Quote:
Originally Posted by fmichael
Then in the same vein, we also have "Neurokinins enhance excitability in capsaicin responsive DRG neurons," Adrian Sculptoreanu and William C. de Groat, Exp. Neurol. 2007 May; 205(1): 92–100 [and once more, I'll be happy to send anyone a copy of this who wants it]:
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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):
Quote:
Na+ channel blockers for the treatment of pain: context is
everything, almost Published in final edited form as:
Exp Neurol. 2008 March ; 210(1): 1–6.
"As part of the rationale for focusing their study on NaV1.8, Yamane and colleagues summarize data implicating the involvement of this channel in the hyper-reflexia and hypersensitivity observed following inflammation of visceral structures.
and
It is important to point out, particularly within the context of the
study conducted by Yamane and colleagues, that decreasing NaV1.8 may effectively attenuate visceral hyper-reflexia, even if this channel is not the primary mechanism mediating the increase in excitability. For example, bladder inflammation results in a dramatic increase in
the excitability of bladder afferents that appears to reflect a decrease in voltage-gated K+ channels (Yoshimura and de Groat, 1999), yet knocking down NaV1.8 effectively reverses the inflammation-induced hyper-reflexia (Yoshimura, et al., 2001)."
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