neuropathy and WED

[peanut1]

My doctor told me a theory out there is that neuropathy can kick WED into severe even after the neuropathy has healed or supposedly cured. I personally find this intriguing as when the neuropathy pain started was when the WED/RLS was rapidly getting worse. After the damaged nerve supposedly healed the WED did not return to it's previous state. I'm wondering if something switched the WED into severe and would like to learn more about this theory. I also know that the nerve pain acts up if I do certain things so it's possible it never REALLY healed. Curious to know what others think.

[figflower]

Hi Peanut. A while back I did some research on how iron, dopamine, dopamine receptors, the central nervous system (brain, spine) and the peripheral nervous system come into play in terms of RLS. Let's start with what I believe (and researchers too) is going on. What's going on is a genetic predisposition to RLS. I think most, maybe all of us, have low levels of brain (not so much body) iron and that lack of iron causes our dopamine receptors to be small, few and pathetic. The receptors hurl dopamine, a neurotransmitter, down our spines (CNS) to our arms and legs (aka peripheral nervous system) and quiets them. The dopamine bounces its way from neuron to neuron along our spines on its voyage to the peripheral nervous system. I think for most of the people on earth, their dopamine shoots out of their receptors in a stream. For us it's a dribble. And maybe, just maybe, that dribble is enough to quiet our arms and legs. But one bump in the road, such as a spinal injury (anywhere from neck to coccyx) can trigger or worsen RLS. And you're right, even after our backs, or compressed nerves, feel better, they may no longer provide as good a route through which the dopamine must travel. Fear not, because we can always look upstream, and try to shore up our shoddy dopamine receptors and try to get a stream going . Let's face it, the vast majority of people with back and nerve problems will never develop RLS. But those of us genetically pre-disposed to it will. So we gotta get a stream going!!! So we take upstream drugs such as dopamine agonists or pain killers and that's fine but I am looking for other ways to squeeze more dopamine out of those receptors or shore up the receptors...preferably.

I know that the iron bis-glycinate (aka Ferrochel) does not provide you with complete relief, but it does me. But I have to take it during an attack, on an empty stomach. If I take it in the morning it will do nothing for my evening attack of RLS. And if I take the iron with any other substance such as magnesium or calcium or milk it negates the effect all together. And if I take any form of iron other than iron bis-glycinate it will not work. One tablet provides one night of relief, for me. I wish it did the same for you. So from what I understand, iron will actually shore up our receptors. Iron is not a dopamine agonist, I do not believe. I believe that potassium (the right kind, in the right amount) will act as a short lived dopamine agonist. So will quinine and maybe tumeric. But I'm not in the market for a dopamine agonist, I believe even the natural ones can potentially down-regulate our already down-regulated receptors. I want to shore up my shoddy receptors with something totally natural and healthy. I do not particularly like iron, especially since I already have the red blood count of a healthy 18 year old man and the ferritin stores of Hercules. Iron is my emergency med when all else fails. Clearly, MY brain cannot call up that much needed iron from my stores so why bother adding to them, but when that chelated iron is circulating in my bloodstream, unbound, my brain sucks its up and provides relief. But by the dawns early light that iron is stored and I must repeat the process with my next attack. To contradict myself here, for all I know, my healthy iron stores IS helping in some way because I only get an attack (as opposed to those who have it 24/7/365) it seems when I take Tagamet or Benedryl or over-eat at night. OMG, if I so much as look at Melatonin I get not only restless legs but restless body. It's insane what it does to me. I took HRT for a while and that made my legs crazy too. I've heard a lot of people react the same way to the SSRIs and even statins. I think even splenda can trigger an attack for me. When I was younger these substances did not bother my RLS nearly as much but as we age so do our receptors. Everyone's receptors do but somehow it doesn't much matter to the rest of the world. It is only we who are pre-disposed to RLS that can't afford that age-related decrease in receptors.

