title: Influence of tramadol on acute thermal and mechanical cutaneous nociception in dogs.
abstract: OBJECTIVE
  The aim of the study was to evaluate the influence of tramadol on acute nociception in dogs.
  
  
  METHODS
  Experimental, blinded, randomized, crossover study.
  
  
  METHODS
  Six healthy laboratory Beagle dogs.
  
  
  METHODS
  Dogs received three treatments intravenously (IV): isotonic saline placebo (P), tramadol 1 mg kg-1(T1) and tramadol 4 mg kg-1(T4). Thermal thresholds were determined by ramped contact heat stimulation (0.6 °C second-1) at the lateral thoracic wall. Mechanical thresholds (MT) were measured using a probe containing three blunted pins which were constantly advanced over the radial bone, using a rate of force increase of 0.8 N second-1. Stimulation end points were defined responses (e.g. skin twitch, head turn, repositioning, vocalization) or pre-set cut-out values (55 °C, 20 N). Thresholds were determined before treatment and at predetermined time points up to 24 hours after treatment. At each measurement point, blood was collected for determination of O-desmethyltramadol concentrations. The degree of sedation and behavioural side effects were recorded. Data were analysed by one-way anova and two-way anova for repeated measurements.
  
  
  RESULTS
  Thermal nociception was not influenced by drug treatment. Mechanical nociception was significantly increased between P and T1 at 120 and 240 minutes, and between P and T4 at 30, 60, 240 and 420 minutes. T1 and T4 did not differ. O-desmethyltramadol (M1) maximum plasma concentrations (Cmax) were 4.2±0.8 ng mL-1and 14.3±2.8 ng mL-1for T1 and T4, respectively. Times to reach maximum plasma concentrations (Tmax) were 27.6±6.3 minutes for T1 and 32.1±7.8 minutes for T4. No sedation occurred. There were signs of nausea and mild to moderate salivation in both groups.
  
  
  CONCLUSIONS
  Tramadol was metabolized marginally to O-desmethyltramadol and failed to produce clinically relevant acute antinociception. Therefore, the use of tramadol for acute nociceptive pain is questionable in dogs.
authors.affiliation: Clinic for Small Animals, University of Veterinary Medicine, Hannover Foundation, Germany. Electronic address: Alexandra.friederike.schuetter@tiho-hannover.de.
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Schütter
authors.affiliation: Clinic for Small Animals, University of Veterinary Medicine, Hannover Foundation, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Tünsmeyer
authors.affiliation: Clinic for Small Animals, University of Veterinary Medicine, Hannover Foundation, Germany.
authors.forename: Sabine B R
authors.initials: SBR
authors.lastname: Kästner
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D018592:Cross-Over Studies; D004285:Dogs; D059225:Nociception / Q000187:drug effects* / Q000502:physiology; D012867:Skin / Q000187:drug effects*; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D014147:Tramadol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol
keywords: O-desmethyltramadol; antinociception; dog; pain; tramadol