Fibromyalgia Community

Also I was reading that Substance P binds to NK-1 receptors, so would NK-1 antagonists maybe show promise in treating fibromyalgia? Everything Ive read relates to emesis from chemo. Have any studies been done with something like Aprepitant for FMers?

Ok, enough 20 Questions Am I making your brain hurt? Sorry. Medical leave of absence = more time = reading = driving Dr.P bonkers with all my questions!! This all fascinates me... maybe I should go back to school.
Kimber <3's chem.

Kimber,

This is an excellent question! I hope that Dr. Pellegrino can give one of his detailed, easy to read, and easy to comprehend masterpieces to answer "all" of your questions.

I have been wanting to ask similar questions, but wasn't sure how to word it! I am curious about the "flow" of messages that ends with "pain everywhere".

Dr. Pellegrino:

Do "all" messages (stress, fatigue, pain, etc.) go to the brain.

Does the brain then "garble" everything up. How?

Do "all" garbled up messeges then go through the DNIC system before being sent to the spinal cord.

With the multiple, constant irritants and a DNIC System that connot tone down pain levels, does the spinal cord then become sensitized. How?

Do the messed up messeges that then leave the spinal cord to nerves throught the body, cause Autonomic Nerve Dysfunction and pain everywhere. How?

Can you correct this very simple summary and explain the whole procress so that it is "much" more comprehendable.

Thanks!

Hi Anon,
This might explain some (not all) of your questions. Its part of the article link i posted above:

"Central sensitization describes changes that occur in the brain in response to repeated nerve stimulation. Following repeated stimulation, levels of neurotransmitters and brain electrical signals change as neurons develop a "memory' for responding to those signals.

Frequent stimulation results in a stronger brain memory, so that the brain will respond more rapidly and effectively when experiencing the same stimulation in the future.

The resulting changes in brain wiring and response are referred to as nerve plasticity (describing the ability of the brain to change easily) or central sensitization. Thus, the brain is activated or sensitized by previous or repeated stimuli to become more excitable."

I'm sure Dr P will give you a thorough explanation of all your questions

Kimber

Kimber,

Your explanation of "central sensitization" is great. Thank you for your reply.

I found this previous discussion on sensitization that has a post from Dr. Pellegrino. Maybe this is why he has not replied to this discussion.


http://forums.webmd.com/3/fibromyalgia-exchange/forum/16252/0?@821.essuav6Ikdq @

FMers.....I have one comment to make here.....after all is said and done.....I think that FM is in our heads.....LOL...as it does have a lot to do with our brain and our nerves also....

I am also interested in this as my daughter has done some of her own research and we are now trying some things....I will let others know once I know exactly how this will affect me....

Take care and I am sure that Dr. P will get back to you on this....


MiMi

Hello!
I am responding to your question from some time ago about "where is everyone from"?
I see you and I are both in Pgh, PA! It is nice to know someone else is in the area? Have you been to any of the support group meetings yet?
Thanks,

From now on, when someone says: "Aw it's all in your head".
I will just say "Yes it is!" and walk away. LOL

For some reason I do not think the Doc will have any additional input. Please post what you and your daughter find or question!

I will, also, put my thoughts together and repost.

Maybe if we all put our messed-up Fibro Brains together, we will be able to come up with something worthwhile. HaHa

Kimber,
I think you should go back to school. I have been out of work and I finally decided to go back to school so I can return to the workforce at a higher pay so I will have the opportunity to work less hours and still bring home enough to get by.
I am loving school more now that I am 33 than I ever did before. If you can do it, then DO it!

Stahl, S. Fibromyalgia—pathways and neurotransmitters. Hum. Psychopharmacol Clin Exp 2009;24:S11-17

Levine J, Reichling D. Fibromyalgia: the nerve of that disease. J Rheumatol 2005;32 Suppl 75:29-37.

Kramer H, He L, Lu B, Birklein F, Sommer C. Increased pain and neurogenic inflammation in mice deficient of
neutral endopeptidase. Neurobiology of Disease 2009;35:177-83.

Vierck C. Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia). Pain 2006;124:242-63.

Price D, Staud R. Neurobiology of Fibromyalgia Syndrome. J Rheumatol 2005;32 Suppl 75:22-28.

Nielsen LA, Henricksson KG. 2007. Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia); the role of central and peripheral sensitization and pain disinhibition. Best Practice & Research. Clinical Rheumatology. 21(3):465-80.

Bradley L. Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia). J Clin Psychiatry 2008;69[Suppl 2>6-13.

