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Modulation of enteric neurons by interleukin‐6 and corticotropin‐releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome

Overview of attention for article published in Journal of Physiology, October 2014
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Title
Modulation of enteric neurons by interleukin‐6 and corticotropin‐releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome
Published in
Journal of Physiology, October 2014
DOI 10.1113/jphysiol.2014.279968
Pubmed ID
Authors

Maria M. Buckley, Ken D. O'Halloran, Mark G. Rae, Timothy G. Dinan, Dervla O'Malley

Abstract

The search for effective therapeutic strategies for irritable bowel syndrome (IBS) is hampered by an incomplete understanding of its underlying pathophysiology. Stress has been linked with IBS symptom flares and altered plasma cytokine profiles which are indicative of immune activation, are characteristic of the disorder. The neuromodulatory effects of interleukin (IL)-6 and corticotropin-releasing factor receptor (CRFR) 1 in visceral pain and stress-induced defecation in the Wistar Kyoto (WKY) rat model of IBS were investigated. Sprague Dawley and WKY rats were administered anti-IL-6 receptor antibodies (xIL-6R, 0.5 mg/kg intraperitoneally) with or without the CRFR1 antagonist, antalarmin (10 mg/kg intraperitoneally). Post-intervention, the pain threshold to colorectal distension and stress-induced faecal output were compared and changes in colonic mucosal protein expression were investigated. The neuro-stimulatory effects of IBS plasma on the myenteric plexus is mediated by IL-6, IL-8 and CRF. The stimulatory effects of these soluble factors on myenteric neuron excitability and colonic contractility were additive. Moreover, inhibition of IL-6 and CRF1 receptors in vivo in the WKY IBS rat model normalized stress-induced defecation (p<0.01) and visceral pain sensitivity (p<0.001) with associated changes in protein expression of the tight junction proteins, occludin and claudin 2, the visceral pain-associated T-type calcium channel, Cav3.2 and intracellular signalling molecules, STAT3, SOCS3 and ERK1/2. These studies demonstrate the additive effects of immune and stress factors on myenteric neuronal excitability. Moreover, combined targeting of peripheral IL-6 and CRF1 receptors is effective in alleviating IBS-like symptoms in the WKY rat. Thus, crosstalk between stress and immune factors during IBS flares may underlie symptom exacerbation. This article is protected by copyright. All rights reserved.

Mendeley readers

The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 60 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 16%
Student > Bachelor 9 15%
Researcher 8 13%
Student > Master 8 13%
Student > Doctoral Student 3 5%
Other 12 20%
Unknown 11 18%
Readers by discipline Count As %
Medicine and Dentistry 13 21%
Agricultural and Biological Sciences 9 15%
Neuroscience 8 13%
Nursing and Health Professions 4 7%
Psychology 4 7%
Other 8 13%
Unknown 15 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 December 2014.
All research outputs
#10,631,496
of 13,359,553 outputs
Outputs from Journal of Physiology
#5,903
of 6,789 outputs
Outputs of similar age
#141,542
of 212,437 outputs
Outputs of similar age from Journal of Physiology
#27
of 43 outputs
Altmetric has tracked 13,359,553 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,789 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.3. This one is in the 6th percentile – i.e., 6% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 212,437 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 43 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.