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However, it is unclear whether other<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content><jats:sub>2<\/jats:sub>receptor ligands have similar effects and whether antinociceptive tolerance develops with repeated treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The Von<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>rey filament test was used to measure mechanical hyperalgesia and the plantar test to measure thermal hyperalgesia in rats injected with complete<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>reund's adjuvant (<jats:styled-content style=\"fixed-case\">CFA<\/jats:styled-content>) treatment or had undergone surgery to induce chronic constriction injury (<jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>), models of inflammatory pain and peripheral neuropathic pain respectively. The effects of morphine and<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content><jats:sub>2<\/jats:sub>receptor ligands, 2\u2010<jats:styled-content style=\"fixed-case\">BFI<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">BU<\/jats:styled-content>224, tracizoline and<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>4056, 3.2\u201332\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.p., on hyperalgesia or affective pain (as measured by a place escape\/avoidance paradigm) were studied in separate experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Morphine and the<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content><jats:sub>2<\/jats:sub>receptor ligands (2\u2010<jats:styled-content style=\"fixed-case\">BFI<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">BU<\/jats:styled-content>224 and tracizoline) all dose\u2010dependently attenuated mechanical and thermal hyperalgesia in<jats:styled-content style=\"fixed-case\">CFA<\/jats:styled-content>\u2010treated rats. The anti\u2010hyperalgesic effects of 2\u2010<jats:styled-content style=\"fixed-case\">BFI<\/jats:styled-content>in<jats:styled-content style=\"fixed-case\">CFA<\/jats:styled-content>\u2010treated and<jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>rats were attenuated by the<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content><jats:sub>2<\/jats:sub>receptor antagonist idazoxan. The combination of 2\u2010<jats:styled-content style=\"fixed-case\">BFI<\/jats:styled-content>and morphine produced additive effects against mechanical hyperalgesia in<jats:styled-content style=\"fixed-case\">CFA<\/jats:styled-content>\u2010treated rats. Repeated treatment (daily for 7\u20139 days) with 2\u2010<jats:styled-content style=\"fixed-case\">BFI<\/jats:styled-content>or<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>4056 did not produce antinociceptive tolerance in<jats:styled-content style=\"fixed-case\">CFA<\/jats:styled-content>\u2010treated or<jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>rats. Morphine and the<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content><jats:sub>2<\/jats:sub>receptor ligands (2\u2010<jats:styled-content style=\"fixed-case\">BFI<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">BU<\/jats:styled-content>224 and<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>4056) were all effective at attenuating place escape\/avoidance behaviour in<jats:styled-content style=\"fixed-case\">CFA<\/jats:styled-content>\u2010treated rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Imidazoline<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content><jats:sub>2<\/jats:sub>receptor ligands have antihyperalgesic effects in rat models of inflammatory and neuropathic pain and may represent a new class of pharmacotherapeutics for the management of chronic pain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12555","type":"journal-article","created":{"date-parts":[[2013,12,13]],"date-time":"2013-12-13T06:46:59Z","timestamp":1386917219000},"page":"1580-1590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Antihyperalgesic effects of imidazoline<scp>I<\/scp><sub>2<\/sub>receptor ligands in rat models of inflammatory and neuropathic pain"],"prefix":"10.1111","volume":"171","author":[{"given":"Jun\u2010Xu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University at Buffalo Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Thorn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University at Buffalo Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University at Buffalo Buffalo NY USA"},{"name":"Department of Physiology School of Basic Medical Sciences Wuhan University Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi\u2010Wen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Basic Medical Sciences Wuhan University Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Triangle Institute Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.03.034"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30303"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2012.01.024"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90209-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(80)90101-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.112.2.205"},{"key":"e_1_2_8_8_1","first-page":"111","article-title":"Analgesic efficacy of CR4056, a novel imidazoline\u20102 receptor ligand, in rat models of inflammatory and neuropathic pain","volume":"4","author":"Ferrari F","year":"2011","journal-title":"J Pain Res"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0219635212500045"},{"key":"e_1_2_8_10_1","first-page":"543","volume-title":"Science of Pain","author":"Gebhart GF","year":"2011"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90026-7"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199606170-00011"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2006.11.077"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2486\/indhealth.2013-0042"},{"key":"e_1_2_8_15_1","unstructured":"JarryC ForfarI BoscJ RenardP ScalbertE GuardiolaB(1997).5\u2010(Arloxymethyl)oxazoline. 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