High activity of endogenous opioid system protects against gastric damage development in mouse models of gastric mucosal injury.

Abstract

Gastric mucosal injury appears when acid and pepsin production, simultaneously with inadequate mucosal response, overwhelms protective mechanism in stomach. Here we aimed to explore the linkage between gastric lesion formation and endogenous opioid system activity. Two mouse lines bidirectionally selected for high (HA) and low (LA) swim stress-induced analgesia associated with high and low endogenous opioid system activity were used. Gastric mucosal injury was induced by ethanol (EtOH) and chronic mild stress. To investigate the anti-inflammatory effect of the endogenous opioid system macroscopic score, myeloperoxidase (MPO) activity, the expression of inflammatory molecules as well as oxidative stress markers were determined. Moreover, expression of opioid receptors μ (MOR), κ (KOR) and δ (DOR) at mRNA levels were determined in gastric tissue. High activity of the endogenous opioid system alleviated gastric lesions development in the EtOH-and chronic mild stress-induced mouse gastric mucosal injury models, as demonstrated by decreased macroscopic score in HA line compared to LA. Additionally, antioxidative stress defence mechanisms were positively modulated in both models of gastric mucosal injury. MOR and partially KOR receptors may be responsible for the gastroprotective effect. To our knowledge this is the first study to show that increased activity of the endogenous opioid system prevents from gastric lesion formation by influencing - among others - the anti-inflammatory and anti-oxidant mechanisms in the mice stomach. Hence, we suggest that opioids may play an important role in gastric mucosal injury prevention.