Role of Dopamine and Brain Iron stores

[Edengirl58]

How is it known/thought that dopamine plays a role in RLS? So, is there a test for this or research to confirm scientifically that it is playing a role?

Also, how is it known/ thought that brain iron stores play a role?

[LotteM]

A brief reply from the top of my head. I think they found out initially "by chance" that dopamine agonists work very well (initially!!) for RLS. In earlier guidelines, it was even mentioned that a short course of a dopamine agonist could be used to confirm tue disgnosis: of it took away the symptoms, it is RLS; if not, no RLS.

Since there has been quite some research on brains (of deceased people with and without RLS, but also with neurobiological techniques- don't ask for specifics). That research revealed that dopamine transport to motor cells (activating mainly legs) in people with RLS is hampered. There is an overload of dopamine in the neurons (brain cells) early on in the chain of cells that transfer muscle activating symptoms. This has led to the hypothesis of too few dopamine receptors on the receiving cells. To build these dopamine receptors iron is crucial, and this might explain the already long standing knowledge that many people with RLS benefit from iron.

Other than a short course of dopamine agonists (which is not even an acknowledged test), there is no test for RLS. Not is there a biomarker. RLS is diagnosed through its symptoms (mainly urge to move) and excluding other ailments or medicines that elicit RLS(-like) symptoms. See rls-uk.org and rls.org

This is not 100% correct and far from complete as the neurological system is extremely complex (e.g. feedback mechanisms) and also redundant in that there are many alternative routes. And the neurological system is tightly bound to and influenced by -and vice versa- the hormonal and immunological systems. At least.

[Edengirl58 in reply to LotteM]

I’m really interested in this because I’ve recently used Mind and Body (Psychophysiologic) techniques really successfully to treat my long covid ( I had 15 symptoms for 20 months, was very debilitated and most symptoms disappeared within a few days). I asked the Mind and Body practitioner whose techniques I used whether he would consider RLS as being a Mind and Body syndrome, and he has responded to say that it most definitely is.

However, part of the definition of a Mind and Body syndrome is that there is no ‘structural’ cause for that condition in the body- so RLS would fit, in that there are no bio markers and diagnosis is made solely on the basis of us reporting our symptoms. Hence why I’m interested in what is actually known scientifically about iron and dopamine in people with RLS . Could the remarkable initial effectiveness of (the dreaded) dopamine agonists, and effectiveness of iron infusions be down to a strong placebo effect reducing stress levels, and then that reducing RLS symptoms- similarly Gabapentin having a calming effect?

I am prescribed Gabapentin, which seems to help, and had an iron infusion 12 months ago-after which I had RLS symptoms at all for one month, but maybe this was due to placebo/calming effect? The other strands which make me wonder is the fact that we all have vastly different’triggers’ eg caffeine/ no caffeine, hot water/cold water etc, and vastly different experiences with medication, and then periods where we do or don’t get symptoms. These would tally with the idea of a psychophysiological illness ie one in which the neural circuits in the brain create and maintain these hellishly real sensations in the body.

Thank you for reading - I’d be really interested in any thoughts on the above.

[LotteM in reply to Edengirl58]

There is definitely a cause for RLS. The problem is that for looking at that cause one has to look in the brain and its processes. And that is not so easy without killing the patient first.! And no, in my opinion and I think the RLS researchers would agree, RLS is not a Mind Body Syndrome. I think the practitioner doesn't know much about RLS and the scientific literature about it. He is not alone. RLS is too easily dismissed by too many medical pactitioners. Unfortunately.

[Baz33 in reply to Edengirl58]

Absolutely no to mind body syndrome....

[Hidden in reply to Edengirl58]

I had always entertained the thought that my PLMD/ RLS might be psychosomatic in origin. However, when my son was diagnosed with the same at 12 months of age, I quickly disabused myself of the notion.

[SueJohnson]

This probably doesn't directly answer your question - I don't have time to read it right now but certainly establishes that iron is needed sciencedirect.com/science/a...

[Joolsg]

ncbi.nlm.nih.gov/pmc/articl...

Lots of research is still needed. Iron certainly helps many people, but not everyone. If we could leave our brains to research this in the UK, it would help find the causes. So far, as RLS isn't even taught in the UK, that is unlikely.

