fredag den 31. januar 2014

TRPA1, LPS and the possible connection to ME symptoms

I would like to place this article
TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
in the line of my reflections on ME/CFS/POTS/MCS-symptoms and TRPA1 activation.

Lipopolysaccharide (LPS) also known as bacterial endotoxins, and endogenous TRPA1 agonists have synergistic effects. Reactive oxygen species (ROS) are TRPA1 agonists.

If we combine this knowledge with the theory of central sensitization,
Excessive activation of TRPA1 and TRPV1 by ROS may induce central sensitization – does it concern ME?
we might understand why Maes and Leunis have helped ME/CFS patients by lowering the LPS burden:
Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria

LPS produces a strong fall in blood pressure within minutes of injection, and TRPA1 appears to participate in the vasodilation response to LPS. I have previously written about the hypothesis that TRPA1 could be involved in the co-morbidity POTS, because of this arcticle: 
Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo:  "TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders".

Activation of TRPA1 is certainly involved in environmental exposure to chemicals:
Transient receptor potential channels and occupational exposure and Transient Receptor Potential in Multiple Chemical Sensitivity.

So, the question I keep coming back to: Is sustained firing of TRPA1 elicited by reactive agonists involved in ME symptoms? And will removal (reduction) of TRPA1 agonists attenuate ME symptoms?

LPS cause priming of microglia, and this may lead to progression of pre-existing neurodegenerative disease. Microglia priming - a role in ME?

Caveolae, eNOS and TRPA1?

Ingen kommentarer:

Send en kommentar

Bemærk! Kun medlemmer af denne blog kan sende kommentarer.