Acid-sensing ion channels (ASICs) are expressed by rat sensory neurons and may mediate pain associated with tissue acidosis after inflammation or injury.
A group based in London, England and Palo Alto, California, USA, has now examined human intestine and dorsal root ganglia to determine the molecular forms and localization of these channels in human tissue.
They also measured the effect that inflammation and injury had on the presence of these potential pain mediators.
Inflamed Crohn's disease intestine and injured human dorsal root ganglia, with appropriate controls, were studied by Western blotting and immunohistochemistry, using specific affinity-purified ASIC antibodies.
Western-blotting revealed a significant three-fold increase in the mean relative optical density of only the type 3 ASIC molecular form, both in full-thickness inflamed intestine, and in separated muscle and mucosal layers. This was not the case for the type 1 or type 2 forms of the protein.
| ASIC-3 levels were elevated in inflamed intestine |
| European Journal of Gastroenterology and Hepatology|
A corresponding trend for an increased immunoreactive density and raised number of ASIC-3-positive neurons in the myenteric and sub-mucous plexus of inflamed tissue was also observed using immunohistochemistry.
In dorsal root ganglia, immunohistochemistry indicated the presence of all ASICs in a restricted subpopulation (about 50%) of small diameter (nociceptor) sensory neurons. This pattern was generally less intense after injury.
The research group concludes from their findings that the presence of increased ASIC-3 in inflamed intestine suggests a role in pain or dismotility. ASICs may therefore represent new therapeutic targets for Crohn's disease.