generating questions.
It was difficult for me to condense the information presented by Dr. Clauw which
was a power point type thing... my syllabus does not have text, only power point slide copies.
First off... the main thrust of his lecture was the definition of fibro.
This syndrome is basically an overresponse by the nervous system to sensory and pain stimuli. In a fibro person (who inherits this tendency)...it is like a radio turned up to full volume all the time. In normal people there are feedback loops in the brain to turn DOWN stimuli, after they are perceived. In fibro this does not happen. So ALL stimuli tend to be preceived as noxious.
The facilitator compounds listed:
Quote:
Facilitators in sensory processing + factors are:
Substance P
Glutamate and EAA (I don't recall what EAA is)
Serotonin 5HT2a 3a receptors
Neurotensin (a cytokine)
Nerve Growth factor
CCK (cholecystakinin)
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are in excess in fibro. So Pharma is looking at antagonists to these receptors.
For example a substance P antagonist is in phase II or III trials right now. Its target is depression, but it may prove helpful to fibro patients. I posted this on our Depression forum.
The inhibitor compounds:
Quote:
Inhibiting factors - are:
Decending anti sensory pathways which include
Norepinephrine/Serotonin 5HT1a, b
Opioids (endorphins)
GABA
Cannabanoids
Adenosine
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are being looked at as reducers of fibro symptoms by increasing their activity at receptor level.
The pain loop is a complex circuit of ascending and descending fibers, and is really too complex to go into here.
Now if you look at the Most valuable treatments... gabapentin and Lyrica are listed as primary interventions at this time. Both do NOT affect GABA per se...here is there pharmacology:
Quote:
Mechanism of Action
LYRICA (pregabalin) binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin is unknown, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin’s antinociceptive and antiseizure effects in animal models. in vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function.
While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
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The GABA functions are not primary but peripheral, and still not understood.
I would like to comment to Augoldminer...that some patients over the years on this board and Braintalk, have seen improvement in MS type symptoms and fibro by going on the gluten free diet. Gluten is a primary trigger for autoimmune issues in some patients. Some even do casein and corn elimination diets and find response to those as well.
Autoimmune issues can be triggered by viruses, and vaccines as well.
And they may exist in patients IN ADDITION to fibro..often people have several issues, which may or may not overlap.
Dr. Clauw believes that fibro is a genetically transmitted syndrome, and does not occur in certain people, because they lack the genetic error that allows the pain receptors to go into overdrive. That is his opinion at this time.
L-glutamine is thought to inhance GABA functions, and I have seen Inositol also recommended for this (it improves glucose utilization in the brain).
While Dr. Clauw does not work for drug companies, he did suggest that the combination SSNi and SSRi drugs help more than plain SSRi types. The new drug Milnacipran is very effective with very few side effects now used in other countries. It is very close to FDA approval here and may be available in one year or so.
I will also add that Dr. Clauw said that Fibro is the "last great frontier" that the drug companies are looking towards...
they want to find effective pharma agents because...well, frankly there is a huge financial gain to it. He predicts "blockbuster"
agents in the near future.
Here is the link to the new agent that may help with blocking excess substance P:
http://neurotalk.psychcentral.com/sh...ad.php?t=19026
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All truths are easy to understand once they are discovered; the point is to discover them.-- Galileo Galilei
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Weezie looking at petunias 8.25.2017
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