title: Effects of naloxone on opioid-induced hyperalgesia and tolerance to remifentanil under sevoflurane anesthesia in rats.
abstract: BACKGROUND
  Opioid antagonists at ultra-low doses have been used with opioid agonists to prevent or limit opioid tolerance. The aim of this study was to evaluate whether an ultra-low dose of naloxone combined with remifentanil could block opioid-induced hyperalgesia and tolerance under sevoflurane anesthesia in rats.
  
  
  METHODS
  Male adult Wistar rats were allocated into one of four treatment groups (n = 7), receiving remifentanil (4 µg·kg·min) combined with naloxone (0.17 ng·kg·min), remifentanil alone, naloxone alone, or saline. Animals were evaluated for mechanical nociceptive thresholds (von Frey) and subsequently anesthetized with sevoflurane to determine the baseline minimum alveolar concentration (MAC). Next, treatments were administered, and the MAC was redetermined twice during the infusion. The experiment was performed three times on nonconsecutive days (0, 2, and 4). Hyperalgesia was considered to be a decrease in mechanical thresholds, whereas opioid tolerance was considered to be a decrease in sevoflurane MAC reduction by remifentanil.
  
  
  RESULTS
  Remifentanil produced a significant decrease in mechanical thresholds compared with baseline values at days 2 and 4 (mean ± SD, 30.7 ± 5.5, 22.1 ± 6.4, and 20.7 ± 3.7g at days 0, 2, and 4, respectively) and an increase in MAC baseline values (2.5 ± 0.3, 3.0 ± 0.3, and 3.1 ± 0.3 vol% at days 0, 2, and 4, respectively). Both effects were blocked by naloxone coadministration. However, both remifentanil-treated groups (with or without naloxone) developed opioid tolerance determined by their decrease in MAC reduction.
  
  
  CONCLUSIONS
  An ultra-low dose of naloxone blocked remifentanil-induced hyperalgesia but did not change opioid tolerance under inhalant anesthesia. Moreover, the MAC increase associated with hyperalgesia was also blocked by naloxone.
authors: Department of Animal Medicine and Surgery, University Complutense, Madrid, Spain.
authors: Delia
authors: D
authors: Aguado
authors: Mariana
authors: M
authors: Abreu
authors: Javier
authors: J
authors: Benito
authors: Javier
authors: J
authors: Garcia-Fernandez
authors: Ignacio A
authors: IA
authors: Gómez de Segura
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004361:Drug Tolerance; D006930:Hyperalgesia / Q000139:chemically induced*; D008297:Male; D008738:Methyl Ethers; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077208:Remifentanil; D000077149:Sevoflurane
chemical_list: D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D009292:Narcotic Antagonists; D010880:Piperidines; D009270:Naloxone; D000077149:Sevoflurane; D000077208:Remifentanil