American journal of physiology. Gastrointestinal and liver physiology
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Am. J. Physiol. Gastrointest. Liver Physiol. · Jun 2015
ReviewAnimal models of gastrointestinal and liver diseases. Animal models of visceral pain: pathophysiology, translational relevance, and challenges.
Visceral pain describes pain emanating from the thoracic, pelvic, or abdominal organs. In contrast to somatic pain, visceral pain is generally vague, poorly localized, and characterized by hypersensitivity to a stimulus such as organ distension. ⋯ This review focuses on animal models of visceral pain and their translational relevance. In addition, the challenges of using animal models to develop novel therapeutic approaches to treat visceral pain will be discussed.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Mar 2014
ReviewGranulocyte macrophage colony-stimulating factor and the intestinal innate immune cell homeostasis in Crohn's disease.
Current literature consolidates the view of Crohn's disease (CD) as a form of immunodeficiency highlighting dysregulation of intestinal innate immunity in the pathogenesis of CD. Intestinal macrophages derived from blood monocytes play a key role in sustaining the innate immune homeostasis in the intestine, suggesting that the monocyte/macrophage compartment might be an attractive therapeutic target for the management of CD. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that also promotes myeloid cell activation, proliferation, and differentiation. ⋯ However, the role of GM-CSF in immune and inflammatory reactions in the intestine is not well defined. Beneficial effects exerted by GM-CSF during intestinal inflammation could relate to modulation of the mucosal barrier function in the intestine, including epithelial cell proliferation, survival, restitution, and immunomodulatory actions. The aim of this review is to summarize potential mechanistic roles of GM-CSF in intestinal innate immune cell homeostasis and to highlight its central role in maintenance of the intestinal immune barrier in the context of immunodeficiency in CD.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Jul 2012
ReviewIrritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome.
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, characterized by recurrent abdominal pain or discomfort in combination with disturbed bowel habits in the absence of identifiable organic cause. Visceral hypersensitivity has emerged as a key hypothesis in explaining the painful symptoms in IBS and has been proposed as a "biological hallmark" for the condition. Current techniques of assessing visceral perception include the computerized barostat using rectal distensions, registering responses induced by sensory stimuli including the flexor reflex and cerebral evoked potentials, as well as brain imaging modalities such as functional magnetic resonance imaging and positron emission tomography. ⋯ This review aims to discuss currently used modalities in assessing visceral perception, along with advantages and limitations, and aims also to define future directions for methodological aspects in visceral pain research. Although novel paradigms such as brain imaging and neurophysiological recordings have been introduced in the study of visceral pain, confirmative studies are warranted to establish their robustness and clinical relevance. Therefore, subjective verbal reporting following rectal distension currently remains the best-validated technique in assessing visceral perception in IBS.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Feb 2001
ReviewStress and the gastrointestinal tract III. Stress-related alterations of gut motor function: role of brain corticotropin-releasing factor receptors.
Alterations of gastrointestinal (GI) motor function are part of the visceral responses to stress. Inhibition of gastric emptying and stimulation of colonic motor function are the commonly encountered patterns induced by various stressors. Activation of brain corticotropin-releasing factor (CRF) receptors mediates stress-related inhibition of upper GI and stimulation of lower GI motor function through interaction with different CRF receptor subtypes. CRF subtype 1 receptors are involved in the colonic and anxiogenic responses to stress and may have clinical relevance in the comorbidity of anxiety/depression and irritable bowel syndrome.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Apr 2000
ReviewPathobiology of visceral pain: molecular mechanisms and therapeutic implications. II. Genetic approaches to pain therapy.
New analgesic drugs are necessary because a number of pain states are untreatable. Genetic approaches to the identification of analgesic drug targets include mapping genes involved in human pain perception (e.g., trkA involved in hereditary neuropathies), identifying regulators of sensory neuron function in simple multicellular organisms and then investigating the activity of their mammalian homologs (e.g., POU domain transcription factors that specify sensory cell fate), as well as difference, expression, and homology cloning of receptors, ion channels, and transcription factors present in sensory neurons. After target validation through the construction of null mutant mice, high-throughput cell-based screens can be used to identify potential drug candidates. As a result of these approaches, a number of receptors and ion channels present in sensory neurons such as voltage-gated sodium channels [sensory neuron specific (SNS) and Na channel novel] and ATP-gated (P2X3), capsaicin-gated [vanilloid receptor 1(VR1)], and proton-gated [acid-sensing ion channel (ASIC)] channels are now under investigation as potential new analgesic drug targets.