Function of opioids in the enteric nervous system

Abstract

Alterations in gastrointestinal motility and secretion underlie the constipating action of therapeutically administered opiates. The prototype opiate is morphine, which acts to delay gastric emptying and intestinal transit, to suppress intestinal secretion of water and electrolytes and to suppress transport of bile into the duodenum. The effects of opiates, synthetic opioids and endogenously released opioid peptides on these organ-level gastrointestinal functions reflect actions on electrical and synaptic behaviour of neurones in the enteric nervous system. Adverse effects and positive therapeutic effects of administration of opioid-receptor-blocking drugs on the digestive tract must be understood in the context of the neurophysiology of the enteric nervous system and mechanisms of neural control of gastrointestinal smooth muscle, secretory glands and blood-lymphatic vasculature. We review here the integrated systems of physiology and cellular neurobiology that are basic to understanding the actions of opioid agonists and antagonists in the digestive tract.

Enteric Nervous System: Neuropathic Gastrointestinal Motility

“…Opiates and opioids induce non-propulsive intestinal motility and suppress mucosal secretion of H 2 O and electrolytes, each of which reflects suppression of excitability in ENS motor neurons [22][23][24]. Morphine, the classical opiate, slows intestinal transit by elevating contractile tone in the intestinal circular muscle coat in animal models and humans.…”

“…Contractile behavior, associated with opiates or opioids, reflects depressed excitability of inhibitory musculomotor neurons in the ENS and release of the autogenic circular muscle coat from inhibitory neural suppression [23,27]. Moreover, presynaptic inhibitory action of morphine suppresses release of acetylcholine at the thousands of nicotinic synapses in the ENS microcircuitry [22,28].…”

The Impact of Opioid Treatment on Regional Gastrointestinal Transit

“…The exclusion criteria were (1) known allergy towards opioids, (2) participation in any other studies within 14 days of enrolment, (3) planned medical/surgical treatment within the study duration, (4) a need to operate heavy machinery or motor vehicles during the study, (5) any previous or current drug abuse, (6) non-removable piercings or metal implants, (7) daily alcohol or nicotine consumption, (8) any known disease that may influence the results, and (9) the use of prescribed medicine and/or herbal medicine.…”

“…1,2 They result from binding of exogenous opioids to opioid-receptors in the enteric nervous system, consequently disturbing normal GI function and manifesting in symptoms including gastroesophageal reflux, vomiting, bloating, abdominal pain, anorexia, hard stools, constipation, and incomplete evacuation. 3 Severe adverse effects are often the reason patients discontinue opioid treatment, which naturally results in inadequate pain management.…”

Epidural analgesia and gastrointestinal motility after open abdominal surgery-a review

“…Morphine is known to delay gastric emptying and intestinal transit, to suppress the intestinal secretion of water and electrolytes, and to inhibit the transport of bile into the duodenum (Wood, 2004); however, epidural morphine can shorten postoperative ileus (Morimoto et al, 1995;Delaney, 2004). Low doses of morphine have been reported to induce premature phase III-like activity in dogs (Konturek et al, 1980, Sarna et al, 1984Lewis et al, 1999) and humans (Waterfall, 1983), whereas a supramaximal dose of morphine did not initiate premature phase III contractions and alter the migration of migrating myoelectric complexes (Sarna et al, 1982).…”