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)

It is widely appreciated that visceral pain differs significantly from pain that arises from cutaneous structures. Visceral pain is difficult for both the patient and physician to localize because it is diffuse in character and is typically referred to cutaneous structures. Further, there are differences between acute, post-operative visceral pain and the altered sensations associated with the so-called functional bowel disorders (e.g. non-ulcer dyspepsia, non-cardiac chest pain and irritable bowel syndrome). A variety of considerations suggests that sensory inputs from the fiscera, like nociceptive inputs from the skin, can be sensitized. Accordingly, inputs from the viscera that are not typically perceived may give rise to discomfort and pain if either visceral afferent fibres are sensitized or central neurones undergo a change in excitability ('central sensitization') after persistent visceral input. The anatomy and potential mechanisms associated with visceral hyperalgesia will be considered as will new information about opioid modulation of visceral inputs to the spinal cord.
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PMID:Visceral nociception: consequences, modulation and the future. 764 39

Visceral pain is characterized by a subjectively painful perception located in the abdominal area. Distinct structural lesions or biochemical abnormalities which could serve as explanation for these painful sensations can be only detected in a proportion of patients. In the absence of precise causes for visceral pain, the symptoms are attributed to functional disorders. The two major single entities among functional disorders of the gut are functional dyspepsia and irritable bowel syndrome. Patients with functional dyspepsia characteristically localize the symptoms in the upper abdomen. Functional gastrointestinal disturbances which are localized in the lower abdomen are summarized as irritable bowel syndrome. Interestingly,both functional dyspepsia and irritable bowel syndrome may overlap.
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PMID:[Epidemiology and clinical phenomenology of visceral pain]. 1247 30

Visceral pain is the most common form of pain produced by disease and is thus of interest in the study of gastrointestinal (GI) complaints such as irritable bowel syndrome, in which sensory signals perceived as GI pain travel in extrinsic afferent neurones with cell bodies in the dorsal root ganglia (DRG). The DRG from which the primary spinal afferent innervation of the mouse descending colon arises are not well defined. This study has combined retrograde labelling and immunohistochemistry to identify and characterize these neurones. Small to medium-sized retrogradely labelled cell bodies were found in the DRG at levels T8-L1 and L6-S1. Calcitonin gene-related peptide (CGRP)- and P2X3-like immunoreactivity (LI) was seen in 81 and 32%, respectively, of retrogradely labelled cells, and 20% bound the Griffonia simplicifolia-derived isolectin IB4. CGRP-LI and IB4 were co-localized in 22% of retrogradely labelled cells, whilst P2X3-LI and IB4 were co-localized in 7% (vs 34% seen in the whole DRG population). Eighty-two per cent of retrogradely labelled cells exhibited vanilloid receptor 1-like immunoreactivity (VR1-LI). These data suggest that mouse colonic spinal primary afferent neurones are mostly peptidergic CGRP-containing, VR1-LI, C fibre afferents. In contrast to the general DRG population, a subset of neurones exist that are P2X3 receptor-LI but do not bind IB4.
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PMID:Characterization of the primary spinal afferent innervation of the mouse colon using retrograde labelling. 1476 11

Irritable bowel syndrome (IBS) is characterized by abdominal pain associated with disordered defecation, which may include urgency and altered stool frequency. Visceral pain syndromes, including IBS, may be effectively treated by a variety of therapies that modulate the interactions between the central and enteric nervous systems. Clinical observations and preliminary data suggest that antidepressants may be efficacious for the treatment of these syndromes. The tricyclic antidepressants (TCAs) have been utilized most extensively in this area, but there is a need for more rigorous efficacy data. Serotonin, an important neurotransmitter in both the central and enteric nervous systems, modifies both motility and sensation in the gut. Recognition of the importance of serotonin in digestive motility and sensation has sparked interest in the use of agents that modify serotonergic transmission in visceral pain syndromes. Pharmacological therapeutics that modulate the biological amines (serotonin, norepinephrine, dopamine and catecholamines) both peripherally and within the central nervous system may offer more effective therapies for these disorders. The selective serotonin reuptake inhibitors are commonly used in clinical practice, but more rigorous, controlled studies are needed to determine their effects beyond the treatment of psychiatric comorbidity. The newer generation antidepressants may provide additional insight into the pathophysiology of the brain-gut interactions and their relationship to functional bowel disorders, providing new therapeutic interventions.
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PMID:Antidepressants in the treatment of irritable bowel syndrome and visceral pain syndromes. 1529 70

