Peripheral opiate action on afferent fibres supplying the rat intestine

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Abstract
The aim of the present study was to examine the sensitivity of mesenteric afferents supplying the rat small intestine to µ‐opioid receptor ligands. Mesenteric afferent discharge was recorded electrophysiologically in response to [D‐ALA2, N‐Me‐Phe4, Gly5‐ol]‐enkephalin (DAMGO; 100 µg kg−1 i.v.), before and after treatment with the µ‐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 µg kg−1 i.v.), bradykinin (0.1–1 µg 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 µ‐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.