My plan in improving the RLS and my overall health is to first eradicate my candida overload and to try to consistently under-eat. According to drug addiction websites, under-eating or intermittent fasting will up-regulate our receptors and that's very good for us. Ipso facto, over-eating will down-regulate our receptors, that's bad, very bad. I'm an over-eater, so I have my work cut out for me. I also believe that there might be something to magnesium. I think magnesium is a dopamine antagonist so at first it might not work or even make RLS worse but then in the long run it might up-regulate our receptors. Once again, if dopamine agonists down-regulate our receptors then dopamine antagonists should up-regulate???? So maybe a dopamine antagonist in the morning will mean a better night's sleep? Just a theory as to why magnesium seems to help so many people. Taurine too.

Hope that helps some.

[debbluebird]

You have stated some very interesting theories. How are you going to eradicate the candida ? Also the under eating is interesting. What will be the dopamine antagonist ? Is it the magnesium.
Thanks

[figflower]

Hi DB! Hope u r well? Magnesium is fascinating to me. I read an article that stated that magnesium is needed for the production of dopamine. That's great but supposedly we with RLS have plenty of dopamine kicking around up there. We need to get that dopamine down our spinal column and to our arms and legs. It's the receptors that release that dopamine from our brains. BUT then I read an article that stated that magnesium INHIBITS the release of dopamine. So why should it help so many people? Substances that inhibit the release of dopamine are antagonists...right? And antagonists should technically up- regulate our receptors. Magnesium may also help because it is supposed to be good for nerves in general. It is also supposed to make u go more. Maybe for some, not being constipated via magnesium is helping their RLS

Candida u ask. I could write a book. Gotta make dinner right now. Will post cliff notes on Candida later tonight. Is your tongue coated?

[debbluebird]

Well, I do have candida. Tongue is coated, as well as other symptoms. I looked it up. So how much is this related to RLS ? I did look that up too and found some instances.

[figflower]

Candida, what can one say, it is a formidable foe. I will be fighting it for the rest of my natural life and probably part of my unnatural life. I call it the yeast monster. When it's in it's single celled, non-pathogenic form, it is a welcome inhabitant in our gut microbiome and it is my understanding that most people have it...in it's friendly form that is. But give it an inch and it takes a whole city block. I have no idea when it began for me, could have been when I was very young, but I know when I was 35ish my IBS was out of control, so was my fatigue and I felt like I was being poisoned. My GI doctor offered me this cinnamon flavored Metamucil wafer, new on the market he said. I told him I was dying and he shrugged. My new-age allergist who I had been seeing since 19 years of age and always loved told me I had a yeast overgrowth and then me (little miss know it all), said "no way, I never get yeast (vaginal infections) how could it be over-growing in my GI tract." Well he talked me into having the antibody test. VERY high values. I had to go on a sugar free, yeast free (no longer believe that's necessary) diet for two weeks before he would give me the prescription antifungal called Nystatin. Within two weeks on the diet I felt some relief and then within two months of taking the antifungal I was much better and back to baseline IBS and baseline fatigue.

It kept coming back and I kept going back on the Nystatin. I knew it was back because I would get to the point where nothing agreed with me, not even a celery stick. And then after a couple of months on the Nystatin it seemed like everything agreed. My research into Candida was limited to the book "The Yeast Connection" until the advent of the internet, followed by the explosion of research into the gut microbiome. Micro-organisms want to live every bit as much as we do, maybe more. They form cities, called bio-films, with channels for carrying nutrients into the tribe and for carrying waste away. There's even slacker bacteria in the biofilm that don't seem to work very hard. These bio-films have become impenetrable in many instances, shrouding themselves in a mucous like coating that antibiotics can't penetrate and hence can't reach the little critters. Anyways, I believe that my resident candida got out of control because of my slow motility (aka IBS) and constantly low body temperature. People who are "gut microbiome zealots" believe that our resident micro-organisms are pulling ALL of the strings in our bodies and they would say that the candida is slowing down my motility and lowering my body temperature. And I am quickly becoming a convert.

