Pharmacological factors
The most commonly used drug for analgesia and anaesthesia is morphine, which is a central and peripheral \(\mu\) receptor agonist (De Winter et al., 1997c). This central and peripheral action contributes to prolongation of the POI, but gastrointestinal receptors have a predominant role in inhibiting postoperative gut motility (figure 1). Morphine and other opioid analgesics inhibit the release of acetylcholine from the mesenteric plexus, thereby increasing colonic muscle tone and reducing propulsive activity in the gastrointestinal tract (Schang et al., 1986; Delaney, 2004). There are several types of opioid receptors, the three main ones being μ, δ, and κ receptors, with each class also having several subtypes (Shahbazian et al., 2002). Opioid receptors are stimulated endogenously and exogenously (Gonenne et al., 2005; Becker and Blum, 2009). Exogenous opioids agonists such as such as morphine and codeine act primarily at μ-receptors which are present in the central and peripheral nervous system (Thomas, 2008). The μ-receptors of the enteric system are the main vectors for the effects on the gastrointestinal tract. The first level of action of opioids is inhibition of enteric nervous activity with inhibition of substance P, nitric oxide and acetylcholine secretion (Kowalski, 1998). This inhibits propulsive motor activity and leads to symptoms of the functional signs of ileus (digestive distension, inhibition of gastric emptying, etc.) (Ferraz et al., 1995). Previous studies on primate and clinical physiology investigating colonic myoelectrical activity have shown that, at a morphine dose range of 50 to 200 ug/l, there was an increase in the frequency of random, non-propagating bursts and contraction. Inhibition of colonic myoelectric activity and contraction were observed at higher doses (Frantzides et al., 1992; Ferraz et al., 1995). In addition, opioids are inducible nitric oxide synthase (iNOS) inducers, and the use of naloxone (mu-receptor antagonist) in murine models decreases NO production by resident macrophages (Kowalski, 1998).