Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
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Neurogastroenterol. Motil. · Jan 2016
ReviewEmerging treatments in neurogastroenterology: eluxadoline - a new therapeutic option for diarrhea-predominant IBS.
Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder worldwide. The global prevalence of IBS is estimated to be as high as 15%. For many patients, IBS is a chronic disorder which can significantly reduce quality of life. Just as important as the effects on any one individual, IBS also places a significant impact on the population as a whole with its negative effects on the health care system. Irritable bowel syndrome is categorized into one of three main categories: IBS with diarrhea, IBS with constipation, and IBS with mixed bowel habits. Patients with diarrhea-predominant IBS (IBS-D) comprise a substantial proportion of the overall IBS population. A number of therapeutic options exist to treat the symptoms of abdominal pain, bloating, diarrhea, and fecal urgency, including non-pharmacologic therapies such as dietary changes and probiotics, or pharmacologic therapies such as loperamide and alosetron. However, many patients have persistent symptoms despite these therapies. This unmet need led to the development of eluxadoline, a mu-opioid receptor agonist/delta-opioid receptor antagonist/kappa-receptor agonist. Approved by the FDA in May 2015, this medication shows promise in the treatment of diarrhea-predominant IBS for both men and women. ⋯ This monograph will briefly review the impact of IBS, discuss current treatments for IBS-D, and then focus on the pharmacology, clinical efficacy and safety of eluxadoline. Potential mechanisms related to rare events of acute pancreatitis or elevated liver tests will be discussed.
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Neurogastroenterol. Motil. · Jan 2016
Excessive coupling of the salience network with intrinsic neurocognitive brain networks during rectal distension in adolescents with irritable bowel syndrome: a preliminary report.
The neural network mechanisms underlying visceral hypersensitivity in irritable bowel syndrome (IBS) are incompletely understood. It has been proposed that an intrinsic salience network plays an important role in chronic pain and IBS symptoms. Using neuroimaging, we examined brain responses to rectal distension in adolescent IBS patients, focusing on determining the alteration of salience network integrity in IBS and its functional implications in current theoretical frameworks. We hypothesized that (i) brain responses to visceral stimulation in adolescents are similar to those in adults, and (ii) IBS is associated with an altered salience network interaction with other neurocognitive networks, particularly the default mode network (DMN) and executive control network (ECN), as predicted by the theoretical models. ⋯ Our study provided consistent evidence supporting the theoretical predictions of altered salience network functioning as a neuropathological mechanism of IBS symptoms.
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Neurogastroenterol. Motil. · Jan 2016
Altered brain responses in subjects with irritable bowel syndrome during cued and uncued pain expectation.
A majority of the subjects with irritable bowel syndrome (IBS) show increased behavioral and brain responses to expected and delivered aversive visceral stimuli during controlled rectal balloon distension, and during palpation of the sigmoid colon. We aimed to determine if altered brain responses to cued and uncued pain expectation are also seen in the context of a noxious somatic pain stimulus applied to the same dermatome as the sigmoid colon. ⋯ The observed greater engagement of cognitive and emotional brain networks in IBS subjects during contextual threat may reflect the propensity of IBS subjects to overestimate the likelihood and severity of future abdominal pain.
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Neurogastroenterol. Motil. · Jan 2016
Auricular vagal nerve stimulation ameliorates burn-induced gastric dysmotility via sympathetic-COX-2 pathways in rats.
Severe burn injury has been demonstrated to delay gastric emptying. The aim of this study was to investigate effects and cellular mechanisms of auricular electroacupuncture (AEA) at the acupoints innervated by the auricular branch of vagus nerve on burn-induced gastric dysmotility in rats. ⋯ Burn injury delays gastric emptying by up-regulating COX-2 attributed to sympathetic overactivity. AEA improves burn-induced delay in gastric emptying, possibly mediated via the sympathetic-COX-2 pathway.