The Dual Effect of Cannabinoid Receptor-1 Deficiency on the Murine Postoperative Ileus

Abstract

IntroductionIntestinal inflammatory responses play a critical role in the pathogenesis of postoperative ileus (POI). As cannabinoid receptor-1 (CB1) is involved in inhibiting gastrointestinal (GI) motility and anti-inflammation, we aimed to explore its contribution to POI.MethodsExperimental POI was induced in adult female CB1-deficient (CB1–/–) mice and wild-type littermates (C57BL/6N) by standardized small bowel manipulation. Twenty-four hours after surgery, GI transit was assessed by charcoal transport. FITC avidin, F4/80, and myeloperoxidase immunohistochemistry techniques were used to evaluate the inflammatory response in the muscularis of ileum and colon. Expressions of p38MAPK and its phosphorylated form (pp38) in the intestine were determined. Plasma levels of proinflammatory cytokines and chemokines were measured by ELISA as well.ResultsPOI was characterized by decreased GI transit (p<0.01) and accompanied by a marked intestinal and systematic inflammatory response in wild-type and CB1–/– mice. Increased numbers of inflammatory cells, including macrophages, neutrophils, and mast cells were observed in the muscularis of ileum and colon (p<0.01, or p<0.05). Plasma levels of interleukin-6 (IL-6), cytokine-induced neutrophil chemoattractant-1 (CINC-1/KC), and monocyte chemoattractant protein-1 (MCP-1) were elevated (p<0.01, or p<0.05). Expression of p38 and pp38 increased in the intestine (p<0.01, or p<0.05). CB1–/– mice showed an increased inflammatory response during POI, especially the systemic inflammatory markers, such as IL-6, KC, CINC1, and pp38 expression were increased as compared to those in WT mice (p<0.05).ConclusionsIntestinal motility was inhibited during POI. In this condition, inhibition of motility did not seem to be altered by the absence of CB1 receptors, however, an increased inflammatory response was observed in CB1–/– mice. Hence, CB1 receptor activation rather than inhibition may reduce the inflammatory response in POI, which has a remote potential to relate into reduced inhibition of intestinal motility during POI.

Peritoneal Air Exposure Elicits an Intestinal Inflammation Resulting in Postoperative Ileus

“…The majority of the published reports suggest that POI is a transient gastrointestinal motility disorder involved in response to surgical stress [1, 5, 8, 26]. Enhancement of gastrointestinal motility will significantly improve POI [27, 28].…”

Irritable bowel syndrome: Emerging paradigm in pathophysiology

“…The endocannabinoid system, involved in motility [108] , sensation [109] , secretion [110,111] and inflammatory [112,113] functions in the gastrointestinal tract, has been proposed as a mechanism in the development of IBS. The endocannabinoid anandamide is inactivated by the fatty acid amide hydrolase (FAAH), and single nucleotide polymorphisms (SNPs) in the FAAH gene (C385A) have been associated with accelerated colonic transit time in D-IBS [108] .…”

Anti-inflammatory Effect of Ginsenoside Rb1 Contributes to the Recovery of Gastrointestinal Motility in the Rat Model of Postoperative Ileus

“…In the previous study, charcoal transport is commonly used as an objective measurement to assess gastrointestinal motility in animal research. 23,30,35,36) These studies demonstrate that POI is associated with decreased gastrointestinal transit assessed by charcoal transport. In the present study, we also employed charcoal transport to determine the gastrointestinal motility, and further investigate the improvement effect of GRb1 on POI.…”

“…Therefore, at 24 h after surgery, all rats in the 6 groups were selected to assess gastrointestinal motility by charcoal transport as described in the previous study. 30) Briefly, rats were administered with a black marker (10% charcoal suspension in 10% gum arabic, 10 mL/kg body weight) by gavage. Twenty minutes later, rats were fully anesthetized by subcutaneous injection of 2% pentobarbital sodium (3.5 mL/kg).…”