Fluoroscopic Characterization of Colonic Dysmotility Associated to Opioid and Cannabinoid Agonists in Conscious Rats

Abstract

Background/Aims Gastrointestinal adverse effects have a major impact on health and quality of life in analgesics users. Non-invasive methods to study gastrointestinal motility are of high interest. Fluoroscopy has been previously used to study gastrointestinal motility in small experimental animals, but they were generally anesthetized and anesthesia itself may alter motility. In this study, our aim is to determine, in conscious rats, the effect of increasing doses of 2 opioid (morphine and loperamide) and 1 cannabinoid (WIN 55,212-2) agonists on colonic motility using fluoroscopic recordings and spatio-temporal maps. Methods Male Wistar rats received barium sulfate intragastrically, 20-22 hours before fluoroscopy, so that stained fecal pellets could be seen at the time of recording. Animals received an intraperitoneal administration of morphine, loperamide, or WIN 55,212-2 (at 0.1, 1, 5, or 10 mg/kg) or their corresponding vehicles (saline, Cremophor, and Tocrisolve, respectively), 30 minutes before fluoroscopy. Rats were conscious and placed within movement-restrainers for the length of fluoroscopic recordings (120 seconds). Spatio-temporal maps were built, and different parameters were analyzed from the fluoroscopic recordings in a blinded fashion to evaluate colonic propulsion of endogenous fecal pellets. Results The analgesic drugs inhibited propulsion of endogenous fecal pellets in a dose-dependent manner. Conclusions Fluoroscopy allows studying colonic propulsion of endogenous fecal pellets in conscious rats. Our method may be applied to the noninvasive study of the effect of different drug treatments and pathologies.

Effects of two different acute and subchronic stressors on gastrointestinal transit in the rat: A radiographic analysis

“…Possibly, small differences could be better observed by using metabolic cages (although this would introduce additional stress), or delaying the moment of stress application and visualization of the effects through X-rays or, even better, fluoroscopy. 38 When the stressors were applied for 4 consecutive days, we found that the density of content in the stomach remained higher than in the control group; thus, we did not see a clear habituation to the stressful stimuli. The effect of repeated stressful stimuli on stomach emptying is somewhat contradictory in the literature; that is, psychological stress induced by the communicating box decreased gastric emptying when applied chronically, 39 gastric emptying was accelerated when rats were kept in cages filled with 2 cm of water for 5 consecutive days, 40 and habituation to partial restraint stress was found after 5 days of this same stressful stimulus, 2,41 adaptation was not seen after 5 consecutive days of CRF administration.…”

The Enteric Glia and Its Modulation by the Endocannabinoid System, a New Target for Cannabinoid-Based Nutraceuticals?

“…The ECS is also involved in the control of GI peristalsis and transit [ 14 ]. In particular, CB1 receptors were pointed out as involved in the inhibitory effect of cannabinoids, both, under control [ 167 , 168 , 169 , 170 , 171 ] and under inflammatory conditions [ 172 ]. IBS, or chemotherapy-induced dysmotility are associated with alterations in CB1 and CB2 receptors expression/activity, levels of ECBs or ECB biosynthesis/degradation.…”