{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T22:44:16Z","timestamp":1779317056578,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T00:00:00Z","timestamp":1651276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI Grant (2020\u20132022)","award":["8dk0310092h000a"],"award-info":[{"award-number":["8dk0310092h000a"]}]},{"name":"JSPS KAKENHI Grant (2020\u20132022)","award":["R03-Nancho-Ippan"],"award-info":[{"award-number":["R03-Nancho-Ippan"]}]},{"name":"Health and Labour Sciences Research Grant for Research on Rare and Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan, and Tsumura &amp; Co. Ltd.","award":["8dk0310092h000a"],"award-info":[{"award-number":["8dk0310092h000a"]}]},{"name":"Health and Labour Sciences Research Grant for Research on Rare and Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan, and Tsumura &amp; Co. Ltd.","award":["R03-Nancho-Ippan"],"award-info":[{"award-number":["R03-Nancho-Ippan"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Many people are affected by tinnitus, a sensation of ringing in the ear despite the absence of external sound. Goshajinkigan (GJG) is one of the formulations of Japanese traditional herbal medicine and is prescribed for the palliative treatment of patients with tinnitus. Although GJG is clinically effective in these patients, its behavioral effects and the underlying neuroanatomical substrate have not been modeled in animals. We modeled tinnitus using salicylate-treated rats, demonstrated the effectiveness of GJG on tinnitus, and examined the underlying neuronal substrate with c-Fos expression. Intraperitoneal injection of sodium salicylate (400 mg\/kg) into rats for three consecutive days significantly increased false positive scores, which were used to assess tinnitus behavior. When GJG was orally administered one hour after each salicylate injection, the increase in tinnitus behavior was suppressed. The analysis of c-Fos expression in auditory-related brain areas revealed that GJG significantly reduced the salicylate-induced increase in the number of c-Fos-expressing cells in the auditory cortices, inferior colliculus, and dorsal cochlear nucleus. These results suggest a suppressive effect of GJG on salicylate-induced tinnitus in animal models.<\/jats:p>","DOI":"10.3390\/brainsci12050587","type":"journal-article","created":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T05:44:07Z","timestamp":1651297447000},"page":"587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Behavioral and Immunohistochemical Evidence for Suppressive Effects of Goshajinkigan on Salicylate-Induced Tinnitus in Rats"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-5751","authenticated-orcid":false,"given":"Koichi","family":"Kitano","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"},{"name":"Department of Neurophysiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akinori","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taketoshi","family":"Sugimura","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0811-1405","authenticated-orcid":false,"given":"Tadao","family":"Okayasu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaharu","family":"Sakagami","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Osaki","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Kitahara","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-6597","authenticated-orcid":false,"given":"Yasuhiko","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.heares.2016.05.009","article-title":"A systematic review of the reporting of tinnitus prevalence and severity","volume":"337","author":"McCormack","year":"2016","journal-title":"Hear. 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