Regulative effect of anandamide-mediated cannabinoid receptor in rats with visceral hypersensitivity / 解放军医学杂志

ABSTRACT

Objective To investigate the role of anandamide(ANA)-mediated cannabinoid receptor 1(CB1) on the acquisition of visceral hypersensitivity in rats, and explore its underlying mechanism. Methods The visceral hypersensitivity non-noxious/noxious colorectal distension (NNCRD/NCRD) model of rat was reproduced by ovalbumin (OVA) sensitization combined with NNCRD/NCRD. Fifty-four rats were randomly divided into control group (n=7), saline+CRD group (n=7), OVA+CRD+dimethyl sulfoxide (DMSO) group (n=8), OVA+CRD+different concentrations of ANA (0.5, 5.0, 10.0mg/kg) groups (8 each), and OVA+CRD+ANA+AM251 group (n=8). The expression and quantitative assessment of CB1 were monitored by immunoflurorescence and laser scanning confocal analysis. The visceral sensitivity was evaluated by the area under curve (AUC) of myoelectrical activity of abdominal wall muscle. Results By NCRD at 80mmHg, the density of CB1 immunofluorescence intensity was significantly higher in L4-L6 of the spinal cord of the rats in saline+CRD group compared with that in control group (P0.05). By NCRD at 80mmHg, the VMR-AUC increased obviously in OVA+CRD+DMSO group as compared with that of saline+CRD group, but it decreased significantly in OVA+CRD+high concentration ANA group (P<0.05). When AM251 was intravenously given, VMR-AUC increased significantly in OVA+CRD+ANA+AM251 group compared with that in OVA+CRD+different concentrations of ANA groups (P<0.05). Conclusions Intravenous administration of ANA may mitigate the visceral nociception induced by basic OVA-sensitization combined with NCRD stimulation in CB1-mediated manner. It indicated that anandamide-mediated CB1 cannabinoid receptor may regulate the development and maintenance of visceral hypersensitivity.