[SueJohnson in reply to Joolsg]

You can in the US - rls.org is always asking for that.

[Joolsg in reply to SueJohnson]

I know, it's fantastic. It shows how far behind we are here in the UK.😔

[SueJohnson]

I agree with the others. RLS is not a psychological condition and the effectiveness of medicines and iron is not a placebo effect.

[Edengirl58 in reply to SueJohnson]

Thank you all so much for your thoughts. I am very much in two minds about this. I think my extraordinary experience with long covid where I had luckily no organ damage but extreme symptoms has made me wonder. So I will keep an open mind and see if the Mind Body strategies can help with this cruel illness. I’ll let you know how I get on.

[Munroist]

I had RLS and PLMD symptoms long before I'd ever heard of RLS and I suspect that's the case for most people as it's not a well publicised syndrome. I would find it odd that so many people could come up with unusual symptoms such as the irresistible urge to move which only affects you in the evening or at night as a result of a mental condition but then were are all wired i similar ways and have the same brain chemistry (e.g. dreams of falling are common) so it's not impossible. I have found dopamine agonists work very well on the rare occasions I need to take them but nothing else has come close apart from COVID injections which again I find very hard to attribute to a placebo effect. I'd agree the wide range of symptoms and the variety of therapies which have mixed success does make it feel like there's no single cause but I suspect that's because we are very complex organisms and dopamine has many different uses in the body which are not well understood or easy to fully understand.

I hope the therapy works for you and that you keep us updated because it may also work for other people. That's the great thing about this forum - we share what works.

[WideBody]

Our story begins in the 17th century, long before Netflix made insomnia trendy. A young Dr. Thomas Willis stumbled upon patients plagued by an unsettling phenomenon. They described an irresistible urge to move their legs, especially at night, accompanied by a creepy crawly feeling that just wouldn't quit. Now, Willis wasn't the kind of physician to brush things off as "just restless legs." He was a Sherlock Holmes of sorts, determined to crack the medical mysteries that plagued his patients.

Fast forward to the 19th century, and enter Dr. Willis Ekbom, a Swedish neurologist with a knack for picking up where Willis left off. He noticed a curious pattern – many RLS sufferers also had low iron levels. Now, this wasn't just some random observation; it was a clue.

Ekbom, like a true detective, delved into the depths of medical literature, searching for a connection between iron and the nervous system. He eventually discovered that low iron disrupts dopamine production, a key player in the brain's movement control system. Eureka! A piece of the puzzle finally clicked into place.

But the story doesn't end there. In the 1960s, scientists made another groundbreaking discovery: RLS patients had significantly lower dopamine levels than the average person. This solidified the link between the brain, dopamine, and those restless legs.

Armed with this knowledge, doctors turned to a logical solution – dopamine-boosting drugs. And guess what? Initially, it seemed like a miracle cure! The restless legs calmed down, the urge to move faded into oblivion. It was like waving a magic wand over the RLS monster.

But hold on, history buffs, there's always a twist. As time went on, a dark side to the dopamine drugs emerged. Like a genie granting wishes with a hefty price tag, long-term use led to nasty side effects, including addiction and a phenomenon called "augmentation," where the RLS symptoms actually became worse.

This unexpected turn of events forced the medical world to reconsider their approach. While dopamine still plays a role in managing RLS, it's no longer the first line of treatment. Today, a spectrum of options are available, including lifestyle changes, iron supplements, and other medications with fewer side effects.

It's like low dopamine is the symptom and low iron is the cause. Wouldn't it be better to treat the cause not the symptoms?

[707twitcher in reply to WideBody]

Great history and summary - thanks. I was wondering myself about the role of dopamine. If that were the problem, wouldn’t THC help with RLS? (BTW, CBD is said to be a possible dopamine receptor repairer) But I think the experience of RLS sufferers is that it only drugs you back to sleep(assuming Indica not Sativa); it doesn’t stop RLS symptoms, right? I don’t know if different DAs affect different dopamine production activities - motor vs. pleasure?

Also wondering if low dopamine in TLS sufferers means we’re a sadder, more easily depressed group (and do DAs change that when we’re on them)? Is this a partial explanation for why withdrawal from DAs is so hard?

This is quite fascinating….