Serotonin is produced primarily in the gastro-intestinal system from tryptophan.  In reviewing Gary's health history today, we noticed that he started having his serious GI problems not too long before he began experiencing CH.  The GI problems got worse, and it was around that time he went chronic.  While he's had ulcers in the past, after numerous endos and colonoscopies, he is diagnosed simply with "GERD" and IBS.

It seems too simple to be probable - but I know for sure that 2 other chronic clusterheads that are non-responsive to meds for the CH have serious problems with GERD.

I'm not proposing the CH is caused by the gastro problems, but what I'm wondering is if the gastro problem(s) is (are) in any way related to problems with serotonin production, affecting the treatment of the CH?  Maybe an inability to properly metabolise the triptans &etc?

????????????????????

Laurie

Just another example of why the doctors have to look at the whole patient , not just treat the symptom.  All the body's systems are interconnected and whether it be seratonin production, testosterone, poor blood flow, neurological damage.....the whole package must be assessed and treated.

Because it hurts so much, we often just are looking for instant pain relief.

Paul

Very good point. Maybe that may have somthing to do with the melatonin working for alot of people maybe there is something there,is melatonin something that produces seratonin?? HMMM. Coach Bill

It's the other way around - but still connected.  Melatonin is produced FROM serotonin:

"The precursor to melatonin is serotonin, a neurotransmitter that itself is derived from the amino acid tryptophan. Within the pineal gland, serotonin is acetylated and then methylated to yield melatonin."

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Laurie

...and Melatonin levels are related to many other adrenal functions, including testosterone:  START PRINTPAGEMultimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or END PRINTPAGE  (posted this link in the thread on testosterone, sorry to be repetitive).

Laurie  :)

To add my 2 cents...

Histamine is produced in large amounts during a CH, producing the red eye, tearing, runny and stuffy nose, etc.  Another effect of Histamine is to stimulate gastric juices (acid).

Ray

Garys_Girl wrote on Nov 29^th, 2008 at 6:16pm:

It seems too simple to be probable - but I know for sure that 2 other chronic clusterheads that are non-responsive to meds for the CH have serious problems with GERD. Laurie

 I dont know if you were counting me but I am a chronic clusterhead that is non-responsive to most meds,  I have numorus GI problems that lead to the removal of about half my stomach.  After my stomach surgery I became chronic! :-?
 But I really dont have an answer for your questions,  I am just adding my two cents. 8-)
   Hang in there Laurie and keep up the good work,
                                        Phil 8-)

I am reluctant to post to this because I don’t believe I fit the case scenario.

I am a daily chronic 1-4 per day for 5 yrs straight.

What works for me (lithium and O2) what don’t work (everything else).

I had an H-pylori (sp?) infection type ulcer 11 yrs ago and CH crept in 6? yrs ago.

My understanding is that O2 is believed to cause the brain to secrete serotonin quicker during O2 therapy. This is why we chronics push the O2. if I used Trex for every hit, we would need a preverbal gal a month supply.

I have also noted that many of the drugs used for this (serotonin boosters and regulators) are more effective on woman than men making them far less useful to the majority of sufferers (men).

Many of the drugs tried on me nearly caused me to meet my maker, and were promptly ruled out as beneficial in any way. I just don’t want people to go running to the doc because they read the info posted here for a round of unnecessary mood stabilizers.

I have also noted that many men loose the beast later in life when testosterone levels drop way off so there is a lot of wiggle room on this one.

Add; I guess being chronic has also made me skeptical and pessimistic in nature so pardon me for putting a little bit of vent in there!

PFW’s to all!! [smiley=sayyes.gif]

Roland. ;)

I'm tired right now, so I'll just post my most 'recent' stomach issue, before the CH.

Okay, so, my Gallbladder started acting up 3 years ago in July.

I suffered with it for 2 and a half years, it was removed on January 4th. I had 7 HIDA scans in that period, all were normal, but each one made the symptoms worse. Took them going in and removing it to find the damned thing covered in adhesions.

Though, I am on Nexium, for my vocal chord dysfunction and have IBS with constipation now.

This is an interesting theory. I've had acid reflux for years (before CH). Most of the time I wait for it to get really bad before I get back on the nice little purple pills and then take them till it clears up for a while and get off them again (did I mention I hate to take pills?). I've never paid attention to how the headaches hit when the indigestion is really bad, but will now.

I'm on the little purple pills now and am in a low cycle right now. Ummmmm......

Hugs BD

Barb, we don't actually see a relationship between the GERD/IBS and the cluster activity.  (Gary's situation is so bad they've got him on 40mg of Protonix 2x a day.  There are days he'll only take 1, but he hasn't been off of it for - 2 years now?)  ...It's just that he's chronic with no pain free time at all, and the clusters have been non-responsive to all meds, be they abortive or preventative.  

