title: Neuroimmune factors in functional gastrointestinal disorders: A focus on irritable bowel syndrome.
abstract: BACKGROUND
  Abnormal abdominal pain perception is the most bothersome and difficult to treat symptom of functional gastrointestinal disorders (FGIDs). Visceral pain stimuli are perceived and transmitted by afferent neurons residing in the dorsal root ganglia that have sensory nerve endings in the gut wall and mesentery. Accumulating evidence indicates that peripheral activation and sensitization of these sensory nerve endings by bioactive mediators released by activated immune cells, in particular mast cells, can lead to aberrant neuroimmune interactions and the development and maintenance of visceral hypersensitivity. Besides direct neuronal activation, low concentrations of proteases, histamine, and serotonin can chronically sensitize nociceptors, such as TRP channels, leading to persistent aberrant pain perception.
  
  
  OBJECTIVE
  This review discusses the potential mechanisms underlying aberrant neuroimmune interactions in peripheral sensitization of sensory nerves. A better understanding of the cells, mediators, and molecular mechanisms triggering persistent aberrant neuroimmune interactions brings new insights into their contribution to the physiology and pathophysiology of visceral pain perception and provides novel opportunities for more efficient therapeutic treatments for these disorders.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven University, Leuven, Belgium.
authors.forename: G E
authors.initials: GE
authors.lastname: Boeckxstaens
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven University, Leuven, Belgium.
authors.forename: M M
authors.initials: MM
authors.lastname: Wouters
mesh_terms: D015746:Abdominal Pain / Q000276:immunology; D000818:Animals; D005767:Gastrointestinal Diseases / Q000276:immunology*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D015213:Neuroimmunomodulation; D009474:Neurons / Q000276:immunology; D058748:Pain Perception / Q000502:physiology
keywords: (low-grade) inflammation; TRP channels; food antigens; pain