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Type: Journal article
Title: Selective role for TRPV4 ion channels in visceral sensory pathways
Author: Brierley, S.
Page, A.
Hughes, P.
Adam, B.
Liebregts, T.
Isaacs, N.
Holtmann, G.
Liedtke, W.
Blackshaw, L.
Citation: Gastroenterology, 2008; 134(7):2059-2069
Publisher: W B Saunders Co
Issue Date: 2008
ISSN: 0016-5085
Statement of
Stuart M. Brierley, Amanda J. Pagelo, Patrick A. Hughes, Birgit Adam, Tobias Liebregts, Nicole J. Cooper, Gerald Holtmann, Wolfgang Liedtke and L. Ashley Blackshaw
Abstract: <h4>Background & aims</h4>Although there are many candidates as molecular mechanotransducers, so far there has been no evidence for molecular specialization of visceral afferents. Here, we show that colonic afferents express a specific molecular transducer that underlies their specialized mechanosensory function: the transient receptor potential channel, vanilloid 4 (TRPV4).<h4>Methods</h4>We found TRPV4 mRNA is highly enriched in colonic sensory neurons compared with other visceral and somatic sensory neurons. TRPV4 protein was found in colonic nerve fibers from patients with inflammatory bowel disease, and it colocalized in a subset of fibers with the sensory neuropeptide CGRP in mice. We characterized the responses of 8 subtypes of vagal, splanchnic, and pelvic mechanoreceptors.<h4>Results</h4>Mechanosensory responses of colonic serosal and mesenteric afferents were enhanced by a TRPV4 agonist and dramatically reduced by targeted deletion of TRPV4 or by a TRP antagonist. Other subtypes of vagal and pelvic afferents, by contrast, were unaffected by these interventions. The behavioral responses to noxious colonic distention were also substantially reduced in mice lacking TRPV4.<h4>Conclusions</h4>These data indicate that TRPV4 contributes to mechanically evoked visceral pain, with relevance to human disease. In view of its distribution in favor of specific populations of visceral afferents, we propose that TRPV4 may present a selective novel target for the reduction of visceral pain, which is an important opportunity in the absence of current treatments.
Keywords: Colon
Afferent Pathways
Neurons, Afferent
Enteric Nervous System
Mice, Knockout
Inflammatory Bowel Diseases
Calcitonin Gene-Related Peptide
RNA, Messenger
Pain Measurement
Models, Animal
Behavior, Animal
Pain Threshold
Mechanotransduction, Cellular
TRPV Cation Channels
DOI: 10.1053/j.gastro.2008.01.074
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