Visceral pain processing is abnormal in a majority of irritable bowel syndrome (IBS) patients. Aberrant endogenous nociceptive modulation and anticipation are possible underlying mechanisms investigated in the current study. Twelve IBS patients and 12 matched healthy controls underwent brain fMRI scanning during the following randomised stimuli: sham and painful rectal distensions by barostat without and with simultaneous activation of endogenous descending nociceptive inhibition using ice water immersion of the foot for heterotopic stimulation. Heterotopic stimulation decreased rectal pain scores from 3.7+/-0.2 to 3.1+/-0.3 (mean+/-SE, scale 0-5) in controls (p<0.01), but not significantly in IBS. Controls differed from IBS patients in showing significantly greater activation bilaterally in the anterior insula, SII and putamen during rectal stimulation alone compared to rectal plus heterotopic stimulation. Greater activation during rectal plus heterotopic versus rectal stimulation was seen bilaterally in SI and the right superior temporal gyrus in controls and in the right inferior lobule and bilaterally in the superior temporal gyrus in IBS. Rectal pain scores were similarly low during sham stimulation in both groups, but brain activation patterns differed. In conclusion, IBS patients showed dysfunctional endogenous inhibition of pain and concomitant aberrant activation of brain areas involved in pain processing and integration. Anticipation of rectal pain was associated with different brain activation patterns in IBS involving multiple interoceptive, homeostatic, associative and emotional areas, even though pain scores were similar during sham distension. The aberrant activation of endogenous pain inhibition appears to involve circuitry relating to anticipation as well as pain processing itself.
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PMID:Cortical effects of anticipation and endogenous modulation of visceral pain assessed by functional brain MRI in irritable bowel syndrome patients and healthy controls. 1684 94

Defective colonic and gastric accommodations have been related to altered viscerosensitivity in irritable bowel syndrome and to functional dyspepsia, respectively. We assessed colonic accommodation in rats with impaired gastric accommodation to determine if altered accommodation can be regarded as a widespread pathophysiological alteration within the gastrointestinal (GI) tract. Colonic accommodation during colorectal distension (CRD) was assessed in Wistar Kyoto rats (WKY), an animal model of impaired gastric accommodation, and in Sprague-Dawley (SD) and Wistar rats, considered normal. CRD (10-80 mmHg)-induced visceral pain responses were also evaluated in the same strains of rats. During gastric distension, WKY rats had lower intra-gastric volume (0.96 +/- 0.22 ml) than SD (1.85 +/- 0.19 ml, P < 0.05) or Wistar rats (2.80 +/- 0.26 ml, P < 0.05), indicating impaired gastric accommodation. In the same animals, pressure-volume curves were constructed during CRD as a measure of colonic accommodation. During short-lasting (1 min) phasic CRD (2-20 mmHg), the pressure-volume curve in WKY rats was displaced to the right compared with SD or Wistar rats, indicative of reduced colonic accommodation (maximal volume: SD, 1.22 +/- 0.05 ml; Wistar, 1.07 +/- 0.04 ml; WKY, 0.87 +/- 0.07 ml; P < 0.01). Pre-treatment with atropine normalised the pressure-volume responses in WKY rats. No differences among strains were observed during the 2-min phasic or ramp-tonic CRD. Visceral pain responses during CRD (10-80 mmHg) were, overall, similar in the three strains, although WKY rats showed lower thresholds for pain (28.0 +/- 4.9 mmHg) than SD (42.3 +/- 6.6 mmHg, P = 0.072) or Wistar rats (48.3 +/- 6.0 mmHg, P < 0.05). WKY rats, although having impaired gastric accommodation, have the ability to fully accommodate the colon to increasing pressures. In WKY rats, impaired accommodation of the smooth muscle might not be a widespread phenomenon along the GI tract but rather a local disturbance.
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PMID:Characterisation of colonic accommodation in Wistar Kyoto rats with impaired gastric accommodation. 1790 48

Visceral pain is the most common reason for doctor visits in the US. Like somatic pain, virtually all visceral pain sensations begin with the activation of primary sensory neurons innervating the viscera and/or the blood vessels associated with these structures. Visceral afferents also play a central role in tissue homeostasis. Recent studies show that in addition to monitoring the state of the viscera, they perform efferent functions through the release of small molecules (e.g. peptides like CGRP) that can drive inflammation, thereby contributing to the development of visceral pathologies (e.g. diabetes Razavi, R., Chan, Y., Afifiyan, F.N., Liu, X.J., Wan, X., Yantha, J., Tsui, H., Tang, L., Tsai, S., Santamaria, P., Driver, J.P., Serreze, D., Salter, M.W., Dosch, H.M., 2006. TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes, Cell 127 1123-1135). Visceral afferents are heterogeneous with respect to their anatomy, neurochemistry and function. They are also highly plastic in that their cellular environment continuously influences their response properties. This plasticity makes them susceptible to long-term changes that may contribute significantly to the development of persistent pain states such as those associated with irritable bowel syndrome, pancreatitis, and visceral cancers. This review examines recent insights into visceral afferent anatomy and neurochemistry and how neonatal insults can affect the function of these neurons in the adult. New approaches to the treatment of visceral pain, which focus on primary afferents, will also be discussed.
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PMID:Development, plasticity and modulation of visceral afferents. 1915 Mar 71

