Peripheral contribution of NGF and ASIC 1a to colonic hypersensitivity in a rat model of irritable bowel syndrome - Archive ouverte HAL Access content directly
Journal Articles Neurogastroenterology & Motility Year : 2013

Peripheral contribution of NGF and ASIC 1a to colonic hypersensitivity in a rat model of irritable bowel syndrome

J. Matricon
  • Function : Author
E. Muller
  • Function : Author
A. Accarie
  • Function : Author
M. Meleine
  • Function : Author
M. Etienne
  • Function : Author
N. Voilley
  • Function : Author
J. Busserolles
  • Function : Author
A. Eschalier
  • Function : Author
M. Lazdunski
  • Function : Author
S. Bourdu
  • Function : Author
A. Gelot
  • Function : Author
D. Ardid
  • Function : Author

Abstract

Abstract Background Irritable bowel syndrome ( IBS ) is a functional gastrointestinal disorder associated with idiopathic colonic hypersensitivity ( CHS ). However, recent studies suggest that low‐grade inflammation could underlie CHS in IBS . The pro‐inflammatory mediator nerve growth factor ( NGF ) plays a key role in the sensitization of peripheral pain pathways and several studies have reported its contribution to visceral pain development. NGF modulates the expression of Acid‐Sensing Ion Channels ( ASIC s), which are proton sensors involved in sensory neurons sensitization. This study examined the peripheral contribution of NGF and ASIC s to IBS ‐like CHS induced by butyrate enemas in the rat colon. Methods Colorectal distension and immunohistochemical staining of sensory neurons were used to evaluate NGF and ASIC s contribution to the development of butyrate‐induced CHS . Key Results Systemic injection of anti‐ NGF antibodies or the ASIC s inhibitor amiloride prevented the development of butyrate‐induced CHS . A significant increase in NGF and ASIC 1a protein expression levels was observed in sensory neurons of rats displaying butyrate‐induced CHS . This increase was specific of small‐ and medium‐diameter L1 + S1 sensory neurons, where ASIC 1a was co‐expressed with NGF or trkA in CGRP ‐immunoreactive somas. ASIC 1a was also overexpressed in retrogradely labeled colon sensory neurons. Interestingly, anti‐ NGF antibody administration prevented ASIC 1a overexpression in sensory neurons of butyrate‐treated rats. Conclusions & Inferences Our data suggest that peripheral NGF and ASIC 1a concomitantly contribute to the development of butyrate‐induced CHS NGF ‐ ASIC 1a interplay may have a pivotal role in the sensitization of colonic sensory neurons and as such, could be considered as a potential new therapeutic target for IBS treatment.
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Dates and versions

hal-04317379 , version 1 (01-12-2023)

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J. Matricon, E. Muller, A. Accarie, M. Meleine, M. Etienne, et al.. Peripheral contribution of NGF and ASIC 1a to colonic hypersensitivity in a rat model of irritable bowel syndrome. Neurogastroenterology & Motility, 2013, 25 (11), pp.e740-54. ⟨10.1111/nmo.12199⟩. ⟨hal-04317379⟩

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