title: Rat experimental model of myocardial ischemia/reperfusion injury: an ethical approach to set up the analgesic management of acute post-surgical pain.
abstract: BACKGROUND
  During the past 30 years, myocardial ischemia/reperfusion injury in rodents became one of the most commonly used model in cardiovascular research. Appropriate pain-prevention appears critical since it may influence the outcome and the results obtained with this model. However, there are no proper guidelines for pain management in rats undergoing thoracic surgery. Accordingly, we evaluated three analgesic regimens in cardiac ischemia/reperfusion injury. This study was strongly focused on 3R's ethic principles, in particular the principle of Reduction.
  
  
  METHODS
  Rats undergoing surgery were treated with pre-surgical tramadol (45 mg/kg intra-peritoneal), or carprofen (5 mg/kg sub-cutaneous), or with pre-surgical administration of carprofen followed by 2 post-surgery tramadol injections (multi-modal group). We assessed behavioral signs of pain and made a subjective evaluation of stress and suffering one and two hours after surgery.
  
  
  RESULTS
  Multi-modal treatment significantly reduced the number of signs of pain compared to carprofen alone at both the first hour (61±42 vs 123±47; p<0.05) and the second hour (43±21 vs 74±24; p<0.05) post-surgery. Tramadol alone appeared as effective as multi-modal treatment during the first hour, but signs of pain significantly increased one hour later (from 66±72 to 151±86, p<0.05). Carprofen alone was more effective at the second hour post-surgery when signs of pain reduced to 74±24 from 113±40 in the first hour (p<0.05). Stress behaviors during the second hour were observed in only 20% of rats in the multimodal group compared to 75% and 86% in the carprofen and tramadol groups, respectively (p<0.05).
  
  
  CONCLUSIONS
  Multi-modal treatment with carprofen and tramadol was more effective in preventing pain during the second hour after surgery compared with both tramadol or carprofen. Our results suggest that the combination of carprofen and tramadol represent the best therapy to prevent animal pain after myocardial ischemia/reperfusion. We obtained our results accordingly with the ethical principle of Reduction.
authors.affiliation: Department of Cardiothoracic and Vascular Sciences - Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology, Fondazione IRCCS (IRCCS: Institute for Treatment and Research) Policlinico San Matteo, Pavia, Italy; Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Ciuffreda
authors.affiliation: Surgical Department, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Tolva
authors.affiliation: Surgical Department, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Casana
authors.affiliation: Department of Cardiothoracic and Vascular Sciences - Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology, Fondazione IRCCS (IRCCS: Institute for Treatment and Research) Policlinico San Matteo, Pavia, Italy; Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, Unit of Cardiology, University of Pavia, Pavia, Italy; Department of Medicine, Cape Town University, Cape Town, South Africa.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gnecchi
authors.affiliation: Department of Cardiology, IRCCS Multimedica, Sesto San Giovanni, Milan, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Vanoli
authors.affiliation: Center for Cardiac Arrhythmias of Genetic Base, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Spazzolini
authors.affiliation: Institute of Neuroscience, Comparative Biology Centre, University of Newcastle, Newcastle upon Tyne, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Roughan
authors.affiliation: Laboratory of Cardiac Arrhythmias of Genetic Base, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Calvillo
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002227:Carbazoles / Q000627:therapeutic use; D004195:Disease Models, Animal; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000601:surgery*; D059408:Pain Management / Q000941:ethics*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D017207:Rats, Sprague-Dawley; D014147:Tramadol / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D014147:Tramadol; C007005:carprofen
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