Purpose: Opioid analgesics have long been the primary treatment of postoperative pain. The use of these agents, however, is often associated with adverse effects on gastrointestinal motility including postoperative ileus. Recent efforts have focused on selective antagonists of the opioid-mu receptor. The purpose of this study is to examine the use of the herbal medicine Dai-Kenchu-to (DKT) as a potential treatment for opiate-induced slowing of intestinal transit in an isolated guinea-pig colon model of motility. We then investigated whether DKT could act synergistically with the non-selective opiate receptor antagonist, naloxone to promote propulsive motility.
Methods: Isolated segments of distal guinea-pig colon were mounted in a perfusion chamber and imaged with a digital video camera interfaced with a computer. Fecal pellets were placed into the lumen at the oral end of the colonic segment and the rates of motility over a 3-4 cm segment of colon were determined. In addition, intracellular recording were obtained from intact circular muscle. Inhibitory and excitatory junction potentials, evoked by stimulation above or below the recording site, respectively were analyzed.
Results: The addition of DAMGO (D-Ala2, N-Me-Phe4, Gly-ol5), a selective mu-receptor agonist, caused a concentration-dependent decrease in colon motility. Naloxone did not affect basal activity, but partially restored motility in the DAMGO treated preparations. DKT (1x10^-4-3x10^-4 g/ml) also reversed the inhibitory effect of DAMGO treated colon in a concentration dependent manner. At higher concentrations (1x10^-3-3x10^-3 g/ml), however, this effect was lost. Motility slowed even further when naloxone and DKT were combined, with noticeable disruptions in spatiotemporal patterns. Interestingly, when added alone, DKT caused a reversal of the peristaltic reflex resulting in propulsion of the pellet in an anal to oral direction. In electrophysiological studies, DKT inhibited both excitatory and inhibitory junction potentials.
Conclusions: DKT appears to be as effective as naloxone in restoring motility in DAMGO treated colon. These two agents, however, do not appear to have an addictive effect. When used on untreated colon segments, DKT appears to cause disruptions in the intrinsic reflex circuit of the gut by interfering with neuromuscular communication.