> Bill wrote:
> > I don't know if it is the injured cells themselves, but peripheral
> > sensitizors are all sorts of things, prostanoids, serotonin, adenosine,
> > neuropeptide Y, and some other peptide I'm forgetting...
> > There are lots of reviews on the subject, check out this one, free, for
> > instance:
> > http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7577246&query_hl=2&itool=pubmed_docsum>> That page talks about "sensitization" and inflammation. I wasn't
> referring to that.
>> I was trying to discuss the pain caused by the injured tissue *prior*
> to any inflammation or sensitization. I am talking about direct
> transduction of signals transferred from injured cells to sensory
>> For example, if you touch an extremely hot object, you will feel
> excruciating pain LONG before any inflammation or sensitization occurs.
The same cells that drive inflammation can also mediate pain. Mast
cells can degranulate very quickly, some immune cells can generate il-1
and tnfa in a flash, probably through intracellular stores in
non-active form. Eg. ICE will quickly turn il-1 into an active form and
il-1 can induce substance p release. Nitric oxide also is generated
very quickly because it is often constitutively expressed or its
precursors are quickly activated. il-1 is a big driver of nitric oxide
generation, I think, perhaps, maybe, this is via p38, a second
messenger. Don't think you need transcription to get these processes
going, if that were the case microbes would have a big headstart.
Microglia at the DRGs are strongly implicated in some types of
neuropathic pain, no need for sensory activation at all, direct impact
on conduction dynamics, perhaps, maybe ... . Don't know what "pain" is.
Dendritic cells, or in the case of skin, DC types called langerhan
cells, are probably implicated but I am not sure how quickly they ramp
up the juices.
Don't assume that inflammation is not happening quickly, mast cells,
il-1,tnfa, will rapidly generate inflammation that may not be obvious
at the macro level but looking deeper down you can often see
inflammation is already occurring. Nitric oxide is a good example of
this, rapidly diffuses throughout tissues, with a short half life, and
a strong vasodilator.
What might be worth looking at are Th 1 mediated processes. If you want
to understand pain at the cellular level, you're going to have to study
immunology. That will take a lifetime. Fascinating stuff, incredibly
complex, beyond systemisation because the "immune system" is a
misnomer. Evolution doesn't create systems, it creates responses.
I'm not very knowledgable about this stuff so you're on your own ... .
> In this case, the direct injury [i.e. thermal denaturation of the skin
> proteins] causes the damaged cells to secrete certain chemicals that
> stimulate nociceptors and VRL-1 [*not* to be confused with VR-1]
> receptors. Once again, this is DIRECT transduction [from a non-neural
> signal to a neural signal] and it occurs long before any inflammation
> or sensitization.