Back to the Candida, though sugar is probably it's favorite food, don't kid yourself, it will take any nutrient it can get it's claws on. And forget the alkaline diet, Candida's favorite environment is an alkaline one, and a cold one. A body temperature of 98.6 is exactly the point at which candida starts to return to it's single celled form, according to research. Even when the going get's rough the candida will run and hide and wait for better times and then spring back into action growing claws and attaching itself to the lining of my small intestine and sucking nutrients out of my blood stream while giving off waste that is toxic to me. I have invested in an arsenal of natural substances that are supposed to be bio-film busters although I've read that even plain old Mucinex (you know the cold remedy) will do the trick. Once its slimy film is busted then the Nystatin supposedly works much better, as well as things like Oregano oil, thyme oil, colloidial silver - the list of antifungals is endless. But supposedly these substances, even with a sugar free diet, will take forever to work unless you take the bio-film busters. And even if the diet and anti-fungals alone seem to work, it won't last. From what I've read you basically have to pulverize it to eradicate it. I'm pulverizing it, and as usual my digestion is better, and the fatigue as well, but it's far from eradicated as my morning tongue seems to tell me.

I have no idea if there is a connection between RLS and Candida. My instincts say yes. Get the Candida under control and the RLS will improve. I have no articles to back up my instincts. My instincts also say that not only can the Candida trigger or worsen RLS but any out of control micro-organism or even just a naughty gut-microbiome that is not playing nice with its host can possibly be a trigger. People mistakenly believe that if they don't have stomach aches then their gut-microbiome can't possibly be the cause of their migraines, fatigue, allergies, heart disease, obesity, Parkinson's or RLS. Science is proving otherwise

[debbluebird]

I have been researching this all evening. I found where it is related to RLS. I have decided to start eliminating the foods that cause candida. Secondly after a few days I am going to start the intermediate fasting. I really want to see if it will make a difference. Everything on the do not eat list is everything I eat and crave. I know this won't be easy, but when it comes to RLS, I'm willing to do anything. Also, I need to lose weight for many reasons. My gut is not as bad as yours, I have other issues.

[figflower]

The Candida is a bully. Get tough. Be strong, keep exploring. Keep me posted. We will get through this.

[badnights]

I need to clear this up. Receptors receive. They do not send, they accept. They are molecules built into the cell wall eg. into a neuron wall (neurons are a type of cell), that bind to a specific type of neurotransmitter, hormone, or other molecule. Receptors are specific, that is, each receptor type will only bind to a specific type of molecule. The binding causes a response in the cell, either activating or inhibiting a specific biochemical reaction. The molecule is then either released back into the synapse (the space between neurons) or brought into the cell it is attached to, where various things might happen to it, and the receptor is often dismantled as part of this process.

But the point is, receptors receive, they do not transmit. They do not release dopamine or any other molecule. They accept dopamine or whatever neurotransmitter or hormone or drug, and move it into the cell, where something happens as a result (if enough receptors have been activated) eg. an electrical impulse travels down the neuron.

And just for completeness:
The number of receptors in a cell wall changes in response to the chemical environment of the cell. This is called up-regulation if the number of receptors increases, and down-regulation if it decreases. If we have lots of dopamine floating around our synapses in a certain part of the body, it binds to all the available receptors. If these are dismantled as part of the process, and building of new receptors can't keep up, there will eventually be less receptors available (downregulation). In effect, this compensates for the overabundance of dopamine. If there is very little dopamine, the opposite happens: receptor construction outpaces dismantling, and the number of receptors available increases (up-regulation). Other factors come into play than receptor dismantling due to binding, but that's a simple example that illustrates the feedback control.

A dopamine antagonist interferes with the action of dopamine. It can interfere by binding to dopamine receptors without eliciting the response that dopamine would have, while blocking the receptor from binding to dopamine. Other dopamine antagonists interfere with dopamine directly, or interfere with its production. The effect of an antagonist that binds to receptors is often to stimulate creation of more receptors, at least initially, but not always.

A dopamine agonist enhances the action of dopamine. eg, a particular agonist might imitate dopamine by binding to dopamine receptors and eliciting the same response dopamine would have. Pramipexole and ropinirole are our favorite examples.

[badnights]

Figs: there is an enxymatic biofilm breaker called Biofilm Defense by Kirkman Labs. Kind of expensive but I used it in combination with "natural" antimicrobials and the whole treatment was effective. Until it all came back, but that's another story.

