Effects of stress preconditioning on vulnerability of gastric and small intestinal mucosa to ulcerogenic action of indomethacin in rats.

The preconditioning effect of a mild stressor can reduce the ulcerogenic effect of a severe stressor on the gastric mucosa. The aim of the study was to investigate the effect of preconditioning stress on the gastric and the small intestinal injury caused by a single injection of indomethacin (IM) in conscious rats. Preliminary fasting (24 hours) rats were subjected IM administration (35 mg/kg, subcutaneously) with preconditioning stress (30 min cold-restraint at 10°C and further 1 hour keeping in cages at room temperature) or without stress. Plasma corticosterone level, heart rate (HR), blood pressure (BP) and somatic pain sensitivity (tail flick latency) were measured under circumstances of the gastrointestinal IM-induced injury in preliminary stressed and non-stressed rats. IM administration induced formation of gastric erosions well visible 4 hours after its injection. The healing of gastric erosions for 48 hours was accompanied by the development of a small intestinal injury. Corticosterone levels were elevated under formation of gastric erosions (4 hours after IM injection) but decreased following their healing (24 and 48 hours IM injection). Cold-restraint stress caused corticosterone rise 30 min after its onset. IM-induced gastrointestinal injury resulted in an increase of tail flick latencies (somatic hypoalgesia) and gradual decrease of systolic BP and increase of the HR. Stress preconditioning attenuated IM-induced gastric erosions as well as small intestinal injury 4 and 24 hours after its injection, respectively. The preconditioning also resulted in elimination of somatic hypoalgesia 4 hours after IM, but didn't influence an appearance of somatic hypoalgesia 24 and 48 hours after IM. Preconditioning stress recovered the HR and systolic BP (48 hours after IM). Elevated corticosterone level could be observed only in the 4 hour, but not in the 24 and 48 hours after IM administration. Thus, the data suggest that preconditioning stress reduces the vulnerability of the gastric and the small intestinal mucosa to ulcerogenic action of IM, stabilizes the hemodynamic parameters and normalizes somatic pain sensitivity.