Peripheral opiate action on afferent fibres supplying the rat intestine

Abstract

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.

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

“…Similarly, activation of peripheral opioid -, ␦-, and -receptors increases the discharge activity of testis-spermatic sensory nerves of dogs (30). Moreover, opioid receptor ligands excite rat mesenteric afferent nerve nerves and mouse DRG neurons, responses that can be eliminated by opioid receptor antagonism (25,55). In contrast, other studies (48,54,58) have shown that activation of opioid receptors on pelvic and gastric vagal afferent nerves modulates visceral pain.…”

“…Opioid -, ␦-, and -receptors in the peripheral nervous system may play an important physiological role, although virtually all previous studies have involved the pharmacological application of opioid agonists (59). Furthermore, variable somatic and vagal sensory neural responses to the activation of opioid receptors have been reported (2,9,10,25,30,52). In this regard, the -receptor agonist [D-Ala 2 , N-MePhe 4 , Glyol]-enkephalin (DAMGO) directly excites rat small intestinal afferent nerves (11).…”

“…Anatomical studies (13,24,42,59) have found all three opioid receptors on sensory neurons in the dorsal root ganglia (DRG). However, the responses of peripheral somatic and visceral sensory nerves to exogenous opioids are controversial (2,9,10,25,30,52). Some investigators (25,55) have observed that opioid receptor agonists markedly excite rat mesenteric afferent fibers and mouse sensory DRG neurons and that these opioid actions are eliminated by blockade of opioid receptors.…”

“…However, the responses of peripheral somatic and visceral sensory nerves to exogenous opioids are controversial (2,9,10,25,30,52). Some investigators (25,55) have observed that opioid receptor agonists markedly excite rat mesenteric afferent fibers and mouse sensory DRG neurons and that these opioid actions are eliminated by blockade of opioid receptors. In contrast, Wenk and colleagues (68) demonstrated that opioids inhibit the majority of somatic A␦-and C-fiber nociceptors innervating inflamed skin.…”

The influence of opioids on gastric function: experimental and clinical studies

“…Higher centers involved in the regulation of gastrointestinal motility also express MORs (46,69,70). Opioid receptors are also present on afferent vagal nerve endings projecting to the NTS (47,71,72).…”