What I'm wondering is to what extent the ability to properly metabolize stuff is at play here (though that wouldn't explain why stuff you snort or IM don't work either).  

But I'd love to hear back what you experience!

Laurie

wrote on Nov 29^th, 2008 at 9:45pm:

Garys_Girl wrote on Nov 29th, 2008 at 6:16pm: It seems too simple to be probable - but I know for sure that 2 other chronic clusterheads that are non-responsive to meds for the CH have serious problems with GERD. Laurie  I dont know if you were counting me but I am a chronic clusterhead that is non-responsive to most meds,  I have numorus GI problems that lead to the removal of about half my stomach.  After my stomach surgery I became chronic! :-?  But I really dont have an answer for your questions,  I am just adding my two cents. 8-)    Hang in there Laurie and keep up the good work,                                         Phil 8-)

Phil, if you told me that, I'm so sorry, I didn't remember it.  So let's make that 3 now.  

And Ray - that's very interesting about the histamine and gastric juices!  I didn't know that.

Wish I had the money to quit my job, get proper biochemistry training, and research this stuff full time!

Laurie

I am chronic from outset and pretty resistant to standard therapy, although alternative has been pretty good.  I have had bad GERD for awhile, but we have always connected it to asthma and allergies.  Maybe the histamine connection like Ray said (extra histamines in my system...from allergies OR CH) producing too much acid), but there is also a nerve that makes both the esophogus and lungs hyperreactive...at any rate 70% of GERD cases have asthma too.  
Very interesting though.  
Lisa

Gary responded to alternative therapy at first too (not seeds, but shrooms) - but the mechanism of action of alternatives is quite different than the traditional meds.  I guess I should also be asking the people who have gone the alternative route because they gave up on traditional meds about their issues with GERD or other gastro-intestinal problems!

Laurie

Just to throw the cat among the pigeons
I’ve been chronic since late 2004; prior to that I only had one cycle 5 years earlier, never had gastric problems, got CH late in life at 49 now 59.

I never went the so called traditional meds preferring o2 to abort & then started experimenting with Taurine, Magnesium & Calcium supplements & have had some reasonably good success.
Prior to starting the supplements the biggest break I would have between hits would be no more than a couple of days.

Exert from my CH diary:
April 14, 2006 Started Taurine & Magnesium supplements.

Low cycle October 2, 2006 till June 20, 2007 Start of the biggest PF break since going chronic, this lasted 261 days.

High cycle lasted from June 20, 2007 to August 9, 2007, 50 days.

Low cycle lasted from August 9, 2007 to June1 2008, 297 days.

High cycle lasted from June1 2008 to July 24 2008, 53 days.

Current low cycle July 24 2008 to this date Dec 1 2008, 130days with fingers crossed.

Maybe Gary should try this regime after talking it over with his GP, there’s nothing to loose.

Cheers
Barry

I am (or was) a med-resistant chronic with some gastric problems. I can't digest meat well, but changing my diet to 80% fruit and eliminating meat did not change anything regarding the headaches. The attacks lasted non-stop for a year, except for the short bouts of 40mg Prednisolon per day.

Rather what has worked 100% has been 90mg etoricoxib (Arcoxia) daily. It's not a common CH med, but rather a very inflammation-specific long-acting NSAID. Doctors would not have tried it, I suggested it to them myself. Now I'm attack and headache-free.

I tried oxygen, Verapamil, Depakote/Deprakine, Topamax, Lyrica and triptans previously. None of them helped, except Zomig Nasal only once. Indomethacin worked for a small while, but not after that.

First I tried meloxicam (Mobic) 15mg daily, which my mom loaned to me. It's also a long-acting NSAID, but not as inflammation-specific as etoricoxib. It was immediately effective and stopped the attacks like to a wall, like Prednisolon did. After a couple of weeks it began to stop working, as in I began getting attacks again, but since that I've been taking Arcoxia. No attacks, no pain!

I urge all of you, who get or used to get any help from Prednisolon, to at least try Arcoxia. I visited three neurologists and they all thought that I would have CH. Now they are saying that I still probably have CH, but in clinical practise and in theory the CHs behave differently. A lot of different kinds of medical problems and their treatments, like mine, remain undocumented and unpublished in medical literature.

