title: Tramadol-induced hyperalgesia and its prevention by ketamine in rats: A randomised experimental study.
abstract: BACKGROUND
  Opioid analgesia not only reduces inhalational anaesthetic requirements but may also induce delayed hyperalgesia, with potential effects on the minimum alveolar concentration (MAC) of inhalational anaesthetics.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the development of tramadol-induced hyperalgesia and the associated changes in MAC, and whether ketamine prevents both processes.
  
  
  METHODS
  A randomised, experimental study.
  
  
  METHODS
  Experimental Surgery Unit, La Paz University Hospital, Madrid, Spain.
  
  
  METHODS
  Thirty-nine adult male Wistar rats.
  
  
  METHODS
  Mechanical nociceptive thresholds (MNT) were determined up to 21 days after the intraperitoneal administration of a single dose of tramadol (50 mg kg) with or without ketamine (10 mg kg), or 0.9% saline. The MNT and the MAC of sevoflurane were also assessed in a second experiment before, early (30 min) and 7 days after drug administration with the same treatments.
  
  
  METHODS
  The MAC and MNT were evaluated. The analysis of variance (ANOVA) test was employed to determine differences between treatments and times on MAC and MNT.
  
  
  RESULTS
  Tramadol, alone or combined with ketamine, produced an early increase in MNT. However, tramadol given alone decreased MNT from day 1 up to 3 weeks, which was associated with an increase in the MAC of sevoflurane (P < 0.05; day 7). Ketamine administration prevented both the reduction in MNT and the increase in MAC (P > 0.05).
  
  
  CONCLUSIONS
  Tramadol-induced hyperalgesia in the rat lasted for several weeks and was associated with an increase in the MAC of sevoflurane. Prior administration of ketamine blocked both phenomena.
authors: From the Department of Animal Medicine and Surgery, Veterinary Faculty, University Complutense (UCM), Madrid, Spain (MA, DA, JB, IAG), Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Centre of Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (MA), Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint Hyacinthe, Quebec, Canada (JB), and Department of Anaesthesiology and Critical Care, Puerta de Hierro University Hospital, Madrid, Spain (JG-F).
authors: Mariana
authors: M
authors: Abreu
authors: Delia
authors: D
authors: Aguado
authors: Javier
authors: J
authors: Benito
authors: Javier
authors: J
authors: García-Fernández
authors: Ignacio A
authors: IA
authors: Gómez de Segura
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics; D000818:Animals; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008738:Methyl Ethers / Q000493:pharmacokinetics; D011650:Pulmonary Alveoli / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D013997:Time Factors; D014147:Tramadol / Q000009:adverse effects*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D014147:Tramadol; D007649:Ketamine