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TECHNOLOGY, COMPUTING, AND SIMULATION

Ondansetron Inhibits the Analgesic Effects of Tramadol: A Possible 5-HT₃ Spinal Receptor Involvement in Acute Pain in Humans

Roberto Arcioni, MD^*, Marco della Rocca, MD^*, Sarah Romanò, MD^*, Rocco Romano, MD, Paolo Pietropaoli, MD^*, and Alessandro Gasparetto, MD^*

Departments of Anesthesiology, *Institute of Anesthesiology and Intensive Care, Rome University "La Sapienza," Rome; and Institute of Anesthesiology and Intensive Care, Ancona University, Ancona, Italy

Address correspondence and reprint requests to Roberto Arcioni, MD, Via Monte Zeda, 9-00141 Roma, Italia. Address e-mail to r.arcioni{at}virgilio.it

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 (1 mg · mL^-1 · h^-1) for postoperative nausea and vomiting (Group O) 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 O 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 O 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.

IMPLICATIONS: Serotonin is an important neurotransmitter of the descending pathways that down-modulate spinal nociception. In postoperative pain, ondansetron, a selective 5-HT₃ receptor antagonist, increased the analgesic dose of tramadol. We suggest that, when antagonized for antiemetic purpose, 5-HT₃ receptors foster nociception, because of their site-dependent action.

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