Peripheral effects of opioids in a model of intestinal inflammation in mice.

Abstract

The study evaluates the peripheral component of the antitransit effects of opioids during acute intestinal inflammation induced by the intragastric administration of croton oil (CO) in mice. Gastrointestinal transit was measured 3 h after CO or saline (SS) administration with a charcoal meal. In both groups, the effects of mixed (morphine, fentanyl, U-50488H) and peripherally acting (N-methylmorphine, PL017, ICI-204448) opioids and their antagonism by naloxone and naloxone methiodide were established. During inflammation, the potencies of morphine and N-methylmorphine increased 3 times, and those of fentanyl and PL017, 1.9 times. The effects were reversed by naloxone (0.1 mg/kg) and naloxone methiodide (0.3 mg/kg). No dose-response relationships could be elicited with U-50488H or ICI-204448, and their antitransit effects were analogous in SS- and CO-treated animals. These results show that during inflammation the enhanced antitransit effects of opioids are primarily mediated by interaction with opioid receptors located at peripheral sites. In addition, inflammation of the gut seems to induce a sensitization of mu-but not kappa-opioid receptors.