PMID- 23229959 OWN - NLM STAT- MEDLINE DCOM- 20140210 LR - 20181202 IS - 1532-2149 (Electronic) IS - 1090-3801 (Linking) VI - 17 IP - 6 DP - 2013 Jul TI - Effects of tapentadol on mechanical hypersensitivity in rats with ligatures of the infraorbital nerve versus the sciatic nerve. PG - 867-80 LID - 10.1002/j.1532-2149.2012.00259.x [doi] AB - BACKGROUND: Convergent data showed that neuropathic pain has specific characteristics at cephalic versus extra-cephalic level, where single-targeted drugs differentially alleviate pain. Because the novel analgesic drug, tapentadol, is acting at two targets, mu-opioid receptors (as agonist) and noradrenaline reuptake (as inhibitor), we tested its effects on neuropathic pain at both cephalic and extra-cephalic levels. METHODS: Sprague-Dawley rats underwent unilateral constriction injury (CCI) to the infraorbital nerve (ION; cephalic territory) or the sciatic nerve (SN; extra-cephalic territory), and alleviation of nerve lesion-induced 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 (ATF3), interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) by repeated tapentadol treatment were quantified by real-time reverse transcription polymerase chain reaction in ganglia and central tissues. RESULTS: Acute administration of tapentadol (1-10 mg/kg, i.p.) significantly reduced allodynia in both CCI-SN and CCI-ION rats. Although morphine (3 mg/kg, s.c.) or reboxetine (10 mg/kg, i.p.) alone was only marginally active, the combination of both drugs produced supra-additive effects like those observed with tapentadol. In contrast to repeated morphine whose effects vanished, the anti-allodynic effects of tapentadol remained unchanged after a 4-day treatment. However, the latter treatment with tapentadol did not affect nerve lesion-evoked overexpression of ATF3, IL-6 and BDNF transcripts. CONCLUSIONS: The dual synergistic pharmacological properties of tapentadol, which result in clear-cut anti-neuropathic pain effects at both cephalic and extra-cephalic levels, probably involve mechanisms downstream of nerve injury-induced neuroinflammatory reaction. CI - (c) 2012 European Federation of International Association for the Study of Pain Chapters. FAU - Michot, B AU - Michot B AD - INSERM U894-CPN, Universite Pierre et Marie Curie, Paris, France. FAU - Bourgoin, S AU - Bourgoin S FAU - Kayser, V AU - Kayser V FAU - Hamon, M AU - Hamon M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121211 PL - England TA - Eur J Pain JT - European journal of pain (London, England) JID - 9801774 RN - 0 (Phenols) RN - 0 (Receptors, Opioid, mu) RN - 76I7G6D29C (Morphine) RN - H8A007M585 (Tapentadol) SB - IM MH - Animals MH - Humans MH - Hyperalgesia/drug therapy MH - Hypersensitivity/*drug therapy MH - Ligation MH - Male MH - Maxillary Nerve/*drug effects/injuries MH - Morphine/therapeutic use MH - Neuralgia/*drug therapy MH - Pain Measurement/methods MH - Phenols/*therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Opioid, mu/metabolism MH - Sciatic Nerve/*drug effects/injuries MH - Tapentadol MH - Treatment Outcome EDAT- 2012/12/12 06:00 MHDA- 2014/02/11 06:00 CRDT- 2012/12/12 06:00 PHST- 2012/11/14 00:00 [accepted] PHST- 2012/12/12 06:00 [entrez] PHST- 2012/12/12 06:00 [pubmed] PHST- 2014/02/11 06:00 [medline] AID - 10.1002/j.1532-2149.2012.00259.x [doi] PST - ppublish SO - Eur J Pain. 2013 Jul;17(6):867-80. doi: 10.1002/j.1532-2149.2012.00259.x. Epub 2012 Dec 11.