I last visited ch.com 3 years ago (Jan. 2014) when I became a member. After ~3 PF years the dance is beginning again….

I’m 63.5 yrs old now. Had my 1st ever ~3 month episodic attack during late Dec. 2009-late Mar 2010, so I’m one of those rare late-in-life starting CH sufferers. Took me a while to figure out what was wrong, like many at first I was absolutely convinced I had some kind of weird sinus infection (I’m a left-sider). After many GP and eye/ear/nose/throat doctor visits and CT scans I was getting angry at always hearing “there is nothing wrong we can find regards your sinuses”. I credit my wife with finding a CH ‘quiz’ on another medical site and when I realized all my answers were “Yes!” then at least I felt I knew what I was up against. I had not found this site at that time, so just muddled through the attacks until they tapered off and quit in late March 2010.

Then I had ~4 great PF years. I had retired from work in Sep. 2012 and started a consulting gig at the same time.  In late Dec. 2013 I felt weak shadows coming back (uh-oh) that got worse in Jan. 2014. My 2nd episodic attack again lasted ~3 months from early Jan. through end of Mar. 2014. But I had found this website (and Batch’s D3 regimen), and started taking D3 in early Feb. 2014. Unfortunately there was no measurable relief from the D3 regimen I undertook and again the attacks finally ran their course and ended in late Mar. 2014. At least I had discovered O2 this time around (and had a PCP that was willing to write a prescription for it), and it helped a lot with much of the pain. Unfortunately by the end of Feb. 2014 the lack of sleep from multiple night and day attacks made me very unfocused at work and I had to quit my consulting job.

Then I had another ~3 great PF years until a couple of weeks ago when I started failing the ‘beer test’ and knew my luck had run its course.

When I had my 2014 (2nd) episodic attack, the engineer in me thought that if I kept a detailed record of my attack severity and frequency then it might yield some trend information I could use to minimize the pain and episode length. So I started recording all of my attacks (attached).

My unscientific (and largely unproven) conclusions from 2014 are as follows:

1. When I looked at all the points plotted, they looked like just that – a bunch of dots on a page with little rhyme or reason. I could not drawn any definitive conclusions on the effectiveness of the D3 regimen, other than it MIGHT have started being effective in the beginning of Mar 2014.

2. I don’t think I was taking enough D3 early on (in Jan and Feb 2014). My baseline 25(OH)D was very low (13 ng/mL). I started at 10,000 IU/day D3, and did a couple of one-off 50,000 IU and 40,000 IU loading doses during the episode, but mainly was taking 10,000 IU/day. I am one of those people that hate to take ANY kind of medicine, so just going on the D3 regimen was a big deal for me, and in hindsight I should have questioned at the time if 10,000 IU/day was really enough to get me back to normal levels in a ~2 month period.
•      Now (Jan. 2017) I am on Batch’s updated (5 April 2016) anti-inflammatory regimen and have just finished 1 week of the 50,000 IU/day and will be doing the 40,000 IU/day for the next week.

3. O2 helped my pain most (but not all) of the time. I think my problem was that I was still ‘learning’ how to properly hyperventilate the O2 to maximum benefit.

4. Like others, I have some specific CH triggers (alcohol, sugar from candy, MSG?), but I am still learning what all my possible triggers might be. All of the data I collected from my 2014 episode might have made more sense if I had also kept a record of what exactly I ate each day. That is a lot of work but this time I am going to try to keep better records.

5. In 2014 I didn’t try Benadryl; I will be trying it this year if the D3 regimen remains ineffective.

I hope I can soon report back that I’m PF again. I am more confident this year that I’m combating the problem better than I did in 2014.

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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

As always, many thanks Batch for the reply and advice. I do tend to not drink as much water daily as I should, so I'll jump all over that now.

When I wrote the post I was on Day 7 of the 50k IU/day, and preparing for the week at 40k IU/day. I had been having 1 to 2 attacks a night (5 kip?) but on Wed. 25 Jan. I really got hammered with 4-5 attacks that night/early Thurs. morning getting in the 7-8 kip range. Lo and behold, on Thurs. night 26 Jan. I had zero/zilch/nada attacks. What a joy to sleep normally through the night!

I may have been having an allergic reaction earlier this week but I also think that my D3 level before starting the regimen this year probably was just severely depleted. I am hoping that the 1 week of 50k IU/day brought my 25(OH)D level to the tipping point.

"Rapid degranulation of mast cells" - wow you have done some fantastic research, I am impressed. If my attack-free night turns out to be an outlier I will certainly be trying Benadryl. But I am cautiously optimistic that I may have turned a corner and will know more after the week of 40k IU/day treatment.

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

Batch! This is all excellent information in this thread! I just posted to your main thread about having an allergic reaction which restarted my CHs, and I had been positing that >>something<< can trigger the histamine response without an outside allergen being present, and here you have already addressed this! You're amazing!

"...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 triggered by CGRP could easily explain the rapid spike in pain level during most CH."

Thank you once again for all your research and hard work on CH! I'm going to study the CGRP chain reaction in as much detail as I can! The next question I want answered is, in the absence of an allergen as the trigger, why does the Mast cell degranulation happen essentially on the circadian rhythm during a CH cycle? Why does this happen approximately every 12 or 24 hours?!