Modulation of the cardiac voltage-gated sodium channel by natural compounds

Irritable bowel syndrome (IBS) is the most common disorder presenting to gastroenterologists and is characterized by visceral hypersensitivity, defined by decreased pain and discomfort thresholds that may manifest as pain associated with bowel disturbances. Although the pathogenesis of visceral hypersensitivity is not fully understood several mechanisms have been proposed, some of them associated to a peripheral and central sensitization of visceral afferent neuronal pathways. Ion channels have been involved in this pain sensation pathways. There are evidences provided about the role of the cation channel TRPV1 in pain generation in IBS and its potential role for inflammation, augmented pain perception and hypersensitivity. But not only sensory TRP cation channels have been identified as possible trigger of hypersensitivity in IBS patients, voltage-gated sodium channels (VGSC) are also presents and it has been shown a clear reduction in rectal sensitivity and abdominal pain in patients with IBS treated with intrarectal administration of lidocaine (a classic local anesthetic compound because its well-known inhibition of VGSC).Recently in our lab we found that cinnamaldehyde (CA) and lidocaine share common structural determinants for the inhibition of VGSC channels and further support our conclusion that CA has local anesthetic actions. The aim of this project is to clarify the possible role of sensory TRP channels in IBS but also to assess the possible actions of CA on VGSC as a therapeutic target for the treatment of IBS.

Jaar van publicatie:2019