The effect of tramadol and indomethacin coadministration on gastric barrier function in dogs

Background: Tramadol is a centrally acting analgesic that is often used in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs). The effect of coadministration of tramadol and indomethacin on gastric barrier function in dogs is unknown. Hypothesis/Objectives: That coadministration of a nonselective NSAID (indomethacin) and tramadol would decrease recovery of barrier function as compared with acid-injured, indomethacin-treated, and tramadol-treated mucosa. Animals: Gastric mucosa of 10 humanely euthanized shelter dogs. Methods: Ex vivo study. Mounted gastric mucosa was treated with indomethacin, tramadol, or both. Gastric barrier function, prostanoid production, and cyclooxygenase expression were quantified. Results: Indomethacin decreased recovery of transepithelial electrical resistance after injury, although neither tramadol nor the coadministration of the two had an additional effect. Indomethacin inhibited production of gastroprotective prostanoids prostaglandin E₂ (acid-injured PGE₂: 509.3±158.3pg/mL, indomethacin+acid injury PGE₂: 182.9±93.8pg/mL, P<.001) and thromboxane B₂ (acid-injured TXB₂: 233.2±90.7pg/mL, indomethacin+acid injury TXB₂: 37.9±16.8pg/mL, P<.001), whereas tramadol had no significant effect (PGE₂ P=.713, TXB₂ P=.194). Neither drug had an effect on cyclooxygenase expression (COX-1 P=.743, COX-2 P=.705). Acid injury induced moderate to marked epithelial cell sloughing, which was unchanged by drug administration. Conclusions and Clinical Importance: There was no apparent interaction of tramadol and a nonselective cyclooxygenase in this ex vivo model. These results suggest that if there is an adverse interaction of the 2 drugs in vivo, it is unlikely to be via prostanoid inhibition.