Influence of trimebutine on inflammation- and stress-induced hyperalgesia to rectal distension in rats

The effects of trimebutine and its major metabolite, N-desmethyltrimebutine on inflammation- and stress-induced rectal hyperalgesia have been evaluate d in rats fitted with electrodes implanted in the longitudinal striated mus cle of the abdomen. Intermittent rectal distension was performed before and 3 days after induct ion of rectal inflammation by local infusion of trinitrobenzenesulphonic ac id (in ethanol). Stress consisted of 2 h partial restraint and rectal diste nsion was performed before and 30 min after the end of the partial restrain t session. The animals were treated intraperitoneally with trimebutine or d esmethyltrimebutine (5, 10 or 20 mg kg(-1)) or vehicle 15 min before rectal distension. Naloxone (1 mg kg(-1)) or saline was injected subcutaneously b efore trimebutine and desmethyltrimebutine. Before treatment trimebutine at the highest dose (20 mg kg(-1)) reduced the abdominal response to rectal d istension for the highest volume of distension (1.6 mL) whereas desmethyltr imebutine was inactive. After rectocolitis the abdominal response to rectal distension was enhanced and trimebutine at 5 mg kg(-1) reduced and at 10 m g kg(-1) suppressed inflammation-induced hyperalgesia, an effect reversed b y naloxone. Desmethyltrimebutine was inactive. Stress-induced hypersensitiv ity was attenuated or suppressed, or both, by trimebutine and desmethyltrim ebutine at doses of 5, 10 or 20 mg kg(-1) greater efficacy was observed for desmethyltrimebutine and the effects were not reversed by naloxone, It was concluded that trimebutine and desmethyltrimebutine are active again st inflammation- and stress-induced rectal hyperalgesia but act differently . The effect of trimebutine on inflammation-induced hyperalgesia is mediate d through opioid receptors.