Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
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Neurogastroenterol. Motil. · Jun 2012
Randomized Controlled TrialThe effect of baclofen on nocturnal gastroesophageal reflux and measures of sleep quality: a randomized, cross-over trial.
Baclofen, a GABA(b) agonist, has been shown to reduce episodes of gastroesophageal reflux (GER). To determine if baclofen would significantly reduce reflux during sleep, and also improve objective and subjective measures of sleep. ⋯ In addition to reducing the number of reflux events during sleep, baclofen significantly improved several measures of sleep in patients with documented GER and sleep disturbances. Baclofen could therefore be considered as a useful adjunct therapy to proton pump inhibitors (PPIs) in patients with nighttime heartburn and sleep disturbance who continue to have heartburn and/or sleep complaints despite PPI therapy.
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Neurogastroenterol. Motil. · Jun 2012
Colonic inflammation up-regulates voltage-gated sodium channels in bladder sensory neurons via activation of peripheral transient potential vanilloid 1 receptors.
Primary sensory neurons express several types of ion channels including transient receptor potential vanilloid 1 (TRPV1) and voltage-gated Na(+) channels. Our previous studies showed an increased excitability of bladder primary sensory and spinal neurons triggered by inflammation in the distal colon as a result of pelvic organ cross-sensitization. The goal of this work was to determine the effects of TRPV1 receptor activation by potent agonists and/or colonic inflammation on voltage-gated Na(+) channels expressed in bladder sensory neurons. ⋯ These results provide evidence that colonic inflammation activates TRPV1 receptors at the peripheral sensory terminals leading to an up-regulation of voltage gated Na(+) channels on the cell soma of bladder sensory neurons. This mechanism may underlie the occurrence of peripheral cross-sensitization in the pelvis and functional chronic pelvic pain.
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Neurogastroenterol. Motil. · May 2012
Evaluating symptom outcomes in gastroparesis clinical trials: validity and responsiveness of the Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD).
Patient-reported symptom scales are needed to evaluate treatments for gastroparesis. The Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) was developed to assess daily symptoms of gastroparesis. This study evaluated the validity and responsiveness of the GCSI-DD in patients with gastroparesis. ⋯ Symptoms of early satiety, nausea, postprandial fullness, and bloating were responsive to treatment for gastroparesis. A composite of these symptoms also demonstrates validity and responsiveness to treatment for gastroparesis, and may represent an acceptable endpoint for evaluating the effectiveness of medical treatments in clinical trials for gastroparesis.
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Neurogastroenterol. Motil. · May 2012
Importance of stress receptor-mediated mechanisms in the amygdala on visceral pain perception in an intrinsically anxious rat.
Stress worsens abdominal pain experienced by patients with irritable bowel syndrome (IBS), a chronic disorder of unknown origin with comorbid anxiety. Previously, we have demonstrated colonic hypersensitivity in Wistar-Kyoto rats (WKYs), a high-anxiety strain, which models abdominal pain in IBS. In low-anxiety rats, we have demonstrated that the central nucleus of the amygdala (CeA) regulates colonic hypersensitivity and anxiety induced by selective activation of either glucocorticoid receptors (GR) or mineralocorticoid receptors (MR), which is also mediated by the corticotropin releasing factor (CRF) Type-1 receptor. The goal of the present study was to test the hypothesis that the CeA through GR, MR, and/or CRF-1R regulates colonic hypersensitivity in WKYs. ⋯ Stress hormones in the CeA regulate colonic hypersensitivity in the rat through strain-dependent parallel pathways. The colonic hypersensitivity in WKYs is mediated by a CRF-1R mechanism in the CeA, independent of GR and MR. These complementary pathways suggest multiple etiologies whereby stress hormones in the CeA may regulate abdominal pain in IBS patients.
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Neurogastroenterol. Motil. · Mar 2012
Peripheral α-helical CRF (9-41) does not reverse stress-induced mast cell dependent visceral hypersensitivity in maternally separated rats.
Acute stress-induced hypersensitivity to colorectal distention was shown to depend on corticotropin releasing factor (CRF)-induced mast cell degranulation. At present it remains unclear whether CRF also induces chronic poststress activation of these cells. Accordingly, the objective of this study was to compare pre- and poststress CRF-receptor antagonist treatment protocols for their ability to, respectively, prevent and reverse mast cell dependent visceral hypersensitivity in a rat model of neonatal maternal separation. ⋯ Water avoidance-stress leads to persistent mast cell dependent visceral hypersensitivity in maternally separated rats, which can be prevented, but not reversed by blockade of peripheral CRF-receptors. We conclude that persistent poststress mast cell activation and subsequent visceral hypersensitivity are not targeted by CRF-receptor antagonists.