Those concern central sensitization in FM. Here is an interesting one on thirst pain:

Farrell M, Egan G, Zamarripa F, Shade R, Blair-West J, Fox P, Denton D. Unique, common, and interacting cortical
correlates of thirst and pain. PNAS 2006;103(7):2416-2421.

Hope this helps.

Hi Kimber,

Sorry for the delay but this is my second attempt to answer your question. The first answer failed to post and was lost. After a few days of "recovering" from that lost effort, I'm trying again!

There's a lot we can do for central sensitization...every FM treatment available works on a nerve "target" to try to decrease pain intensity or improve pain blocking We can't rewire things back to normal, though, at least not yet.

So what are nerve targets? These refer to places in the central nervous system where medicines or other treatments (eg. acupuncture, TNS unit) can activate or inhibit neurobiological responses to control pain. Central sensitization (CS) is the rewired endpoint in FM that reflects both abnormal pain activation and defective pain inhibition: I call this the "double whammy" effect where too much pain forms and too little is blocked.

In FM, the pain activating system becomes oversensitive due to persistent pain triggers leading abnormal responses from neuro-compounds such as substance P and glutamate (too much of these). These compounds increase pain signals leading to wind-up and pain amplification. Along this pathway, different medicines work on different targets such as the sodium channels (eg amitriptyline) or the calcium channels (eg. pregabalin) or the NMDA areas where substance P and glutamate are active (NMDA blockers like ketamine or dextromethorphan). In the brain, dopamine enhancing meds (eg pramipexole) may lessen pain via dopamine targets. And so on....

In FM, the pain inhibitory pathway becomes defective, including the DNIC system, which leads to impaired filtering of pain signals (more pain gets through). 2 main nerve pathways are involved on the inhibitory side, the opioid pathway and the serotonin-norepinephrine pathway. Opioid meds target the opioid pathway; they help improve pain blocking. Likewise, SNRI meds (eg duloxitine, milnacipran) are felt to work by improving the availability of serotonin and norepineprine to inhibit pain. Some meds (eg. tramadol) target two areas (ie. both opiod and seroton-norepi pathways).

The rewired abnormality, ie the CS, affects the brain, brainstem and spinal cord nerves esp. including their autonomic nerves. The treatment goals on a neurobiological level are to reduce pain severity and improve pain blocking which equals less FM pain overall.

Now a question for you, Kimber. I came up with a "nozzled garden hose" analogy to explain CS to people. Can you explain how I came up with that?! Clue: think about the double whammy mechanism.

Dr.P

Dr. Pellegrino,

Thank you so so so much! Awsome post. I should have never doubted, that you would reply with yet another masterpiece!

Dr. P.....now you know that a post would never just disappear around here......not on this site.....LOL...

Interesting post though....my daughter also has chronic pain, which I think I have already told you this....and it is not FM...thank goodness....but she has been doing a lot of research about chronic pain....and she somehow found a questionaire that she wanted me to take....so I did and she decided that I have little or no dopamine.....and that she has something different....so...with this being said....and she is still reading about it....but she did order a supplement for me...and I was amazed...the first night I slept for 8 hours....which I have not done in years now.....I could hardly believe this myself....

When I reported back to her what had happen....she could hardly believe this also....

So my question to you is....this....is it normal for us FMers not to have enough dopamine? And do you know if this has been studied.....she also thinks that the norepherine has something to do with it....so she is still doing the reading about this....

I did want to share this with everyone....now I do find this strange....as I am one of the people who can not take sleeping pills or pain medicine....and it work like it is suppose to....

Thanks again for sharing....


Take care...


MiMi

Mimi,

Mirapex is a newer dopamine antagonist(sp?) drug that is recommended for Fibro patients who suffer from restless leg syndrome for better sleep!

Wow! Eight hours, you make me want to try it.

Hi MiMi,

Posts and thoughts go to the same place when you have FM, huh?!

Dopamine is one of the "Big 3" that's low in FM. The 3 major spinal cord and brain chemicals, serotonin (5-HT), norepinephrine (NE) and dopamine (D) have all been found to be low in FM and depression. All three of these neurotransmitter/hormone chemicals play a role in controlling pain, mood, anxiety, motivation, happiness etc. Regarding our mood, 5-HT can be thought of as the brightness switch on your TV control: less bright means depressed mood. NE is the contrast switch: less contrast means less clarity and focus. D can be the color control; less means less detailed richness in our experiences.[br>
All three are felt to play a role in sleep also. Dr. Holman published a study on dopamine and FM, and the beneficial effect of a specific medicine to increase dopamine levels (called a dopamine agonist). You may have experienced such a beneficial result with the particular med you took.

Hope you have continued success!

Dr. P
[br>