That's an interesting paper. Since it seems to play a role in the severity of atopic dermatitis in humans, NGF should probably not be augmented if you have this condition. OTOH, their conclusion was a little unclear with regard to cause/effect (they say NGF-induced nerve growth causes itching "indirectly," implying that other factors are involved).
I've never read about hypersensitivity being encountered in any other studies involving mice, so this condition may need to preexist for this to occur. More generally, people have been using agents which increase NGF for hundreds of years, and for many decades in clinical application (i.e. lithium). The woman who discovered it has been applying it conjunctively for 20 years, apparently without problem. I would hesitate to say this is a real concern, though it's a possibility. If it is, it would probably happen gradually—not like you'd wake up in agony from the touch of your pajamas
But indeed, it raises the larger issue of unintended/negative consequences of playing with this potent nerve chemical. I certainly wouldn't want to imply that it's
safe for everyone (what is?), but so far all concerns seem to apply to isolated conditions (or pre-existing cancers). My feeling is that it poses little threat to the healthy. It's great that we're finding these possibilities, so they can be taken into account, or obviated.
But I do think downregulation (tolerance) to NGF inducing compounds is a very real possibility, and one which might apply to everyone who takes it for the long-term. I haven't seen the specific mechanism of inducing NGF expression mentioned yet, so it's going to take some more lateral and general research. But a search of papers shows that downregulation of NGF expression is
definitely possible in many instances. I find it somewhat hard to believe that you could convince your cells to pump out supernormal amounts of this growth factor for the rest of your life.
In cerebrolysin therapy for advanced alzheimer's (which in some cases produces remarkable results, due at least in part to NGF/BDNF), a standard treatment cycle is 5x/week for four weeks, then four weeks off. If this is done when there's every reason to try to promote as much nerve growth as possible, I'm hypothesizing that it's partly to prevent tolerance.
So I'm considering either an all-on/all-off cycle, or staggering substances which we know to work on different systems/mechanisms (i.e. endogenous inducers vs. direct growth stimulators). And maybe a 3-4 week on/1 week off cycle. Just a thought at this point, but I think that it might yield better results than a constant regimen of diminishing returns.
NDM: So you're still taking it, and no more nosebleeds? Do you get any of the lethargy/fatigue some people have described? At what time of day do you take it?
