M Goebel

Somatic comorbidities of irritable bowel syndrome: a systematic analysis.

OBJECTIVEnA large number of irritable bowel syndrome (IBS) patients are additionally afflicted with other somatic intestinal and/or extraintestinal comorbidities. The occurrence of one or more comorbidities is correlated with enhanced medical help seeking, worse prognosis, and higher rates of anxiety and depression-all resulting in a reduced quality of life. The aims of this study were, firstly, to review the literature on comorbidities of IBS and to assess gastrointestinal and extraintestinal comorbidities, and, secondly, to evaluate explanatory hypotheses and possible common pathophysiological mechanisms.nnnMETHODSnWe systematically reviewed the scientific literature in the past 25 years, as cited in MEDLINE.nnnRESULTSnIBS patients present with a twofold increase in somatic comorbidities compared to controls, possibly caused by common pathophysiological mechanisms. Nevertheless, to date, there has been no convincing evidence for a consolidated underlying pathophysiology or somatization. Gastrointestinal disorders, such as functional dyspepsia, gastroesophageal reflux disease, functional constipation, and anal incontinence, occur in almost half of the patients. In a broad variety of extraintestinal comorbidities, fibromyalgia, chronic fatigue syndrome, and chronic pelvic pain are best documented and appear in up to 65%.nnnCONCLUSIONnThe knowledge and structured assessment of comorbid somatic symptoms might allow to identify subgroups of IBS patients with special characteristics and lead to adaptation of the therapeutic concept.

Peripheral injection of ghrelin induces Fos expression in the dorsomedial hypothalamic nucleus in rats.

Peripheral ghrelin has been shown to act as a gut-brain peptide exerting a potent orexigenic effect on food intake. The dorsomedial nucleus of the hypothalamus (DMH) is innervated by projections from other brain areas being part of the network of nuclei controlling energy homeostasis, among others NPY/AgRP-positive fibers arising from the arcuate nucleus (ARC). The aim of the study was to determine if peripherally administered ghrelin affects neuronal activity in the DMH, as assessed by Fos expression. The number of Fos positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), ARC, ventromedial hypothalamic nucleus (VMH), nucleus of the solitary tract (NTS) and in the area postrema (AP) in non-fasted Sprague-Dawley rats in response to intraperitoneally (ip) injected ghrelin (3 nmol/rat) or vehicle (0.15 M NaCl). Peripheral ghrelin induced a significant increase in the number of Fos-ir positive neurons/section compared with vehicle in the ARC (mean+/-SEM: 49+/-2 vs. 23+/-2 neurons/section, p=0.001), PVN (69+/-5 vs. 34+/-3, p=0.001), and DMH (142+/-5 vs. 83+/-5, p<0.001). Fos-ir positive neurons were mainly localized within the ventral part of the DMH. No change in Fos expression was observed in the VMH (53+/-8 vs. 48+/-6, p=0.581), NTS (42+/-2 vs. 40+/-3, p=0.603), and in the AP (7+/-1 vs. 5+/-1, p=0.096). Additional double-labelling with anti-Fos and anti-AgRP revealed that Fos positive neurons in the DMH were encircled by a network of AgRP-ir positive fibers. These data indicate that peripheral ghrelin activates DMH neurons and that NPY-/AgRP-positive fibers may be involved in the response.