MODULATION BY OPIOIDS AND BY AFFERENT SENSORY NEURONS OF PROSTANOID PROTECTION OF THE RAT GASTRIC-MUCOSA

1 Pretreatment with capsaicin, to deplete sensory neuropeptides from primary afferent neurones or the administration of morphine (9 mg kg-1, i.v.), which can inhibit neuropeptide release, augmented gastric mucosal injury induced by a 5 min challenge with intragastric ethanol in the rat, as assessed by macroscopic and histological evaluation. 2 Morphine administration substantially attenuated the protective actions of the prostaglandin analogue 16,16 dimethyl prostaglandin E2 (dm PGE2; 0.5-20-mu-g kg-1, p.o.) against ethanol-induced damage. This reduced degree of protection by dmPGE2 was not however, the consequence of the enhanced level of damage. 3 These actions of morphine in reducing prostaglandin protection against mucosal injury were abolished by pretreatment (5 min) with naloxone (1 mg kg-1, i.v.) or the peripherally acting opioid antagonist, N-methyl nalorphine (6 mg kg-1, i.v.). 4 Capsaicin pretreatment (2 weeks before study), likewise attenuated the protective actions of dmPGE2, although to a lesser degree than did morphine. 5 These findings, thus implicate the involvement of capsaicin- and opioid-sensitive afferent neurones in the processes by which exogenous prostanoids can protect the gastric mucosa from damage.