[figflower]

Yes, I like your description of the activity of dopamine, dopamine receptors (mainly D2 receptors, right), stimulation thereof, resulting impulses (not quite chemical, not quite electrical). But your story ends there? What about Peanut's question? What about all of the people who don't understand why their RLS got so bad or was triggered just because they injured their back or even later when they had back surgery. Questions like that shouldn't even exist anymore. We know what causes colds and the cascade of events that happen when we become infected with a virus. We know what happens when we who are predisposed to RLS injure our spines, or as we age or when we go through menopause. It's all about getting that dopamine/neurotransmitter to our arms and legs. Just as we have to help our bodies fight that infection when we get a cold, we have to help our bodies build those receptors and shuttle that dopamine to our arms and legs, uninterrupted. It's complicated, yet simple, kind of the way a cold is. Which we still don't have a cure for. You understand what's going on from a very scientific point. Throw these people a lifeline. Instead of an army of zombies there could be an army of people trying to get their backs in better shape, lowering inflammation, dieting, exercise, iron, improving gut microbiome. As DebbieBlue is now doing.

Do you disagree with my description of what is transpiring in terms of RLS and the big picture?

[Rustsmith]

Figflower, current research is starting to find that RLS is so much more complicated than simply iron and dopamine. Johns Hopkins's research appears to be implicating glutamate issues as being responsible for the insomnia problems that can occur even when a DA has control over the urge to move problems. And then there was a paper early this summer that ties histamine transmitters in the brain to RLS.

So, there is so very much that even the experts still do not understand about what causes our problems. Which is probably what we see reports where some people are helped by one class of drug and not another and also why some of us have one set of symptoms and not others.

[figflower]

Yes, and they are finding out ever more about viruses. Despite all that they discover about viruses and how our bodies react to them, it's still in all likelihood the cause of colds or cold symptoms. And lousy dopamine receptors are in all likelihood the cause of RLS or RLS symptoms just as low levels of dopamine cause Parkinson's disease or the symptoms of Parkinson's. How a person contracts a virus is questionable and how our dopamine receptors got to be lousy in the first place is questionable, and the same for Parkinson's, but what's the point of confusing people. The point is, and the reason I responded to Peanut, or anyone, is to take the wind out of RLS' sails. RLS is not the great and powerful Oz, it's just a simple man behind a simple curtain. No magic no mystery. And rather than someone feeling scared or hopeless or confused when their RLS worsens due to an injured nerve I think understanding that it's just a bump in the road on their journey to wellness and not beyond repair is something worthy of knowing.

Sorry to disagree, but I feel that we know just as much (or just as little ) about how RLS works as we do the common cold or arthritis or diabetes or ALS or MS. "Fear is the greatest darkness." If you take the fear factor out of RLS (or any disease) and arm a person with at least a rudimentary understanding of what's taking place in their bodies then they can spring into action. They can take that first step in healing. They can see a pattern emerging. That ah ha moment when someone reads about how antihistamines make RLS worse and they realize that their RLS has not permanently taken a turn for the worse that it's merely the antihistamines. With that little bit of knowledge about dopamine having to travel the whole length of the spine they can discover hidden triggers or soothing substances. But first, someone has to turn the light on for them.

Should I not have provided this explanation to Peanut?

[figflower]

