title: Ondansetron inhibits the analgesic effects of tramadol: a possible 5-HT(3) spinal receptor involvement in acute pain in humans.
abstract: To investigate a possible antinociceptive role of serotonin receptor subtype 3 (5-HT(3)), we evaluated the effects of a coadministration of ondansetron, a 5-HT(3) 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-HT(3) receptors.
  
  
  CONCLUSIONS
  Serotonin is an important neurotransmitter of the descending pathways that down-modulate spinal nociception. In postoperative pain, ondansetron, a selective 5-HT(3) receptor antagonist, increased the analgesic dose of tramadol. We suggest that, when antagonized for antiemetic purpose, 5-HT(3) receptors foster nociception, because of their site-dependent action.
authors.affiliation: Departments of Anesthesiology, Institute of Anesthesiology and Intensive Care, Rome University La Sapienza, Via Monte Zeda, 9-00141 Rome, Italy. r.arcioni@virgilio.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Arcioni
authors.forename: Marco
authors.initials: M
authors.lastname: della Rocca
authors.forename: Sarah
authors.initials: S
authors.lastname: Romanò
authors.forename: Rocco
authors.initials: R
authors.lastname: Romano
authors.forename: Paolo
authors.initials: P
authors.lastname: Pietropaoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gasparetto
mesh_terms: D000208:Acute Disease; D000368:Aged; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D000932:Antiemetics / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000009:adverse effects*; D013517:Otorhinolaryngologic Surgical Procedures; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D020250:Postoperative Nausea and Vomiting / Q000453:epidemiology / Q000517:prevention & control; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D014147:Tramadol / Q000037:antagonists & inhibitors* / Q000627:therapeutic use
chemical_list: D000701:Analgesics, Opioid; D000932:Antiemetics; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D014147:Tramadol; D017294:Ondansetron