title: Tropisetron blocks analgesic action of acetaminophen: a human pain model study.
abstract: Because the mechanism underlying the analgesic action of acetaminophen remains unclear, we investigated the possible interaction of acetaminophen with central serotonergic pathways. The effects of acetaminophen, tropisetron, the combination of both drugs, and saline on pain perception and central sensitization in healthy volunteers were compared. Sixteen healthy volunteers were included in this randomized, double-blind, placebo-controlled crossover study. Intracutaneous electrical stimulation (46.1 ± 19.1 mA) induced acute pain (numeric rating scale, 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia and allodynia were regularly assessed before, during, and after a 15-min infusion of acetaminophen, tropisetron, the combination of both drugs, and saline. Acetaminophen concentrations were measured to rule out any pharmacokinetic interaction. Both acetaminophen and tropisetron led to decreased pain ratings as compared to saline. However, when acetaminophen and tropisetron were administered simultaneously, the pain ratings were not affected. There was no significant difference in the evolution of the hyperalgesic and allodynic areas during the study period between the study groups (P = .06 and P = .33, respectively). Acetaminophen serum levels were not significantly different when associated with tropisetron (P = .063), although we observed a trend toward lower acetaminophen concentrations when both drugs were concurrently administered. In summary, while the combination of acetaminophen and tropisetron showed no analgesic action, each drug administered alone led to decreased pain ratings as compared to saline. In an electrically evoked human pain model, the combination of acetaminophen with tropisetron was free of any analgesic potential. However, when administered on its own, both acetaminophen and tropisetron were mildly analgesic.
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, University Hospital Basel, University of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland Department of Anesthesiology, University Hospital Hannover, Hannover, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Bandschapp
authors.forename: Joerg
authors.initials: J
authors.lastname: Filitz
authors.forename: Albert
authors.initials: A
authors.lastname: Urwyler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koppert
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Ruppen
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000627:therapeutic use*; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004558:Electric Stimulation / Q000009:adverse effects; D005542:Forearm / Q000294:innervation; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D007211:Indoles / Q000009:adverse effects*; D008962:Models, Theoretical; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors; D000077526:Tropisetron
chemical_list: D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D007211:Indoles; D000082:Acetaminophen; D000077526:Tropisetron