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Because the novel analgesic drug, tapentadol, is acting at two targets, \u03bc\u2010opioid receptors (as agonist) and noradrenaline reuptake (as inhibitor), we tested its effects on neuropathic pain at both cephalic and extra\u2010cephalic levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>prague\u2010<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>awley rats underwent unilateral constriction injury (<jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>) to the infraorbital nerve (<jats:styled-content style=\"fixed-case\">ION<\/jats:styled-content>; cephalic territory) or the sciatic nerve (<jats:styled-content style=\"fixed-case\">SN<\/jats:styled-content>; extra\u2010cephalic territory), and alleviation of nerve lesion\u2010induced mechanical allodynia\/hyperalgesia was assessed after acute or repeated (for 4 days) treatment with tapentadol compared with morphine and\/or reboxetine (noradrenaline reuptake inhibitor) 2 weeks after surgery. Possible changes in the expression of the neuroinflammatory markers activating transcription factor 3 (<jats:styled-content style=\"fixed-case\">ATF<\/jats:styled-content>3), interleukin\u20106 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106) and brain\u2010derived neurotrophic factor (<jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content>) by repeated tapentadol treatment were quantified by real\u2010time reverse transcription polymerase chain reaction in ganglia and central tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Acute administration of tapentadol (1\u201310\u2009mg\/kg, i.p.) significantly reduced allodynia in both<jats:styled-content style=\"fixed-case\">CCI\u2010SN<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">CCI\u2010ION<\/jats:styled-content>rats. Although morphine (3\u2009mg\/kg, s.c.) or reboxetine (10\u2009mg\/kg, i.p.) alone was only marginally active, the combination of both drugs produced supra\u2010additive effects like those observed with tapentadol. In contrast to repeated morphine whose effects vanished, the anti\u2010allodynic effects of tapentadol remained unchanged after a 4\u2010day treatment. However, the latter treatment with tapentadol did not affect nerve lesion\u2010evoked overexpression of<jats:styled-content style=\"fixed-case\">ATF<\/jats:styled-content>3,<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and<jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content>transcripts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The dual synergistic pharmacological properties of tapentadol, which result in clear\u2010cut anti\u2010neuropathic pain effects at both cephalic and extra\u2010cephalic levels, probably involve mechanisms downstream of nerve injury\u2010induced neuroinflammatory reaction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/j.1532-2149.2012.00259.x","type":"journal-article","created":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T11:29:58Z","timestamp":1355225398000},"page":"867-880","source":"Crossref","is-referenced-by-count":20,"title":["Effects of tapentadol on mechanical hypersensitivity in rats with ligatures of the infraorbital nerve versus the sciatic nerve"],"prefix":"10.1002","volume":"17","author":[{"given":"B.","family":"Michot","sequence":"first","affiliation":[{"name":"INSERM U894\u2010CPN Universit\u00e9 Pierre et Marie Curie Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Bourgoin","sequence":"additional","affiliation":[{"name":"INSERM U894\u2010CPN Universit\u00e9 Pierre et Marie Curie Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Kayser","sequence":"additional","affiliation":[{"name":"INSERM U894\u2010CPN Universit\u00e9 Pierre et Marie Curie Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hamon","sequence":"additional","affiliation":[{"name":"INSERM U894\u2010CPN Universit\u00e9 Pierre et Marie Curie Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,12,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21139"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2010.02999.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.10.004"},{"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\/j.bbi.2009.12.002"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"9040","DOI":"10.1523\/JNEUROSCI.20-24-09040.2000","article-title":"Potentiated opioid analgesia in norepinephrine transporter knock\u2010out mice","volume":"20","author":"Bohn L.M.","year":"2000","journal-title":"J Neurosci"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410130209"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00126-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04223"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/S0031-6997(25)06958-3","article-title":"International Union of Pharmacology. 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