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Skin pain


FunTimes
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Hiya Fun....

...the eye part is really puzzling but it sounds like an entrapped/inflamed nerve. might try a capsaicin crème like Salonpas or a lidocaine/prilocaine crème...needless to say don't get either in your eye! the big hammer would be Botox injection if this becomes ongoing....probably good idea to check with a dermatologist...

...the other thing...and I forget the name but Batch explains it quite nicely....my hair  hurts after a bad hit(s) (and I'm mostly bald)….weirdest damn thing and actually one of the few things that got thru to folks I was trying to explain CH to...."wow, that must really be a bad headache if even your hair hurts" (figured they were relating it to a bad hangover)....quite long lasting but eventually faded...

Best

Jon

 

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Well the skin pain is almost 100% gone now. I have a feeling it has something to do with the a Pathway CH1 study I did a few years ago, now called Pulsante therapy. I think it messed with my nerves and causes some strange things to happen with my clusters and all the nerves in that area. 

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Hey Siegfried,

That's a new one on me... sounds more like the classic chicken or the egg conundrum...  which comes first...  The most common reason why triptans become ineffective other than overuse, is the flood of histamine released from mast cells during allergic reactions. The histamine triggers neurons within the trigeminal ganglia to express calcitonin gene-related peptide (CGRP) and Substance P (SP).   CGRP and SP are the two nuroactive peptides found elevated in serum concentrations during the pain phase of CH and MH.  They are responsible for the neurogenic inflammation and pain we know as CH and migraine... 

It gets worse...  CGRP in turn triggers mast cells to release even more histamine which triggers even more CGRP and SP in a circular chain reaction.  This results in what's called a CGRP cascade characterized by a spike in CH and MH frequency up to 8 attacks/day/night.  When this happens, none of the CH interventions are effective so we're considered to be refractory...

The best course of action in this case is to start a week to 10-Day course of a good first-generation antihistamine like Diphenhydramine (Benadryl).  Molecules of Diphenhydramine pass through the blood brain barrier to block histamine H1 receptors at the genetic layer.  This slows and can stop the circular chain reaction and CGRP cascade. 

Edited by Batch
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Hello Batch,

First time I heard this was from a neurologist interview somewhere on YouTube who told that.

I did some search myself and these articles indeed seems to confirm that:

https://www.medscape.org/viewarticle/464138

https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.10786

But these are migraine references. I do not know if it is the same for CH

Best Regards !

siegfried

 

 

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Hey Siegfried,

Thanks for the two links.  They make a lot more sense saying that once a migraine headache progresses to the point of cutaneous allodynia, triptans become far less effective as an abortive.  This jives with with the side effects of a CGRP cascade where both CH and MH become so severe in frequency, pain and duration, nothing works...

Thanks again,

V/R, Batch

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Siegfried,

A lot has happened in the field of molecular biology in the last 15 years since the two studies you referenced were conducted.  For example, sequencing of the human genome was largely complete in 2003 and finally completed with the sequencing of the last chromosome in 2006.  Since then there's been an explosion in the area of genetic mapping tools and today you can find several credible sites offering gene atlas like BioGPS that illustrate the distribution and density of specific genes.

Where all this applies to cluster and migraine headache takes us to the central dogma of molecular biology...  DNA <-> RNA -> Protein... essentially genetic expression.  The following graphic illustrates this process.

BFqhEOt.jpg

This process of genetic expression takes part in the nuclei in every cell type in the human body, in every chromosome and most genes.  Think of the messenger RNA (mRNA) in the graphic above as a sequence of genetic instructions, not unlike computer binary code, or a blue print that ribosomes (protein producing factories) within the cell cytoplasm use to translate or synthesize specific proteins called for in the mRNA blueprint. 

The four basic high level instructions in genetic expression are replication, differentiation, up- and down-regulation of protein synthesis and apoptosis, programmed cell death.

For example if the cell in the graphic above is a neuron within the trigeminal ganglia, the protein expressed above could easily be CGRP or SP in which case they would trigger the neurogenic inflammation and nociception, the pain we know as cluster or migraine headache. 

Now we can look at a scenario where vitamin D3 helps prevent CH and MH.  Although the exact mechanism(s) of action remain unclear, several studies have identified the likely candidates in this scenario.  The key candidates involved include molecules of the genetically active vitamin D3 metabolite 1,25(OH)2D3, several molecular forms of retinoic acid, (retinol, retinyl, referred to as reinoids), a vitamin D receptor (VDR) a retinoid-X receptor (RXR) and an RNA sequence.  It's interesting to note that the VDR and RXR are also products of genetic expression.

The following graphic illustrates where a molecule of 1,25(OH)2D3 and a molecule of retinoic acid combine to form a heterodimer, a two molecule polymer made of dissimilar molecules, that then attracts and attaches to a VDR and RXR.  This complex then attaches to the RNA portion of DNA at a Vitamin D Receptor Element (VDRE) to initiate transcription, the process of making an exact copy of the RNA sequence that's now called mRNA.

 

RWZ1C4L.jpg

This is where things get fuzzy...  The likely scenario here is where this particular process involves a genetic sequence responsible for expressing CGRP and in this case, vitamin D3 down-regulates its expression lowering the cellular concentration of CGRP to the point it is no longer capable of triggering CH.  Like I said, things get fuzzy here as a 2010 research study identified 2776 genomic positions occupied by the VDR and 229 genes with significant changes in expression in response to vitamin D3.

So there you have a Navy fighter pilot's thinking how vitamin D3 prevents CH...  and yes, I have a degree in chemistry circa '67.

Take care,

V/R, Batch

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