title: The effects of gabapentin on acute opioid tolerance to remifentanil under sevoflurane anesthesia in rats.
abstract: BACKGROUND
  Tolerance to remifentanil during sevoflurane anesthesia may blunt the ability of this drug to reduce anesthetic requirements. Gabapentin has been shown to be effective in reducing postoperative narcotic usage, a reduction that may be associated with a reduction in opioid-induced tolerance and hyperalgesia. We sought to determine whether gabapentin might prevent the observed acute opioid tolerance (AOT) produced by remifentanil in sevoflurane minimum alveolar concentration (MAC).
  
  
  METHODS
  Wistar rats were anesthetized with sevoflurane and the effects of gabapentin alone on sevoflurane MAC were determined at doses of 150 and 300 mg · kg(-1). In a second experiment, gabapentin 300 mg · kg(-1) was administered before remifentanil (120 and 240 μg · kg(-1) · h(-1)). The MAC was determined before gabapentin administration and 3 more times at 1.5-hour intervals after drug administration to assess AOT. MAC was determined from intratracheal gas samples using a sidestream gas analyzer; tail clamping was used as a supramaximal stimulus. Statistical analysis was performed with the 1-way analysis of variance test.
  
  
  RESULTS
  Remifentanil reduced MAC (2.5 ± 0.2%) by 16% ± 5% and 36% ± 6% (120 and 240 μg · kg(-1) · h(-1), respectively, P < 0.01) with a further reduction produced by coadministration with gabapentin 300 mg · kg(-1) to 39% ± 12% and 62% ± 14%, respectively (P < 0.01 versus remifentanil alone). Gabapentin given alone at 150 and 300 mg · kg(-1) reduced MAC by 26% (both doses, P < 0.01). AOT was observed with remifentanil and characterized by a lower degree of MAC reduction, approximately 1.5 hours later (P < 0.05). However, when remifentanil was administered with gabapentin, the AOT to remifentanil was not observed (P > 0.05).
  
  
  CONCLUSIONS
  Gabapentin reduced the sevoflurane MAC and enhanced the MAC reduction produced by remifentanil. This enhancement may limit AOT in rats.
authors.affiliation: Department of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid, Avda. Puerta de Hierro s/n, 28040 Madrid, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: Aguado
authors.forename: Mariana
authors.initials: M
authors.lastname: Abreu
authors.forename: Javier
authors.initials: J
authors.lastname: Benito
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia-Fernandez
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Gómez de Segura
mesh_terms: D000759:Adjuvants, Anesthesia / Q000008:administration & dosage* / Q000633:toxicity; D000588:Amines / Q000008:administration & dosage*; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000633:toxicity; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D000077206:Gabapentin; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage*; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D000077208:Remifentanil; D000077149:Sevoflurane; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
chemical_list: D000759:Adjuvants, Anesthesia; D000588:Amines; D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D003509:Cyclohexanecarboxylic Acids; D008738:Methyl Ethers; D010880:Piperidines; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000077208:Remifentanil