Amine neurotransmitter CH connection

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Posted by Bobbie P. ( on February 11, 2000 at 22:53:54:

Okay, time to put on your thinking caps, this is going to hurt! Bob P, this latest brain wave involves serotonin so please sharpen your pencil, input on this latest theory would be great. It's probably got holes in it but I have taken it as far as I can at this time(my brain can only handle so much excitement). All constructive comments and criticism welcome. The more we learn about our headaches, the sooner we find the cure! Here goes:

What, if any, are the roles of the amine based neurotransmitters, serotonin, norepinephrine dopamine and the sex hormones in relation to cluster headaches? In response to this query we find that:
- Cluster headaches are usually preceded by mood alterations
- Imitrex has been used with effective results for CH relief
- Correlation between onset of clusters at puberty and or high productive sex hormone years and the dissipation of clusters at menopause and or low productive sex hormone years.
- CH sufferers have above average incidence of:
- Depression
- Chemical dependency i.e.: nicotine, alcohol
- Low testosterone levels (during CH cycle)
- Female hormone imbalances
All of these traits find a relationship with these particular neurotransmitters. If the level of these neurotransmitters are altered, then changes affecting oneís state of alertness, relaxation and mood occur in the body.
Norepinephrine and dopamine are also involved with alertness. An abundance of norepinephrine in the bloodstream causes stimulation of the hypothalamus, which responds with increased levels of LH releasing hormone activity. LH, lutenizing hormone, is produced by the anterior pituitary. It is responsible for causing ovulation and consequently the production of progesterone/estrogen in the female and the production of male sex hormones from the testes. We know from studies that the male cluster subject shows low testosterone levels during a cycle and we have (unsubstantiated) indications that a large percentage of women are cluster free during pregnancy. We also know that a large number of cluster headache sufferers have attested to having diminishing cluster cycles as they get closer to middle age.
*As a note of interest, the enzyme tyrosine plays a major role in the creation of dopamine and norepinephrine.

We know from statistics that low levels of serotonin are associated with depression.
Now, the latest breaking news is the discovery of mutation in the genetic code for the serotonin 5-HT2A receptor (National Post). From what I have been able to understand, this mutation involves abnormally enlarged serotonin receptors. The effect of this mutation would cause a vacuum effect so that too much serotonin would be taken out of the system. (The study was done in relation to suicide tendencies. Serotonin acts to inhibit the brain from acting on certain impulses such as the impulse to commit suicide.) It is interesting to note that the study found that significantly more men showed the mutation than woman did.

- Is there a relationship between these neurotransmitters and our circadian rhythm mechanism? (There is a variety of evidence which suggests that dopamine release is high in light.)

- Does serotonin play a role in inhibiting norepinephrine and dopamine?

- Proposing that the initial area of malfunction causing Cluster Headaches is in the suprachiasmatic nuclei, and assuming that itís function(s) is run on the same negative feedback system as the other functions of the hypothalamus, then what particular chemical messengers are involved in the process?
*If we speculate that serotonin and the other amine neurotransmitters are the key players, then the information regarding the mutation of 5-HT2A takes on significant relevance.

- If there is a correlation, then what is the link that binds these factors together in relation to cluster headaches?

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