Hey Yucca,

I think your 2 cents worth of Top-Down Thoughts on the cause of CH are on the right track.  Are you a member of the cluster headache group Kokemusasiantuntija - Hortonin neuralgia - Puheenjohtaja, Suomen Horton-yhdistys
Multimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or in Finland run by Tony Taipale, a.k.a., "Tony Only"?  Tony is very familiar with the anti-inflammatory regimen of 10,000 IU/day vitamin D3 and cofactors that help prevent cluster headache (CH), migraine headache (MH) and the other TACs.

There are several CH studies that have found there are four primary neuropeptides associated with the cluster headache syndrome.  Calcitonin Gene-Related Peptide (CGRP), Substance P (SP), Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP). All are potent vasodilators and CGRP is responsible for the nociception, the CH pain we experience.  All are also present in the bloodstream during ictus (the painful CH attack).  Accordingly it's very likely, a dog's keen sense of smell can detect these neuropeptides in exhaled breath and skin of cluster headache sufferers (CHers) when in a CH bout.

The study I've been running for the last 9 years of CHers taking the anti-inflammatory regimen of 10,000 IU/day of vitamin D3 and its cofactors has produced some very interesting results.  For example, of the 313 CHers in this study who have started this treatment protocol over the last 9 years, all had a 25(OH)D3 serum concentration less than 47 ng/mL (62 nmol/L) with a mean 25(OH)D3 serum concentration of 24 ng/mL (60 nmol/L). 25(OH)D3 is the first metabolite of vitamin D3 that's used to measure its status before starting vitamin D3 therapy.

Of these 313 CHers, 66% were vitamin D3 insufficient and 33% were vitamin D3 deficient as illustrated in the following normal distribution curve of 25(OH)D3 lab results.

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If CHers followed this vitamin D3 treatment protocol for at least 30 days and obtained a second lab test for their serum 25(OH)D3, 82% experienced a significant reduction in the frequency of their CH from a mean of 3 CH/day down to 3 CH/week as illustrated in the following normal distribution chart of their 25(OH)D3 lab results after treatment.  52% of CHers following this treatment protocol experienced a complete and lasting cessation of CH symptoms as long as they kept taking this vitamin D3 regimen.  As you can see, the mean 25(OH)D3 serum concentration is 80 ng/mL, (200 nmol/L).

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From this data we can conclude there's an inverse relationship between the frequency of CH and vitamin D3 status as measured with the lab test for serum 25(OH)D3.  Some additional research indicates this inverse relationship can be classified as a genetotrophic disorder where genetically determined metabolic and nutritional needs are not being met.  There are several dificiency disorders like this including Rickets (Vitamin D3 Deficiency) Scurvy (Vitamin C Deficiency), Beri Beri and Palegra (Vitamin B1 Thiamine and Vitamin B2 riboflavin deficiencies).

This means CH is a nutritional deficiency disorder and not just a neurological disorder.  As most neurologists never study nutritional disorders, it's no wonder why they have difficulty in successfully treating patients with CH.  It turns out migraine and the rest of the TACs also respond to vitamin D3 therapy.

All this begs the question how and why CHers are susceptible or predisposed to the CH syndrome.  If you follow the genetotrophic discussion, it is clearly possible it started at conception and following fetal development where there was insufficient maternal vitamin D3 during pregnancy.

There's a second question.  Why is CH one-sided?  The answer here is a simple asymmetry in morphology during fetal development, meaning the two sides of our brain are not mirror images and one side developed with a slightly different trigeminovascular structure.

So there you have it for less than 50 cents, my short and simple working model of the origination and development (pathogenesis) of cluster headache.

As a side note, Tony Only ran a survey of CHers there in Finland.  Over 50% of them had a second headache pathology, usually migraine.  That's amazing as less than 4% of CHers here in the US have a second headache pathology.  However, when you look at a map of Finland and realize half of the country lies north of the Arctic Circle, a chronic vitamin D3 deficiency among Finlanders is an obvious result.  Not enough UVB in direct sunlight to produce the needed cutaneous vitamin D3 and bang - CH at a much higher rate and more CHers with migraines than any other non-Scandinavian country.

Take care,

V/R, Batch