title: Hyperalgesia and increased sevoflurane minimum alveolar concentration induced by opioids in the rat: a randomised experimental study.
abstract: BACKGROUND
  Perioperative opioids reduce inhalational anaesthetic requirements. The initial hypoalgesia may, however, be followed by a rebound hyperalgesia.
  
  
  OBJECTIVE
  To determine whether prior opioid administration influences inhalational anaesthetic requirements, which might be associated with opioid-induced hyperalgesia.
  
  
  METHODS
  A prospective, randomised, experimental study.
  
  
  METHODS
  Experimental Surgery, La Paz University Hospital, Madrid, Spain.
  
  
  METHODS
  Seventy-nine adult male Wistar rats.
  
  
  METHODS
  Sevoflurane minimum alveolar concentration (MAC) and mechanical nociceptive thresholds (MNTs) were assessed at baseline and 7 days later following opioid treatment with remifentanil 120 μg  kg-1  h-1, buprenorphine 150 μg kg-1, methadone 8 mg  kg-1 or morphine 10 mg  kg-1 The duration of the effect of remifentanil on MAC and MNT was evaluated in addition to the preventive effect of ketamine 10 mg  kg-1 on remifentanil-induced hyperalgesia.
  
  
  METHODS
  The effect of different opioid treatments on MAC and MNT was evaluated using analysis of variance (ANOVA).
  
  
  RESULTS
  All studied opioids produced an immediate reduction in sevoflurane MAC, followed by an increase (16%) in baseline MAC 7 days later (P < 0.05), although the immediate MAC reduction produced by these opioids at that time was not different. Remifentanil produced a decrease in MNT (P < 0.05), which was associated with an increase in the MAC (P < 0.05) that persisted at 21 days. The effect of remifentanil on MNT and MAC was blocked by ketamine.
  
  
  CONCLUSIONS
  Opioid-induced hyperalgesia was associated with an increase in the MAC in normal rats who had not undergone surgery. Both effects lasted 21 days and were prevented by ketamine.
authors.affiliation: From the Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, CCS, Federal University of Rio de Janeiro, Rio de Janeiro, Brasil (MA), Department of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid (UCM), Madrid, Spain (IAGS, DA), Department of Clinical Sciences. Faculty of Veterinary Medicine, University of Montreal (UdM), Saint Hyacinthe, Quebec, Canada (JB) and Department of Anaesthesiology and Critical Care, Puerta de Hierro University Hospital, Madrid, Spain (JGF).
authors.forename: Mariana
authors.initials: M
authors.lastname: Abreu
authors.forename: Delia
authors.initials: D
authors.lastname: Aguado
authors.forename: Javier
authors.initials: J
authors.lastname: Benito
authors.forename: Javier
authors.initials: J
authors.lastname: García-Fernández
authors.forename: Ignacio A Gómez de
authors.initials: IA
authors.lastname: Segura
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000633:toxicity*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002047:Buprenorphine / Q000633:toxicity; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control / Q000523:psychology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008691:Methadone / Q000633:toxicity; D008738:Methyl Ethers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009020:Morphine / Q000633:toxicity; D059225:Nociception / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011897:Random Allocation; D017208:Rats, Wistar; D000077208:Remifentanil; D000077149:Sevoflurane
chemical_list: D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D010880:Piperidines; D000077149:Sevoflurane; D002047:Buprenorphine; D007649:Ketamine; D009020:Morphine; D000077208:Remifentanil; D008691:Methadone