{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:13:42Z","timestamp":1760170422447},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2007,12,13]],"date-time":"2007-12-13T00:00:00Z","timestamp":1197504000000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Occupational Health"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:p><jats:bold>Effect of Chronic Topical Exposure to Low\u2010Dose Noxious Chemicals and Stress on Skin Sensitivity in Mice: Yumiko N<jats:sc>akano<\/jats:sc>. Department of Environmental Health, Osaka Prefectural Institute of Public Health<\/jats:bold>\u2014It has been suggested that the recent increase in inflammatory diseases is related to an increase in environmental chemicals and psychiatric stress. To investigate the effect of chronic topical exposure to chemicals and isolation stress, low\u2010dose formalin (a mild contact sensitizer and an irritant), 2,4,6\u2010trinitrochlorobenzene (TNCB; a potent contact sensitizer) and sodium lauryl sulphate (SLS; an irritant) were applied to mouse ears at 7\u2010d intervals under nostress or stress conditions. Skin reactions (ear swelling) elicited by formalin and TNCB increased time dependently. At the chronic stage, a significant skin reaction peaking at 1 h after application was elicited on the formalin\u2010treated sites, while a shift from a delayed\u2010type hypersensitivity to an immediate\u2010type response was observed on the TNCB\u2010treated sites. At the formalin\u2010treated sites, genes related to neurogenic inflammation, i.e., bradykinin (BK) B2 receptor, IL\u20106, and membrane metallo endopeptidase (NEP) mRNA were upregulated. In the TNCB\u2010treated sites, marked upregulation of IFN\u2010\u03b3, IL\u20101\u03b2, IL\u20104, and IL\u20106 mRNA was observed in addition to B2 receptor mRNA. Pretreatment with HOE140, the B2 receptor antagonist suppressed these skin reactions. Increased skin sensitivity to an unrelated chemical, ethanol, and thermal stimuli were elicited in formalin and TNCBtreated mice. Cortisol levels in formalin\u2010treated mice and IgE levels in TNCB\u2010treated mice were elevated respectively. Stress markedly amplified the skin reactions and gene expression related to neurogenic inflammation. SLS did not induce any changes. It was concluded that chronic topical exposure to low\u2010dose noxious chemicals and stress could easily induce skin sensitivity relating to the BK\u2010B2 pathway and nociceptive sensitization reflecting neural sensitization.<\/jats:p>","DOI":"10.1539\/joh.49.431","type":"journal-article","created":{"date-parts":[[2007,12,13]],"date-time":"2007-12-13T05:48:51Z","timestamp":1197524931000},"page":"431-442","source":"Crossref","is-referenced-by-count":9,"title":["Effect of Chronic Topical Exposure to Low\u2010Dose Noxious Chemicals and Stress on Skin Sensitivity in Mice"],"prefix":"10.1093","volume":"49","author":[{"given":"Yumiko","family":"Nakano","sequence":"first","affiliation":[{"name":"Department of Environmental Health Osaka Prefectural Institute of Public Health 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