Involvement of Hypothalamo-Hypophyseal-Adrenocortical System Hormones in Gastroprotection in Rats on Sensitization and Desensitization of Capsaicin-Sensitive Afferent Neurons

The aims of the present work were: a) to study the contribution of glucocorticoid hormones to gastroprotection induced by sensitization of capsaicin-sensitive afferent neurons (CSN); b) to study the gastroprotective effect of corticotropin-releasing factor (CRF) in conditions of desensitization of CSN and the possible involvement of corticosterone in this effect. Experiments were run using male Sprague–Dawley rats weighing 260–300 g. Ulcerogenic stimuli consisted of immobilization at 10°C (3 h) or administration of indomethacin at a dose of 35 mg/kg. Sensitization of CSN was by administration of capsaicin at doses of 1 and 10 mg/kg 1 h before presentation of ulcerogenic stimuli and desensitization was by administration of capsaicin to a total neurotoxic dose of 100 mg/kg (20 + 30 + 50) on three sequential days two weeks before experiments started. CRF was given i.p. at a dose of 2.5 mg/kg 30 min before administration of indomethacin to rats with desensitization of CSN. Studies of the involvement of corticosterone in the gastroprotective effects used its synthesis inhibitor metyrapone at a dose of 30 mg/kg. Capsaicin given at doses of 1 and 10 mg/kg induced gastroprotective effects in both ulcerogenesis models. Administration of metyrapone 30 min before capsaicin prevented the gastroprotective effect of CSN sensitization induced by administration of capsaicin at a dose of 1 mg/kg, but has no effect on the gastroprotective effect of capsaicin at a dose of 10 mg/kg. Administration of CRF induced a gastroprotective effect not only in control rats, but also in animals with desensitization of CSN. The results of experiments with metyrapone provided evidence that the gastroprotective effect of CRF seen here in rats with desensitization of CSN was at least partially mediated by corticosterone. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.