title: Characterisation of tramadol, morphine and tapentadol in an acute pain model in Beagle dogs.
abstract: OBJECTIVE
  To evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs.
  
  
  METHODS
  Prospective part-randomized pre-clinical research trial.
  
  
  METHODS
  Fifteen male Beagle dogs (HsdCpb:DOBE), aged 12-15 months.
  
  
  METHODS
  On different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg(-1) ), tapentadol (2.15, 4.64, 6.81 mg kg(-1) ) or morphine (0.464, 0.681, 1.0 mg kg(-1) ) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1).
  
  
  RESULTS
  Tapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg(-1) and 0.71 mg kg(-1) , respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociceptive effect of tramadol in this experimental pain model in dogs.
  
  
  CONCLUSIONS
  Different breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states.
authors.affiliation: Grünenthal GmbH, Grünenthal Innovation, Global Preclinical R&D, Aachen, Germany.
authors.forename: Babette
authors.initials: B
authors.lastname: Kögel
authors.forename: Rolf
authors.initials: R
authors.lastname: Terlinden
authors.forename: Johannes
authors.initials: J
authors.lastname: Schneider
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000662:veterinary*; D010636:Phenols / Q000008:administration & dosage / Q000627:therapeutic use*; D017450:Receptors, Opioid, mu / Q000819:agonists; D000077432:Tapentadol; D014147:Tramadol / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D010636:Phenols; D017450:Receptors, Opioid, mu; D014147:Tramadol; D009020:Morphine; D000077432:Tapentadol
keywords: Beagle dog; acute nociceptive pain; morphine; tapentadol; tramadol