title: Effects of naloxone and flumazenil on antinociceptive action of acetaminophen in rats.
abstract: BACKGROUND
  Studies of acetaminophen suggest that multiple nociceptive pathways are involved in the drug's analgesic action.
  
  
  OBJECTIVE
  The purpose of this study was to determine whether naloxone and flumazenil were able to modify or antagonize the antinociceptive effect of acetaminophen in rats.
  
  
  METHODS
  Adult albino Wistar rats were used in the study and randomly allocated to 1 of 4 groups. The acetaminophen group (A group) was administered IP saline and then 300 mg/kg IP acetaminophen 5 minutes thereafter. The acetaminophen + naloxone group (AN group) was pretreated with 1 mg/kg IP naloxone, followed by 300 mg/kg IP acetaminophen 5 minutes later. The acetaminophen + flumazenil group (AF group) was pretreated with 1 mg/kg IP flumazenil, followed by 300 mg/kg IP acetaminophen 5 minutes later. The control group received 2.5 mL IP saline, followed by an additional 2.5 mL IP injection of saline 5 minutes later. The paw-withdrawal latency period of the rats was assessed by an investigator blinded to treatment using the hot-plate test at 30, 45, 60, and 90 minutes after administration of acetaminophen.
  
  
  RESULTS
  Thirty-two rats were evenly randomized by envelope method into 4 groups of 8 rats each. Baseline values for the A, AN, AF, and control groups were not significantly different (9.1 [2.3], 10.5 [2.7], 9.8 [3.0], and 8.9 [1.4] sec, respectively). In the AF group, flumazenil appeared to antagonize the analgesic effect exerted by the acetaminophen in the hot-plate test (30 min, 10.3 [3.7] sec; 45 min, 11.7 [5.1] sec; 60 min, 12.1 [5.1] sec; and 90 min, 12.2 [4.9] sec) and values were not significantly different from those obtained in the control group (30 min, 9.8 [2.2] sec; 45 min, 9.0 [1.6] sec; 60 min, 9.2 [1.6] sec; and 90 min, 8.5 [2.0] sec). In the AN group, naloxone did not significantly affect the values observed in the hot-plate test (30 min, 18.0 [4.5] sec; 45 min, 21.5 [7.8] sec; 60 min, 20.5 [5.9] sec; and 90 min, 22.3 [7.4] sec) and values at all time points were not significantly different from those obtained in the A group (30 min, 17.8 [7.6] sec; 45 min, 20.9 [6.9] sec; 60 min, 21.5 [7.3] sec; and 90 min, 23.8 [8.6] sec). All postbaseline values in the A and AN groups were significantly increased versus baseline and versus the control group values (all, P < 0.05). All postbaseline values in the A group were significantly greater than those in the AF group (all, P < 0.05).
  
  
  CONCLUSIONS
  Flumazenil antagonized the analgesic effect exerted by acetaminophen, while naloxone had no significant effect on acetaminophen's antinociceptive action in this pain model in rats.
authors.affiliation: Department of Anesthesiology and Reanimation, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Halit
authors.initials: H
authors.lastname: Madenoğlu
authors.affiliation: Department of Anesthesiology and Reanimation, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kaçmaz
authors.affiliation: Department of Anesthesiology and Reanimation, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Recep
authors.initials: R
authors.lastname: Aksu
authors.affiliation: Department of Anesthesiology and Reanimation, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Cihangir
authors.initials: C
authors.lastname: Bicer
authors.affiliation: Department of Pharmacology, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Gülay
authors.initials: G
authors.lastname: Yaba
authors.affiliation: Department of Anesthesiology and Reanimation, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Karamehmet
authors.initials: K
authors.lastname: Yildiz
authors.affiliation: Department of Anesthesiology and Reanimation, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Kudret
authors.initials: K
authors.lastname: Doğru
authors.affiliation: Department of Anesthesiology and Reanimation, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Adem
authors.initials: A
authors.lastname: Boyaci
keywords: acetaminophen (paracetamol); antinociceptive action; flumazenil; naloxone