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Fasting blood glucose measurements and oral glucose tolerance tests were performed to evaluate the effect of agomelatine on glycemia, while metabolic parameters were monitored using metabolic cages. Potential effect of agomelatine on diabetes\u2010induced mechanical and thermal allodynia was evaluated using dynamic plantar aesthesiometer and warm plate (38 \u00b0C) tests, respectively. Additionally, influence of agomelatine on hyperalgesia occurring in connection with diabetic neuropathy was examined using the Randall\u2013Selitto (mechanical nociceptive stimulus), Hargreaves (thermal nociceptive stimulus), and cold plate (4 \u00b0C, thermal nociceptive stimulus) tests. Obtained data indicated that, in diabetic rats, agomelatine significantly improved hyperalgesia and allodynia responses, without no effect on hyperglycemia or the associated polydipsia, polyuria, and hyperphagia. Therapeutic potential of agomelatine on neuropathic pain was suppressed with \u03b1\u2010methyl\u2010para\u2010tyrosine methyl ester (an inhibitor of catecholamine synthesis), phentolamine (a nonselective \u03b1\u2010adrenoceptor antagonist), and propranolol (a nonselective \u03b2\u2010adrenoceptor antagonist) administrations. However, p\u2010chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis) pretreatment could not be achieved to reverse these antihyperalgesic and antiallodynic effects. These results suggest that the curative effect of agomelatine on neuropathic pain is mediated through rising synaptic catecholamine levels as well as through interactions with both \u03b1\u2010 and \u03b2\u2010adrenoceptors. To our knowledge, this is the first study to show findings that indicate catecholaminergic system mediated antihyperalgesic and antiallodynic effects of agomelatine.<\/jats:p>","DOI":"10.1111\/fcp.12224","type":"journal-article","created":{"date-parts":[[2016,7,16]],"date-time":"2016-07-16T08:32:43Z","timestamp":1468657963000},"page":"549-567","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Effect of subacute agomelatine treatment on painful diabetic neuropathy: involvement of catecholaminergic mechanisms"],"prefix":"10.1111","volume":"30","author":[{"given":"Taliha H.","family":"Ayd\u0131n","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy Anadolu University 26470 Eski\u015fehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zg\u00fcr D.","family":"Can","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy Anadolu University 26470 Eski\u015fehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00dcmide","family":"Demir \u00d6zkay","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy Anadolu University 26470 Eski\u015fehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazl\u0131","family":"Turan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy Anadolu University 26470 Eski\u015fehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,5]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.2337\/dc10-S062","article-title":"Diagnosis and classification of diabetes mellitus","volume":"33","author":"American Diabetes Association (A.D.A.)","year":"2010","journal-title":"Diabetes Care"},{"key":"e_1_2_8_3_1","first-page":"130","article-title":"Diabetes mellitus: complications and therapeutics","volume":"12","author":"Tripathi B.K.","year":"2006","journal-title":"Med. 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