Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychological stress experienced in early life plays an important role in the development of visceral hyperalgesia in irritable bowel syndrome (IBS). Neonatal maternal separation has been shown to trigger a long-term alternation in stress-induced responses to visceral nociceptive stimuli in rats. The aim of the present study was to show a direct evidence of stress-induced alteration in central neuronal responses to colorectal distention (CRD) in rats by a quantitative study of c-fos expression in relevant brain structures. Male Wistar rat pups were subjected to 180-min daily neonatal maternal separation (NMS) for 13 consecutive days (from PND 2 to PND 14). The expression of c-fos was examined by using immunohistochemistry. Increased c-fos expression was observed, for the first time, in the cingulate cortex (3-fold) in NMS rats in comparison with the control group at basal condition. At noxious CRD (80 mm Hg), c-fos expression was induced in the supraspinal centers and in both the superficial (laminae I-II) and the deeper laminae (laminae V-VI and X) of the spinal cord in rats. Significantly more Fos-IR nuclei were found in the laminae I and II, and laminae V-VI of the lumbarsacral spinal cord, the paraventricular thalamic nucleus, the cingulate cortex, the amygdaloid central nucleus in NMS rats, but not in the solitary tract, the central medial thalamic nucleus, the ventromedial hypothalamic nucleus, and the periaquaductal gray. The present results indicate that NMS has sensitized the cingulate cortex and upregulated the activity of the ascending pathway at spinal level as well as the thalamo-cortico-amydala pathway to CRD. The upregulation and sensitization of these pathways may be responsible for the development of visceral hypersensitivity in IBS.
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PMID:Neonatal maternal separation enhances central sensitivity to noxious colorectal distention in rat. 1743 64

Early-life stress is a risk factor for irritable bowel syndrome (IBS), a common and debilitating functional gastrointestinal disorder that is often co-morbid with stress-related psychiatric disorders. In the rat, maternal separation (MS) stress has been shown to induce visceral hypersensitivity in adulthood and thus has become a useful model of IBS. However, development of mouse models of maternal separation has been difficult. Given the advent of transgenic mouse technology, such models would be useful to further our understanding of the pathophysiology of IBS and to develop new pharmacological treatments. Thus, the present study aimed to develop a mouse model of MS stress-induced visceral hyperalgesia as measured using manometric recordings of colorectal distension (CRD). Moreover, since the GABA(B) receptor has been reported to play a role in pain processes, we also assessed its role in visceral nociception using novel GABA(B(1b)) receptor subunit knockout mice. CRD was performed in adult male wildtype and GABA(B(1b)) receptor knockout mice that had undergone unpredictable MS combined with unpredictable maternal stress (MSUS) from postnatal day 1 through 14 (PND 1-14). MSUS induced visceral hypersensitivity in both wildtype and GABA(B(1b)) receptor knockout mice when compared with non-stressed mice. Wildtype and GABA(B(1b)) receptor knockout mice did not differ in baseline or stress-induced visceral sensitivity. To the best of our knowledge, this is the first study to show that early-life stress induces visceral hypersensitivity in a mouse model. These findings may provide a novel mouse model of visceral hypersensitivity which may aid our understanding of its underlying mechanisms in future studies.
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PMID:Early-life stress induces visceral hypersensitivity in mice. 2232 88