Ondansetron inhibits the analgesic effects of tramadol:: A possible 5-HT3 spinal receptor involvement in acute pain in humans

To investigate a possible antinociceptive role of serotonin receptor subtype 3 (5-HT3), we evaluated the effects of a coadministration of ondansetron, a 5-HT3 selective antagonist, and tramadol, a central analgesic dependent on enhanced serotonergic transmission. Fifty-nine patients undergoing ear, throat, and nose surgery, using tramadol for 24-h postoperative patient-controlled analgesia (bolus = 30 mg; lockout interval 10 min) were randomly allocated either to a group receiving ondansetron continuous infusion (I mg . mL(-1) . h(-1) ) for postoperative nausea and vomiting (Group 0) or to a control group receiving saline (Group T). Pain and vomiting scores and tramadol consumption were evaluated at 4, 8, 12, and 24 h. Pain scores were never >4, according to a 0-10 numerical rating scale, in both groups. Group 0 required significantly larger doses of tramadol at 4 h (213 versus 71 mg, P < 0.001), 8 h (285 versus 128 mg, P < 0.002), and 12 h (406 versus 190 mg, P < 0.002). Vomiting scores were higher in Group 0 at 4 h (P < 0.05) and 8 h (P = 0.05). We conclude that ondansetron reduced the overall analgesic effect of tramadol, probably blocking spinal 5-HT3 receptors.