Abstract| Volume 177, ISSUE 1, P28, August 2013

Extrinsic Sensory Signalling – from Molecules to Drugs

      One of the hallmarks of IBS is visceral hypersensitivity. Understanding the molecular basis of hypersensitivity therefore offers a rationale for novel therapeutics aimed at treating pain and discomfort. A subset of patients report the onset of their IBS symptoms to a bout of gastroenteritis – so called post-infectious IBS, thus implicating an inflammatory trigger for hypersensitivity. We have developed an animal model to explore the link between gut immune activation and the long-term changes in sensory signalling that underlie visceral hypersensitivity. Our model utilizes an intestinal nematode Trichinella spiralis, which triggers a transient inflammatory response, that resolves spontaneously following worm expulsion. Post-infection we observe a persistent hypersensitivity to distension which we monitor using electrophysiological techniques that distinguish between altered excitability arising from phenotypic changes in ion channels expressed on sensory neurones and peripheral changes in the chemical milieu that influences sensory signal transduction via ligand-gated ion channels are receptors. These changes contribute to peripheral sensitization and represent potential targets for treatment. These targets can be validated using pharmacological tools which modulate ion channels and receptors or by the use of mouse transgenics to identify pivotal components in neuro-immune interactions. These point towards a critical role for mast cells and macrophages in modulating sensory signalling but there are issues around translation that have impact on drug discovery efforts. Nevertheless, key components of these neuro-immune interactions correlate with studies using patient biopsies, which reflect changes in the intestinal milieu as a disease biomarker and moreover offer mechanistic understanding of pain signalling in IBS.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect