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)

Chronic abdominal pain is the most distressing symptom in patients with functional digestive disorders (FDD). IBS is the most common gastrointestinal disorder seen in primary care and gastroenterology practice. IBS is a functional bowel disorder in which abdominal pain is associated with defaecation or a change in bowel habit, with features of disordered defecation and with distension. The underlying pathophysiology of IBS is unknown but a chronic visceral hyperalgesia, in the absence of detectable organic disease, is implicated. The exact location of abnormality of visceral pain processing is not known. Theories of its etiology have range widely from the original view that the disease represents a primary disturbance of gut mucosa to emerging conception of the syndrome as emanating from a complex disordered interaction between the digestive and nervous systems. Several lines of evidence suggest a strong modulatory or etiologic role of the central nervous system in the pathophysiology of IBS. A major advance in the understanding of the central mechanisms of pain processing has evolved from application of functional imaging techniques, as represented by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). In humans, multiple components are involved in somato-visceral pain processings, including sensory-discriminative components, affective components, and cognitive components. Silverman et al, using PET, were the first to explore neural correlates of abdominal pain induced by rectal distension. If healthy subjects activated the ACC, the IBS patients did not while they presented an activation of the left PFC. These findings were consistent with an IBS model that includes both the exaggerated activation of a vigilance network (dorsolateral PFC) and a failure in pain inhibition network anterior cingulate cortex (ACC). In contrast, Mertz et al., using fMRI, observed that pain led to a greater activation of the ACC than did non-painful stimuli thus arguing for an up-regulation of afferent sensitivity to pain. Using fMRI, we also characterized cerebral loci activated by a rectal distension in healthy volunteers. The activation patterns presented a strong similarity with the central processing of somatic pain. In contrast, in a women predominant population of IBS patients, we did not observed any neuronal activation in locations activated in healthy volunteers (ACC, dorsolateral PFC) while a significant deactivation was observed in the IC and in the amygdala, a limbic structure with a role to assign emotional significance to a current experience related to anxiety and fear. Brain imaging techniques thus appear as useful tools to characterize normal and abnormal brain processing of visceral pain in patients with FDD. Reversal effects of chemical compounds targeting these abnormalities either at a peripheral or a central level should be of interest.
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PMID:Visceral sensitivity perturbation integration in the brain-gut axis in functional digestive disorders. 1507 47

In healthy subjects, the brain regions most consistently activated in visceral and somatic pain are the key regions in the central pain matrix,including the mid/anterior insula, subregions of the ACC, PFC, thalamus,and in some cases, pontine regions such as the dorsal pons and PAG. Functional neuroimaging studies have demonstrated evidence of altered regional brain activation responses during visceral and somatic stimuli in IBS that have been associated with perceptual differences. Although perceptual studies have shown increased sensitivity to rectosigmoid distension in IBS, most somatic pain studies have demonstrated normal or decreased sensitivity compared with controls; however, a recent study showed increased sensitivity to thermal heat. Altered brain responses in IBS,particularly to visceral stimuli, include activation of regions concerned with attentional processes and response selection, corticolimbic regions concerned with emotional and autonomic responses to stimuli, and subcortical regions receiving cortical projections from the latter and afferent input from the soma and viscera. Altered activations of these regions also may be present in the absence of a noxious visceral stimulus. Changes in rCBF of some of these regions have been associated with treatment response in IBS. With regard to differences in cortical processing of visceral versus somatic stimuli in IBS, there have been only two studies. Greater activations of the dorsal ACC, thalamus, and PFC have been shown with visceral stimuli compared with somatic stimuli in IBS. A plausible hypothesis for the observations from brain imaging studies is that IBS patients demonstrate a compromised activation of pain inhibition circuits including those of the cortico-pontine circuit but increased activation of limbic and paralimbic circuits that may be related to pain facilitation.
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PMID:Brain responses to visceral and somatic stimuli in irritable bowel syndrome: a central nervous system disorder? 1586 35