Quote:
Originally Posted by Dr Adrian
Your mention of my article brought me to this forum...there is actually a connection between neurokinins and Na channels in nociceptive (pain) neurons which I am presently investigating. Turns out that neurokinins stimulate Na channles; particularly the tetrodotoxin-resistant subtype (Nav1.9) which has more recently been associated with development of chronic pain; that may account in part for the increase in excitability caused by neurokinins. There is a wide interest in the pharmaceutical industry at present to develop drugs that are selective blockers of this Na channel subtype and it is hope may selectively influence (inhibit) abnormal electrical activity in pain neurons. We have evidence to support this assertion:
"26. Yamane H, de Groat WC, Sculptoreanu A. (2007) Effects of ralfinamide, a Na+ channel blocker, on firing properties of nociceptive dorsal root ganglion neurons of adult rats. Exp Neurol. 208(1):63-72."
To qote the highlight of one of my colleagues (Michael Gold):
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Thanks for discussing my articles, I am the guy who did the work, Adrian Sculptoreanu. There are many interesting things still emerging from my early studies..among them Na channels are definitely a target of neurokinin modulation via erk kinase. That could be theoretically why during inflammation phosphorylated channels have higher affinities for certain local anesthetics. The autofeedback mechanism responsible for switching on C-fiber neurons are more complex and may involve several channels that may include TRP in addition to a slew of voltage dependent channels. For example SP and endothelin (released by some tumors) interact synergistically to produce very large increases in depolarizing TRPC currents (non selective cation channels)...so if I had the money to continue this research there are many dfirections it could take. For now I am in Italy enjoying the good weather...
07-16-2013, 06:36 AM
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