- Best regards and PFDAN,
Rosa

Serotonin is definitely strongly present in the gastrointestinal tract. Here is a very interesting page about the whole thing: START PRINTPAGEMultimedia File Viewing and Clickable Links are available for Registered Members only!!  You need to or END PRINTPAGE

Some highlights:

"Serotonin is found in many tissues:

   * In the digestive tract which contains about 95% of the total amount of serotonin of the body, localized in enterochromaffin cells. "

From a related wikipedia page:
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"Enterochromaffin (EC) cells (Kulchitsky cells) are a type of enteroendocrine cell[1] occurring in the epithelia lining the lumen of the gastrointestinal tract. They produce and contain about 90% of the body's store of serotonin (5-HT)."

Again from the first page:

"Serotonin or 5-hydroxytryptamine is synthesized from L-tryptophan. The quantity of tryptophan ingested daily is about 0.5 to 1g; the recommended daily allowance is about 200 mg, of which only a small part is converted into serotonin."

"Transformation of tryptophan into serotonin involves two steps:

  1. Hydroxylation in 5-hydroxytryptophan catalyzed by tryptophan hydroxylase, which is the rate limiting enzyme of the synthesis. This enzyme requires for its activity the presence of tetrahydrobiopterine, oxygen, NADPH2 and a metal, iron or copper.
  2. Decarboxylation of 5-hydroxytryptophan is catalyzed by L-aromatic amino acid decarboxylase with pyridoxal-phosphate as coenzyme."

So the presence of oxygen is one requirement of the enzyme which produces serotonin. Could this be one key as to why oxygen works so well for some?

"In the brain, serotonin biosynthesis depends on the quantity of tryptophan which crosses the blood-brain barrier. Only free plasma tryptophan, i.e. unbound to albumin, penetrates into the brain; decrease of its free ratio reduces its penetration. Moreover, other amino acids are in competition with free tryptophan and limit its entry in the brain. Plasma cortisol, whose level is increased in depressed patients, decreases free L-tyrosine and free L-tryptophan concentrations in plasma, i.e. the forms which penetrate into the brain. Insulin, of which secretion is increased by carbohydrates, has an opposite effect and decreases the concentration of the amino acids other than tryptophan."

I think it's very interesting that the more you have cortisol in your blood, the less you have serotonin in your brain. Yet cortisol (=corticosteroids) seems to be of much help to many of us.

Any of you have any experience of using insulin with CH?

Also:

"Transformation of serotonin into melatonin, which should not be regarded as a degradation pathway because melatonin is also active, is carried out primarily in the pineal gland. It involves two steps:

  1. Acetylation of the amine group by N-acetyl transferase leading to N-acetyl-serotonin.
  2. Methylation of the OH group by 5- hydroxyindole-O-methyltransferase catalyzing the transfer of a methyl group from S-adenosyl-methionine to obtain acetyl-5-methoxytryptamine or melatonin.

The concentration of melatonin in the pineal gland presents circadian variations: it follows the variations of N-acetyl transferase activity, increasing during the night and decreasing during the day, darkness and light playing a regulatory role via catecholamines. Light inhibits melatonin biosynthesis. "

I've previously written somewhere here about this as well. One mechanism as to why the nights are more difficult for some of us might be that as the body makes melatonin from the available serotonin, the amount of serotonin is decreased. When you take melatonin before going to bed, the body will take notice of this and not convert as much serotonin to melatonin then. More serotonin = less pain, because the serotonin is a very powerful vasoconstrictor.

Also it's important to remember that the release of serotonin from the raphe-nuclei in the brain is vastly decreased during sleep and almost stopped during REM-sleep. This would explain why REM-sleep is very bad for some of us.

- Best regards and PFDAN,
Rosa

Rosa, thank you so much for the more detailed info!

Unfortunately, prednisone taper (or dexamethasone, which he had to use when he had pneumonia last year) didn't affect the CH activity at all.

Barry, another unfortunately - taurine increases bile production, so people with GERD will have trouble with it.  One of the potential side effects of taurine is peptic ulcers (and for those with IBS it could also be a problem because it can also cause diarrhea).

He is on a 2:1 Mag:Cal supplement and takes a multivitamin.  But perhaps we should consider taurine in lower doses.

Interestingly, taurine is an "inhibitory neurotransmitter" and has been used as an anti-epileptic.  (Many of the traditional CH meds are antiepileptics:  Topomax, Gabapentin, Depakote, etc.).  Notably, ALL are very hard on the stomachs of people with GI problems.  Gary couldn't tolerate the Depakote.

Laurie

Laurie, keep up the good work!

I think you're doing well for trying to think outside the box. The fact that Gary doesn't seem to respond to normal CH meds doesn't necessarily mean that he doesn't have CH, but might instead mean that he has CH-like symptoms because of a different mechanism. Finding that mechanism is the key to pain-free time.

Best of luck to you in your quest!

- Rosa