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Role of ion channels in mechanisms controlling gastrointestinal pain pathways

Fernando Cervero1, Jennifer M A Laird

  • 1Anaesthesia Research Unit, McGill University, McIntyre Medical Building, Room 1207, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6 Canada. fernando.cervero@mcgill.ca

Current Opinion in Pharmacology
|December 3, 2003
PubMed

Insights

Gastrointestinal pain may stem from hypersensitive gut nerves. Key ion channels, particularly the Na(v)1.8 sodium channel, play a crucial role in this nerve sensitization, contributing to pain.

Area of Science:

  • Neuroscience
  • Gastroenterology
  • Pain Research

Background:

  • Gastrointestinal (GI) pain, both organic and functional, is often linked to hypersensitivity of nociceptive primary afferents in the gut.
  • This hypersensitivity can arise from changes in the functional properties of ion channels within these primary afferents, potentially due to sensitizing agents or other causes.

Purpose of the Study:

  • To explore the role of ion channels in the sensitization of gastrointestinal primary afferents.
  • To identify key molecular players, such as specific sodium channels, involved in the generation and maintenance of GI pain states.

Main Methods:

  • Review and synthesis of existing literature on nociceptor sensitization and ion channel function in the GI tract.
  • Focus on the involvement of voltage-gated ion channels, including sodium, calcium, and potassium channels.

Main Results:

  • The tetrodotoxin-resistant sodium channel, Na(v)1.8, is identified as a primary candidate for enhanced activity in sensitized nociceptors of the gut.
  • Alterations in the functional properties of Na(v)1.8 channels are strongly implicated in the hypersensitivity underlying GI pain.

Conclusions:

  • Sensitization of gastrointestinal primary afferents, particularly involving the Na(v)1.8 channel, is a significant mechanism for GI pain.
  • Voltage-gated calcium and potassium channels may also contribute to the afferent sensitization observed in various GI pain conditions.

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