Ondansetron does not block tramadol-induced analgesia in mice

Tramadol is a weak opioid agonist and an inhibitor of the reuptake of noradrenaline and serotonin. This study was undertaken to assess a possible pharmacological interaction of ondansetron, a serotonin-3 (5-hydroxytryptamine-3, 5-HT3) antagonist, and tramadol in an animal model for acute pain. Sixty-three male albino mice were randomly given saline, tramadol (10, 20, and 40 mg kg(-1)), ondansetron (1, 2, and 4 mg kg(-1)), or ondansetron (1, 2, and 4 mg kg(-1)) and tramadol (20 mg kg(-1), given 10 min after ondansetron injection) intraperitoneally. Each mouse was assessed twice for tail-flick latency before saline or drug administration and 15, 30, 60, 90, and 120 min thereafter. Tramadol (10 mg kg(-1)) had no effect on pain threshold levels of mice, but tramadol doses of 20 or 40 mg kg(-1) increased pain threshold levels in a dose-dependent manner (p < 0.01 for 20 mg kg(-1) and p < 0.001 for 40 mg kg(-1)). Ondansetron doses of 1, 2, or 4 mg kg(-1) alone had no effect on pain threshold levels of mice. Tramadol (20 mg kg(-1)) and ondansetron (1, 2, and 4 mg kg(-1)) increased pain threshold levels at all doses (p < 0.001 for 1 and 2 mg kg(-1) ondansetron and p < 0.01 for 4 mg kg(-1) ondansetron). The pain threshold levels of mice given tramadol (20 mg kg(-1)) alone or tramadol and ondansetron (p > 0.05 for 1, 2, and 4 mg kg(-1)) were similar. Our results indicate that ondansetron-a 5-HT3 selective antagonist-does not decrease the analgesic effectiveness of tramadol in mice, which may be the result of different mechanisms involving 5-HT3 receptors.