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. 2010 Apr;71(2):111–117. doi: 10.1016/j.curtheres.2010.03.001

Effects of naloxone and flumazenil on antinociceptive action of acetaminophen in rats

Halit Madenoğlu 1, Mustafa Kaçmaz 1, Recep Aksu 1,*, Cihangir Bicer 1, Gülay Yaba 2, Karamehmet Yildiz 1, Kudret Doğru 1, Adem Boyaci 1
PMCID: PMC3967277  PMID: 24683257

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).

Conclusion: 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.

Key words: antinociceptive action, acetaminophen (paracetamol), flumazenil, naloxone

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