A synergistic interaction between aspirin, or other non-steroidal anti-inflammatory drugs, and stress which produces severe gastric mucosal damage in rats and pigs.

A synergistic interaction was observed in the development of damage to the gastric mucosa of rats following the administration of a single oral dose of 50 or 200 mg/kg body weight aspirin and exposure to brief periods of cold or restraint stress. Under the experimental conditions employed, the stressed (control) animals did not develop any visible signs of damage while the rats given only aspirin developed typical small erosions. However, the animals given aspirin and simultaneously exposed to stress developed a large number of deep ulcers and massive haemorrhage. Similar results were obtained in rats given a variety of non-steroidal anti-inflammatory drugs, but not with dextropropoxyphene -- an analgesic devoid of ulcerogenic activity. In pigs, the chronic administration of aspirin and exposure to restraint stress resulted in the formation of deep crater-like ulcers. Only small focal lesions were found in the pigs given aspirin alone and no mucosal damage was evident in the pigs exposed only to stress. It appears that the aspirin plus stress synergism may be the basis for the formation of chronic gastric ulcers in humans.