Post-inflammatory modification of colonic afferent mechanosensitivity

P. A. Hughes, S. M. Brierley, L. A. Blackshaw

Research output: Contribution to journalReview articlepeer-review

50 Citations (Scopus)

Abstract

The present review discusses interactions between the immune and nervous systems in post-infectious irritable bowel syndrome (PI-IBS). Visceral pain is the single symptom that most affects the quality of life of patients with irritable bowel syndrome (IBS), yet it is the least successfully managed. An underlying hypersensitivity of colonic afferents to mechanical stimuli has long been implicated in visceral pain in IBS, but little more is known of the physiological aetiology. The PI-IBS patients are a cohort of IBS patients who attri\~bute their symptoms to a preceding gastrointestinal infection by pathogens such as Campylobacter or Salmonella. Current evidence suggests that the immune system remains activated in these patients and contributes to their visceral hypersensitivity. This is characterized by a shift in the phenotype of circulating immune cells towards a Type 1 (Th1 predominating) state. Products from these immune cells sensitize colonic afferents to mechanical stimuli. Rectal instillation of trinitrobenzene sulphonic acid induces a Th1-mediated inflammatory response, consistent with clinical observations in PI-IBS. The visceral hypersensitivity observed in this model is biphasic, with an initial onset characterized by visceral hypersensitivity correlating with histological damage followed by a delayed phase that occurs after histological recovery. Interestingly, this chronic visceral hypersensitivity is mediated by afferents in closest apposition to blood vessels, but furthest from the initial site of damage. Both clinical and experimental evidence indicates that chronic dysregulation of the immune system induces visceral afferent hypersensitivity and, therefore, may be the central mechanism underlying PI-IBS.

Original languageEnglish
Pages (from-to)1034-1040
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Volume36
Issue number10
DOIs
Publication statusPublished or Issued - 28 Dec 2009
Externally publishedYes

Keywords

  • Cytokine
  • Gastrointestinal diseases
  • Infection/inflammation
  • Irritable bowel syndrome
  • Neuroimmunology
  • Pain
  • Sensory nervous system

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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