The aim of the present study was to examine the sensitivity of mesenteric afferents supplying the rat small intestine to
mu-opioid receptor ligands. Mesenteric afferent discharge was recorded electrophysiologically in response to [D-ALA2, N-Me-Phe4, Gly5-ol]-
enkephalin (
DAMGO; 100 mug kg(-1) i.v.), before and
after treatment with the
mu-receptor antagonist
alvimopan (1 mg kg(-1) i.v.).
DAMGO markedly stimulated whole nerve mesenteric afferent discharge (P < 0.05), an effect completely blocked by
alvimopan. The response of mesenteric afferents to
2-methyl-5-hydroxytryptamine (30 microg kg(-1) i.v.),
bradykinin (0.1-1 microg kg(-1) i.a.) and both low- and high-threshold distension (0-60 mmHg) was unaffected by
alvimopan. In chronically vagotomized animals, the low-threshold response to distension was attenuated while the remaining high-threshold response was unaffected by
alvimopan. In conclusion, mesenteric afferent fibres are markedly stimulated by
mu-opioid receptor agonists, an effect blocked by
alvimopan, which may contribute to the gastrointestinal reflex and behavioural responses to
opiate treatment or abuse. However,
alvimopan did not influence the normal sensitivity of intestinal afferents to chemical and mechanical stimuli that activate different subpopulations of vagal and spinal afferents. Thus,
alvimopan may be useful for the treatment of gastrointestinal sequelae following
opiate treatment for postoperative or
chronic pain.