1. The present review discusses interactions between the immune and nervous systems in post-infectious irritable bowel syndrome (PI-IBS). 2. Visceral pain is the single symptom that most affects the quality of life of patients with irritable bowel syndrome (IBS), yet it is the least successfully managed. An underlying hypersensitivity of colonic afferents to mechanical stimuli has long been implicated in visceral pain in IBS, but little more is known of the physiological aetiology. 3. The PI-IBS patients are a cohort of IBS patients who attribute their symptoms to a preceding gastrointestinal infection by pathogens such as Campylobacter or Salmonella. Current evidence suggests that the immune system remains activated in these patients and contributes to their visceral hypersensitivity. This is characterized by a shift in the phenotype of circulating immune cells towards a Type 1 (Th1 predominating) state. Products from these immune cells sensitize colonic afferents to mechanical stimuli. 4. Rectal instillation of trinitrobenzene sulphonic acid induces a Th1-mediated inflammatory response, consistent with clinical observations in PI-IBS. The visceral hypersensitivity observed in this model is biphasic, with an initial onset characterized by visceral hypersensitivity correlating with histological damage followed by a delayed phase that occurs after histological recovery. Interestingly, this chronic visceral hypersensitivity is mediated by afferents in closest apposition to blood vessels, but furthest from the initial site of damage. 5. Both clinical and experimental evidence indicates that chronic dysregulation of the immune system induces visceral afferent hypersensitivity and, therefore, may be the central mechanism underlying PI-IBS.
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PMID:Post-inflammatory modification of colonic afferent mechanosensitivity. 1956 23

Recent advances in brain science have shown that the brain function encoding emotion depends on interoceptive signals such as visceral pain. Visceral pain arose early in our evolutionary history. Bottom-up processing from gut-to-brain and top-down autonomic/neuroendocrine mechanisms in brain-to-gut signaling constitute a circuit. Brain imaging techniques have enabled us to depict the visceral pain pathway as well as the related emotional circuit. Irritable bowel syndrome (IBS) is characterized by chronic recurrent abdominal pain or abdominal discomfort associated with bowel dysfunction. It is also thought to be a disorder of the brain-gut link associated with an exaggerated response to stress. Corticotropin-releasing hormone (CRH), a major mediator of the stress response in the brain-gut axis, is an obvious candidate in the pathophysiology of IBS. Indeed, administration of CRH has been shown to aggravate the visceral sensorimotor response in IBS patients, and the administration of peptidergic CRH antagonists seems to alleviate IBS pathophysiology. Serotonin (5-HT) is another likely candidate associated with brain-gut function in IBS, as 5-HT3 antagonists, 5-HT4 agonists, and antidepressants were demonstrated to regulate 5-HT neurotransmission in IBS patients. Autonomic nervous system function, the neuroimmune axis, and the brain-gut-microbiota axis show specific profiles in IBS patients. Further studies on stress and visceral pain neuropathways in IBS patients are warranted.
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PMID:Stress and visceral pain: focusing on irritable bowel syndrome. 2402 63

Visceral pain has been defined as a pain resulting from activation of pain receptors localized in mucous membrane, serous membrane, and smooth muscles of hollow organs. The great majority of these organs are innervated by parasympathetic and sympathetic outflows. Afferent nerve fibres are involved in conduction of both acute and persistent pain and hyperalgesia. Visceral pain differs significantly from other types of pain in the way it originates and in clinical presentation. It can be misleading as a symptom, producing several problems in the diagnostic process. Sometimes, severe visceral pain is observed in the course of non-lifethreatening functional gastrointestinal disorders, while slight abdominal discomfort may be a first symptom of malignant tumours. For many years, the treatment of visceral pain has been considered as not satisfactory enough and covered a wide variety of pharmacological substances. For example, the complex therapy of pain and other manifestations associated with irritable bowel syndrome include psychotherapy/behavioural therapy, bulk-forming agents, probiotics, laxatives, antidiarrheals, antibacterial agents, antispasmodics, and antidepressants. The current knowledge about the pathogenesis of visceral pain gives a rationale for the development of new, more efficacious drugs with a positive benefit/risk ratio. Unfortunately, experience gained so far with the use of some agents affecting serotoninergic transmission in the gastrointestinal tract have shown a serious danger associated with their administration for patients with irritable bowel syndrome.
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PMID:Clinical approach to visceral pain in irritable bowel syndrome - pathophysiology, symptoms, and treatment. 2500 Aug 34


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