Acute colitis induction by oil of mustard results in later development of an IBS-like accelerated upper GI transit in mice

Abstract

Oil of mustard (OM) is a potent neuronal activator that promotes allodynia and hyperalgesia within minutes of application. In this study, OM was used to induce an acute colitis. We also investigated whether intracolonic OM-induced inflammation alters gastrointestinal (GI) function over a longer time frame as a model of postinflammatory irritable bowel syndrome (PI-IBS). Mice given a single administration of 0.5% OM developed a severe colitis that peaked at day 3, was reduced at day 7, and was absent by day 14. At the peak response, there was body weight loss, colon shrinkage, thickening and weight increases, distension of the proximal colon, and diarrhea. Macroscopic inspection of the distal colon revealed a discontinuous pattern of inflammatory damage and occasional transmural ulceration. Histological examination showed loss of epithelium, an inflammatory infiltrate, destruction of mucosal architecture, edema, and loss of circular smooth muscle architecture. OM administration increased transit of a carmine dye bolus from 58% of the total length of the upper GI tract in untreated age-matched controls to as high as 74% when tested at day 28 post-OM. Mice in the latter group demonstrated a significantly more sensitive response to inhibition of upper GI transit by the mu-opioid receptor agonist loperamide compared with normal mice. OM induces a rapid, acute, and transient colitis and, in the longer term, functional changes in motility that are observed when there is no gross inflammation and thereby is a model of functional bowel disorders that mimic aspects of PI-IBS in humans.

The Effects of an Extract ofAtractylodes JaponicaRhizome, SKI3246 on Gastrointestinal Motility in Guinea Pigs

“…1 Meanwhile, it has been known that MO displays proinflammatory activity mainly via inducing plasma extravasation, which is principally due to the release of substance P and to NK1 receptor activation. [7][8][9][10] These differences in mechanism between the 2 agents may explain in part the lack of GI motility response to SKI3246 in the MO-induced model in this study.…”

“…MO, allyl isothiocyanate, the predominant aromatic constituent of mustard, horseradish, and wasabi, is a direct stimulant of small nerve fibers and a potent acute inflammatory irritant. 7 Although the GI response to MO in guinea pig is not well-documented, the intra-colonic administration of MO in mice results in acute colitis, which may progress to an IBS-like acceleration of upper GI transit. 7 In our guinea pig Figure 4.…”

“…7 Although the GI response to MO in guinea pig is not well-documented, the intra-colonic administration of MO in mice results in acute colitis, which may progress to an IBS-like acceleration of upper GI transit. 7 In our guinea pig Figure 4. Effect of SKI3246 on lower gastrointestinal motility in thyrotropin-releasing hormone (TRH) pretreated guinea pigs.…”

Visceral and Somatic Hypersensitivity in TNBS-Induced Colitis in Rats

“…Mahgoub et al [41] used intracolonic 3% ascetic acid which produced severe colitis 24 hours after administration. Kimball et al [42] used mustard oil that caused a peak inflammation at day 3 and was resolved by day 7. The Natah group found that a quantitative analysis of the endothelial barrier antigen (EBA) after TNBS induced colitis resulted in occluding expression in the frontal cortex.…”

Novel insights which may translate into treatments for irritable bowel syndrome

“…Kimball et al evaluated the effect of selective cannabinoid receptor agonists in a mouse model of accelerated upper gastrointestinal transit resembling post-inflammatory IBS (PI-IBS) (Kimball et al, 2010). The experimental model is generated by intracolonic administration of mustard oil, which induce transient colitis and, in the longer term (i.e., 28 days after mustard oil) a functional increase in gastrointestinal transit that is observed when there is no inflammation (Kimball et al, 2005). It was found that both cannabinoid receptor subtypes were up-regulated in the small intestine, an effect closely associated to increased efficacy of both CB 1 and CB 2 receptor agonists in normalizing the accelerated transit (Kimball et al, 2010).…”