Steve, by the way, I think ultimately we all have to go in the direction you're going in. We have to look beyond our legs and brains and dopamine receptors and iron and question EVERYTHING. Let's assume for now that we with RLS do have low levels of brain iron and resultant bad receptors. I, for one, refuse to believe, that that is the beginning and end of the story. And so do the researchers, and so obviously do you. I, for one (actually there are quite a few people), think that our low levels of brain iron (if such a state does exist in our brains) is caused by our guts, actually our gut microbes. And our bodies reaction to those microbes. I think it's possible that our bodies have clamped down on iron (meaning none gets into our bloodstream from food and none gets released from our stores) because our bodies sense "infection" when it's just our resident microbiome. A microbiome that we can't live without. Can't live with it, can't live without it We think of cancer as being a secondary cause of RLS, as well as rheumatoid arthritis and kidney disease. Is it the disease that is the secondary cause or our bodies withholding of iron in the face of these diseases that cause RLS? Our bodies withhold iron when faced with cancer. So, is it secondary RLS or just regular old singular RLS that is triggered by these things because the RLS susceptible brain can't afford that further reduction in iron? Not everyone with cancer, arthritis and kidney disease will develop RLS? Like everything else to me it's clue. But getting back to the gut microbiome, maybe rather than bad genes when we're born, it's a bad gut microbiome or some combination thereof? Maybe our brains are low on iron because our bodies are always on "orange alert." There's always some amount of withholding of iron going on because of our rowdy microbes. Add cancer to the mix and our bodies go on red alert and then our brains are really low on iron. Maybe instead of donating our brains to science after we die we should just drop ship a fecal sample to researchers right now? In short, I totally agree with you and scientists that there is more to RLS than meets the eye. But isn't that true with every single illness out there? Did you ever think you would see the day when scientists are doing fecal transplants on autistic children? What the heck does the colon have to do with autism? So yes, absolutely, glutamine and histamine could play a huge role in RLS for all we know. But you have to crawl before you can walk, I think. And I think most of with RLS need to understand what science has discovered about RLS thus far. Thus far it's dopamine receptors and getting dopamine down the spine (CNS) and to our limbs to quiet them. I read one unscientific article about the possibility of injecting dopamine right into the spine, almost in a fashion similar to a morphine pump. Which reminds me, I should probably google that and see whatever became of that idea.

[Rustsmith]

Figflower, in my professional work my recognized technical expertise has to do with a specific series of chemical reactions. Both my students and my consulting clients are always asking me questions that involve how the system reacts by changing one input value. So they want to know and their concepts of the system are that if I change A, then B will happen which results in C. With RLS, this would be like if I take a low level DA, then my symptoms are resolved. Sometimes this works well, but only if dopamine was the key input that was controlling the overall system. The problem is that I do not believe that either my chemical system or RLS are a simple linear A to B to C reaction. Instead, it is more like a spider web. If you adjust or improve one thread of the web, sometimes you get improvement and other times not. It depends upon whether that thread was critical to the overall reactions. And, even if you do improve that thread, this just shifts the control of the system over to another thread.

In RLS, I see the neurotransmitters such as dopamine, glutamate and histamine and step B (or maybe even C or D) in my linear model. There are other things upstream of them such as iron availability in the brain as well as other metals such as magnesium, potassium and maybe even sodium. Returning to the spider web, the critical step might be transfer of these metals across the blood brain barrier for some (which might be the issue for some genetics and certainly would be related for secondary RLS where the iron levels in the blood are compromised). For these people, treating to increase ferritin in the blood stream or taking magnesium may help. For others, maybe the issue is adsorption in the gut of the metals or some other chemical that is critical to the proper formation of one of the neurotransmitters.

If you look at RLS at this higher level, then you can start to see how a person with mild RLS might be able to "fix" it by using some form of magnesium if that was the critical contributor for them, but another person would find mag completely ineffective. It also would explain why supplementing dopamine levels addresses one part of RLS, but for some many of us it does not address our sleep problems.

What all this means is that I believe that we concentrate too much on dopamine because it has the most easily measurable response. The researchers are starting to get an idea of the roles of some of the other neurotransmitters and their roles in RLS. But the big question may ultimately be, what is it that is pushing our levels of these neurotransmitters out of whack as compared to normal human levels. For some it may be iron transfer across the blood brain barrier, for others it may be another mineral and for others it may simply be one where the concentrations of the critical mineral (iron, mag, potassium, ...) in the blood are simply being held too low. In each case, attacking the disease by treating in the middle of the reaction (step B in my linear sequence) with dopamine or glutamate may help with the overall symptoms for most, but finding a way to fix the critical mineral or other neurotransmitter precursor (step A in my sequence) could ultimately be the way to go.

This also explains the statement that we frequently make on the board of "everyone's different". This may be because your critical spiderweb thread has to do with potassium adsorption in the gut while mine my be an inability to transfer adequate levels of iron across the blood-brain barrier. In that example, you might be able to resolve your symptoms by eating too much potassium but I would not get relief by increasing the ferritin levels in my blood because the critical step is not the iron levels but a road block of iron transfer that is probably due to genetics.

I realize that I have rambled a bit here trying to describe something that is quite complex. Trying to describe how all this might work without being able to use graphics (and the ability to wave my hands a lot) is rather difficult. Hopefully it is somewhat understandable.