Pathogenesis of NSAID-induced gastric damage: Importance of cyclooxygenase inhibition and gastric hypermotility

Figure 15 Working hypothesis on the roles of COX-1 and COX-2 in the pathogenic mechanism of non-steroidal anti-inflammatory drug-induced gastric damage. Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastric hypermotility, followed by microvascular disturbances and neutrophil activation, leading to gastric damage. Gastric hypermotility and subsequent vascular disturbances are associated with a prostaglandin (PG) deficiency caused by COX-1 inhibition. The inhibition of COX-1 up-regulates COX-2 expression, and PGs produced by COX-2 may suppress the neutrophil-endothelial interaction caused by microvascular disturbances due to COX-1 inhibition.