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TRP channels: new targets for visceral pain
  1. L A Blackshaw1,2,3,
  2. S M Brierley1,2,
  3. P A Hughes1,2
  1. 1
    Nerve-Gut Research Laboratory, Department of Gastroenterology & Hepatology, Hanson Institute, Royal Adelaide Hospital, Adelaide, South Australia, Australia
  2. 2
    Discipline of Physiology, School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide, South Australia, Australia
  3. 3
    Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
  1. Correspondence to Professor L A Blackshaw, Nerve-Gut Research Laboratory, Department of Gastroenterology & Hepatology, Hanson Institute, Royal Adelaide Hospital, Adelaide, South Australia, Australia 5000; ashley.blackshaw{at}adelaide.edu.au

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Introduction

How often do gastroenterologists advise patients to “avoid spicy food” without really knowing why? The answer may lie in the family of transient receptor potential (TRP) channels, which includes receptors for compounds found in common herbs and spices. This aim of this review is not really to answer this question, but it will shed light on why spices may cause symptoms. Instead, its aim is to explore the TRP family for potential targets that may in fact reduce gut symptoms. Chronic pain and discomfort of unknown origin in functional gastrointestinal disorders represent a large unmet need for treatment and consequent economic impact. There are also features of other gut disease which generate symptoms with obscure origins. In order to understand how symptoms are generated in the gut and transmitted to the central nervous system, we need to know at least three principles of extrinsic sensory nerve function—first, what types are there and what do they signal?; secondly, what is the molecular basis of sensory transduction?; and thirdly, how does all of this change in disease? These questions are a key focus of this article, with a particular emphasis on the role of TRP channels in each case. Although there are no drugs yet available for clinical use that target TRP channels, some of the early pointers are identified that hold promise for their use in pharmacotherapy of gastrointestinal sensory dysfunction.

Detection and signalling of gut symptoms

Subtypes of sensory fibres

Peripheral endings of sensory afferent fibres can be classified into five subtypes in the mouse gastrointestinal tract according to the location of their mechanoreceptive fields.1 2 These are: mucosal, muscular (or tension receptor), muscular–mucosal (or tension–mucosal), serosal and mesenteric afferents (fig 1).1 2 3 4 Mucosal afferents respond exclusively to fine tactile stimulation of the luminal surface. Anatomically, they appear as bare endings in the lamina propria …

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