title: Effects of tapentadol on mechanical hypersensitivity in rats with ligatures of the infraorbital nerve versus the sciatic nerve.
abstract: 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, μ-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.
authors.affiliation: INSERM U894-CPN, Université Pierre et Marie Curie, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Michot
authors.forename: S
authors.initials: S
authors.lastname: Bourgoin
authors.forename: V
authors.initials: V
authors.lastname: Kayser
authors.forename: M
authors.initials: M
authors.lastname: Hamon
mesh_terms: D000818:Animals; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D006967:Hypersensitivity / Q000188:drug therapy*; D008026:Ligation; D008297:Male; D008442:Maxillary Nerve / Q000187:drug effects* / Q000293:injuries; D009020:Morphine / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D010636:Phenols / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries; D000077432:Tapentadol; D016896:Treatment Outcome
chemical_list: D010636:Phenols; D017450:Receptors, Opioid, mu; D009020:Morphine; D000077432:Tapentadol