12 cells. Altogether, our findings suggest that NFAT5 deficiency may mitigate formalin-induced inflammatory pain by upregulating mammalian target of rapamycin (mTOR) expression and downregulating its downstream factors in spinal dorsal neurons. Therefore, NFAT5 is a potential therapeutic target for the treatment of inflammatory pain.<\/jats:p>","DOI":"10.3390\/ijms22052587","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:39:07Z","timestamp":1614904747000},"page":"2587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["NFAT5 Deficiency Alleviates Formalin-Induced Inflammatory Pain Through mTOR"],"prefix":"10.3390","volume":"22","author":[{"given":"Do Hyeong","family":"Gwon","sequence":"first","affiliation":[{"name":"Department of Medical Science, School of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Anatomy, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song I.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Science, School of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Anatomy, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seoung Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-670X","authenticated-orcid":false,"given":"Yeojung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangwon","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Young","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Physiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-1394","authenticated-orcid":false,"given":"Dong Woon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Science, School of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Anatomy, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4776-4396","authenticated-orcid":false,"given":"Jinpyo","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Physiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6124-5138","authenticated-orcid":false,"given":"Sun Yeul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, School of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3181\/00379727-177-41957","article-title":"Thyroxine and Triiodothyronine in Milk of Cows, Goats, Sheep, and Guinea Pigs","volume":"177","author":"Akasha","year":"1984","journal-title":"Exp. 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