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Papers of the Week


Papers: 21 May 2022 - 27 May 2022


Pharmacology/Drug Development


2022 May 20


Am J Pathol

OPIOID USE IN MURINE MODEL RESULTS IN SEVERE GASTRIC PATHOLOGY THAT MAY BE ATTENUATED BY PROTON PUMP INHIBITION.

Authors

Abstract

Opioids are the gold standard for chronic and acute pain management however its consequence on gastric function is relatively understudied. Opioid users have a higher incidence of gastric dysfunction, worse quality of life, increased hospitalizations, and increased use of antiemetic and pain modulator medications. In the current study, we show that morphine treatment in the murine model results in greater disruption of gastric epithelial cell morphology, increased gastric cell apoptosis, elevated inflammatory cytokines and MMP-9 secretion. Morphine treatment also increases gastric acid secretion and causes delays in gastric emptying. Moreover, morphine treatment causes an increase in systemic IL-6 level, which plays an important role in morphine-induced delayed gastric emptying and gastric damage. IL-6KO mice show a significant level of reduction in morphine-induced gastric delaying, acid retention and gastric damage. Thus, morphine-mediated gastric damage is a consequence of the accumulation of acid in the stomach due to increased gastric acid secretion and delayed gastric emptying. Treatment with a proton pump inhibitor resulted in a significant reduction in morphine-induced gastric inflammation, gastric delaying and improved morphine tolerance. Hence, these studies attribute morphine-mediated induction in gastric acidity and inflammatory cytokines as drivers for morphine-associated gastric pathology and show the therapeutic use of proton pump inhibitors as an inexpensive approach for clinical management of morphine-associated pathophysiology and analgesic tolerance.