Gastrointestinal afferents as targets of novel drugs for the treatment of functional bowel disorders and visceral pain

Eur J Pharmacol. 2001 Oct 19;429(1-3):177-93. doi: 10.1016/s0014-2999(01)01319-x.

Abstract

An intricate surveillance network consisting of enteroendocrine cells, immune cells and sensory nerve fibres monitors the luminal and interstitial environment in the alimentary canal. Functional bowel disorders are characterized by persistent alterations in digestive regulation and gastrointestinal discomfort and pain. Visceral hyperalgesia may arise from an exaggerated sensitivity of peripheral afferent nerve fibres and/or a distorted processing and representation of gut signals in the brain. Novel strategies to treat these sensory bowel disorders are therefore targeted at primary afferent nerve fibres. These neurons express a number of molecular traits including transmitters, receptors and ion channels that are specific to them and whose number and/or behaviour may be altered in chronic visceral pain. The targets under consideration comprise vanilloid receptor ion channels, acid-sensing ion channels, sensory neuron-specific Na(+) channels, P2X(3) purinoceptors, 5-hydroxytryptamine (5-HT), 5-HT(3) and 5-HT(4) receptors, cholecystokinin CCK(1) receptors, bradykinin and prostaglandin receptors, glutamate receptors, tachykinin and calcitonin gene-related peptide receptors as well as peripheral opioid and cannabinoid receptors. The utility of sensory neuron-targeting drugs in functional bowel disorders will critically depend on the compounds' selectivity of action for afferent versus enteric or central neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chest Pain / drug therapy
  • Chest Pain / physiopathology
  • Colonic Diseases, Functional / drug therapy
  • Colonic Diseases, Functional / physiopathology
  • Drug Delivery Systems*
  • Dyspepsia / drug therapy
  • Dyspepsia / physiopathology
  • Gastrointestinal Diseases / drug therapy*
  • Gastrointestinal Diseases / metabolism
  • Gastrointestinal Diseases / physiopathology*
  • Humans
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology*