Abdominal surgery induces μ opioid receptor endocytosis in enteric neurons of the guinea-pig ileum

Abstract

Immunohistochemistry and confocal microscopy were used to investigate μ opioid receptor (μOR) internalization in enteric neurons of the guinea-pig ileum following abdominal surgery. The following surgical procedures were performed under halothane or isofluorane anesthesia: a) midline abdominal skin incision, b) laparotomy or c) laparotomy with intestinal manipulation. Gastrointestinal transit was evaluated by using a non-absorbable marker and measuring fecal pellet output. In neurons from normal and control (anesthesia alone) animals, μOR was predominantly at the cell surface. μOR endocytosis following skin incision was not significantly different from controls (21.2±3.5% vs. 13.7±2.1%, mean±S.E.M.), whereas it was significantly increased by laparotomy (46.5±6.1%; P<0.01 vs. controls) or laparotomy plus intestinal manipulation (40.5±6.1%; P<0.01 vs. controls) 30 min following surgery compared with controls. μOR endocytosis remained elevated at 4 h (38.6±1.2%; P<0.01 vs. controls), whereas it was similar to controls at 6 and 12 h (17.5±5.8% and 11.2±3.0%). μOR endocytosis occurred in cholinergic and nitrergic neurons. Gastrointestinal transit was significantly delayed by laparotomy or laparotomy plus intestinal manipulation (12.8±1.2 and 13.8±0.6 h vs. 7.0±0.5 in controls; P<0.01), but was not significantly changed by skin incision (8.2±0.6 h). The findings of the present study support the concept that the noxious stimulation caused by abdominal surgery induces release of endogenous opioids thus resulting in μOR endocytosis in neurochemically distinct enteric neurons. μOR internalization can serve as indirect evidence of opioid release and as a means to visualize neuronal pathways activated by opioids.