{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T12:55:04Z","timestamp":1762001704800},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,12,5]],"date-time":"2011-12-05T00:00:00Z","timestamp":1323043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies have shown that topiramate, a structurally novel anticonvulsant, exerts antinociceptive activity in animal models of neuropathic, acute somatic, and visceral pain. This study was aimed to examine: (i) the effects of systemically and locally peripherally administered topiramate in the rat inflammatory pain model and (ii) the potential role and site(s) of gamma\u2010aminobutyric acid (GABA), opioid, and adrenergic receptors in topiramate\u2019s antihyperalgesia. Rats received intraplantar (i.pl.) injections of the pro\u2010inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of systemic and local peripheral topiramate on carrageenan\u2010induced hyperalgesia and (ii) the effects of systemic and local peripheral bicuculline (selective GABA<jats:sub>A<\/jats:sub> receptor antagonist), naloxone (nonselective opioid receptor antagonist), and yohimbine (selective \u03b1<jats:sub>2<\/jats:sub>\u2010adrenergic receptor antagonist) on topiramate\u2010induced antihyperalgesia. Systemic topiramate (40\u2013160\u2003mg\/kg; p.o.) produced a significant dose\u2010dependent reduction in the paw inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of systemic topiramate was significantly decreased by systemic bicuculline (0.5\u20131\u2003mg\/kg; i.p.), naloxone (2\u20135\u2003mg\/kg; i.p.), and yohimbine (1\u20133\u2003mg\/kg; i.p.). Local peripheral topiramate (0.03\u20130.34\u2003mg\/paw; i.pl.) also produced significant dose\u2010dependent antihyperalgesia, which was significantly depressed by local peripheral yohimbine (0.05\u20130.2\u2003mg\/paw; i.pl.) but not by local peripheral bicuculline (0.15\u2003mg\/paw; i.pl.) or naloxone (0.1\u2003mg\/paw; i.pl.). The results suggest that topiramate produces systemic and local peripheral antihyperalgesia in an inflammatory pain model, which is, at least partially, mediated by central GABA<jats:sub>A<\/jats:sub> and opioid receptors and by peripheral and most probably central \u03b1<jats:sub>2<\/jats:sub>\u2010adrenergic receptors. These findings contribute to better understanding of topiramate\u2019s action in pain states involving inflammation.<\/jats:p>","DOI":"10.1111\/j.1472-8206.2011.01018.x","type":"journal-article","created":{"date-parts":[[2011,12,5]],"date-time":"2011-12-05T12:11:37Z","timestamp":1323087097000},"page":"319-328","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The mechanisms of antihyperalgesic effect of topiramate in a rat model of inflammatory hyperalgesia"],"prefix":"10.1111","volume":"27","author":[{"given":"Sonja Lj.","family":"Paranos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja A.","family":"Tomi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana M.","family":"Micov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radica M.","family":"Stepanovi\u0107\u2010Petrovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,12,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002508-200301000-00008"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e3283396d6b"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1085-9489.2004.009205.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2006.04.008"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2007.00301.x"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2008.11.005"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e318172b993"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(95)00016-L"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701320"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.07.010"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.04.023"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.06.004"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.02.022"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.09.020"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986707781368469"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.07.004"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/83.3.436"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(83)90201-4"},{"key":"e_1_2_6_20_2","first-page":"409","article-title":"A method for measurement of analgesic activity on inflamed tissue","volume":"111","author":"Randall L.O.","year":"1957","journal-title":"Arch. 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