Morphine as a drug for stress ulcer prevention and healing in the stomach
Introduction
It has been suggested that endogenous opioids released during stress may attenuate the pathological effects of stress. Indeed, morphine treatment prior to cold-restraint stress reduced ulcer severity (Glavin, 1985). It was postulated to be due to the activation of kappa opioid receptor (Ray et al., 1993) and induction of prostaglandin production in the gastric mucosa (Ferri et al., 1983). However, blockade of the opioid receptor gave controversial effects. It was reported that opioid receptor antagonists could worsen gastric ulceration Glavin, 1985, Arrigo-Reina and Ferri, 1980. Other report showed that these blockers protected against the formation of stress ulcer in the stomach Morley et al., 1982, Dai and Chan, 1983. How exactly opioid receptor involves in stress ulceration and the mechanisms underlying these actions are yet to be defined. Moreover, there is no report concerning the action of morphine on ulcer healing after ulcer is formed. This action could be equally important as far as the clinical implication for morphine is concerned because patients, especially after surgery, are under different kinds of stress conditions in which complications such as gastric injury and bleeding would likely occur (McGuigan, 1991). Such therapeutic indication is interesting and requires further study. We aim to study whether morphine is effective to prevent ulceration and promote ulcer healing in the stomach in stress conditions. These actions, if any, could likely be due to the strengthening of the defensive mechanisms and increasing the repair system, respectively, in the gastric mucosa.
Section snippets
Animals
Male Sprague–Dawley rats, weighing 200–230 g, were obtained from the Laboratory Animal Unit of the University of Hong Kong. The animals were housed in cages with wide mesh wire bottoms to prevent coprophagy and fed a standard laboratory diet and given free access to tap water. The cages were kept in a room with controlled temperature (22±1 °C), relative humidity (65–70%) and day/night cycle (12:12 light/dark). The protocols of the following experiments were approved by the Committee on the Use
Effects of morphine pre- and posttreatment on stress-induced gastric mucosal damage and its influence by naloxone pretreatment
Cold-restraint stress for 3 h markedly induced gastric mucosal damage together with severe hemorrhage in the stomach. Pretreatment with morphine at doses of 2 or 8 mg/kg dose-dependently and significantly reduced the severity of mucosal damage (Fig. 1A). Stress significantly also increased the mucosal myeloperoxidase activity (Table 1), and morphine pretreatment partially reversed such action (Table 1). The lesion size was similar at 24 h later after a 3-h stress (immediately after a 3-h
Discussion
In this study, the antiulcer effect of morphine pretreatment was confirmed and it was found to be in a dose-dependent manner. Cold-restraint stress induced severe hemorrhagic lesions together with a mark increase in myeloperoxidase activity. This finding may indicate that stress ulceration is a neutrophil-dependent ulcerogenic process, because myeloperoxidase is a marker for neutrophil infiltration during inflammation in the stomach Chow et al., 1997, Tepperman et al., 1991. The increase of
Acknowledgements
We would like to thank the technical assistance of Miss Yu Y. Hang and Mr. C.P. Mok and also the financial support of the University of Hong Kong and Hong Kong Research Grant Council (HKU 7281/02M).
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