Hey Bug,

You're off to a great start with the anti-inflammatory regimen.  That said, a week of vitamin D3 at 50,000 IU/day should have started a downward shift in the frequency, severity and duration of your CH (Great charts) unless your 25(OH)D serum concentration is still in the dumper or you're dehydrated.  Start pushing fluids up to 2.5 liters of water a day.

The more likely reason for no response at this point is you may be having an allergic reaction.  They can be subclinical, i.e., no obvious or outward symptoms usually associated with an allergy... but the allergic reaction is still there triggering Mast cells throughout the brain to pump out a flood of histamine. 

I went back over the literature on the pathogenesis of allergic reactions then connected the dots with respect to their association with CH.  I think you’ll find what I pieced together not only fascinating, but also helpful in understanding how allergies affect us as CHers.

It all starts with Mast Cells, a type of white blood cell that’s part of our immune system.  They are found in tissues throughout the body primarily in mucus membranes lining breathing passages and the GI tract, but they are also found around capillaries throughout the body.  It’s these strategic locations that provide mast cells with the opportunity to defend the body against invading pathogens and allergens.

Mast cells are loaded with “granules” filled with all kinds of things our immune system uses to combat pathogens and allergens as illustrated in the following electron microscope image.  As I spent many years in the military, I liken mast cells to an IED/Cluster Bomb spring loaded to  the pissed off position… 

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All it takes is an insult from a pathogen or allergen and mast cells can either selectively release the contents of these granules or explode (degranulate) rapidly as the cellular biologists call it, releasing a boatload of nature’s pharmaceutical products… in most cases, designed to keep us healthy…  However, if the degranulation is widespread and occurs too rapidly, anaphylactic shock can occur. 

In our case as CHers, degranulation releases a flood of histamine and that results in a humongous CH triggering mechanism…  The following graphic illustrates the products of mast cell degranulation.

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As a result of this mast cell degranulation, histamine is released and it in turn, triggers neurons throughout the brain and in particular, the trigeminal ganglia to release calcitonin gene-related peptide (CGRP) and Substance P (SP).  Both trigger neurogenic inflammation and CGRP is directly associated with the terrible pain of CH.  It gets worse…

The CGRP released in this process in turn triggers mast cells to release more histamine resulting in a bi-directional or circular chain reaction that continues until the reactants are consumed… at which point the CH attack ends… for now… 

I am quite confident that the histamine released as a result of an allergic reaction is responsible for many CHers being refractory to nearly all means of intervention, i.e., oxygen therapy not effective or less effective at best and traditional CH preventatives like verapamil either don’t work or their preventative effect is minimal.  It’s also very likely this flood of histamine is responsible for busting to become ineffective.

I've found Children's Liquid Benadryl (Diphenhydramine HCL) works just fine in slowing/stopping the histamine - CGRP chain reaction.  I take 12.5 mg (5 mL in the measuring cap) in the morning and another 12.5 mg prior to bed.  This works just as good and possibly a little faster than the 25 mg Benadryl tablets. 

It helps if you hold the liquid in your mouth, under your tongue and between cheek and gums for a few minutes.  This sublingual application gets the Diphenhydramine into the bloodstream faster than swallowing the Benadryl tablets.  The lower Diphenhydramine dose with Liquid Benadryl also helps lessen the drowsiness associated with this antihistamine.

Blocking or slowing the histamine - CGRP chain reaction gives the genetically active vitamin D3 metabolite 1,25(OH)2D3, calcitriol a chance to downregulate/suppress CGRP production through genetic expression... and... if my theory holds water... this prevents CH.

If there's no joy after 3 to 4 days of Benadryl (Diphenhydramine HCL), an allergic reaction may not be the culprit.  The next step is a 1,000 mg tablet of vitamin C (Ascorbic Acid) every two hours throughout the day and prior to bed.  If that doesn't have the CH beast on the run after a few days, add 500 mg/day curcumin with meals.

Hope this helps.  Please keep us posted.

V/R, Batch

Hey Bug,

Thanks for the update...  I like the positive trajectory... Hang tough and stick with the loading schedule as you've good indications you're near the tipping point.

If you follow my epistle on histamine, you'll see there's a logical reason to say the circular CGRP - Histamine chain reaction likely takes place without being triggered by an allergic reaction.  Mast cell degranulation and release of histamine triggerd by CGRP could easily explain the rapid spike in pain level during most CH.

Take care and please keep us posted.

V/R, Batch