Opioids, the Enteric Nervous System, and Postoperative Ileus

Postoperative ileus, which is characterized by quiescence of the intestinal musculature, reflects the operation of a neural program in the enteric nervous system (ENS) in which the synapses that form the propulsive motor circuits are “locked” into an inactive state. In the inactive state, a component of the inhibitory motor innervation of the musculature remains active, and as a consequence, responsiveness of the muscle to electrical signals from pacemaker cells called interstitial cells of Cajal is suppressed. Physiological ileus is the normal absence of motility that occurs for varying lengths of time in different digestive states. Physiological motor quiescence becomes pathological when the synapses in the neural microcircuits for the motor programs in the ENS program library are rendered inoperative for abnormally long periods. In this state of paralytic ileus, the basic circuits are “locked” in an inactive state, while unremitting activity of inhibitory motor neurons continuously suppresses autogenic muscular activity. Release and actions of endogenous opioid peptides within the ENS inactivate the synaptic microcircuits and might account for the accompanying paralytic ileus. This hypothesis is based in part on the known actions of opioid peptides and opiates on the cellular neurophysiology of enteric neurons. 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-all of which are related to suppression of neuronal excitability and synaptic transmission in the ENS.