Is any research being done anymore on non-inherited EM?

General
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I can't find any research done in the last 5 or more years that is on NON-inherited EM. Only approximately 30% of EM patients have the inherited form. Yet once a genetic mutation for EM was found, it seems all non-inherited EM research dried up. For awhile there was a lot of investigation into things like "what's really going on inside those feet, blood vessels, nerves, etc.?" Now it's only about the SCN9A gene. That's wonderful, but what about the other 70% of cases?

Anyone seen anything new out there?

Thanks, Jane

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Thanks Tizzy,

Your comment makes complete sense. I hadn't looked at it that way.

If a gene mutation of sodium channels is the key to all neuropathic pain, then the work being done will be an incredible blessing. I wonder, though, if there are other things, problems that could create a hyperexcitable neuron. Or, if all ways to hyper stimulate the neurons involve sodium channel activity, it doesn't matter - the meds invented should work.

If the EM was caused by a period of exposure to toxins, that are now no longer around, then the damage is maybe not "ongoing" hyperexcitability, but a permanent degeneration for another reason. Hmmm. In that case, it sounds irreversible.

Sorry, I'm kind of "thinking out loud" here. I have heard of the arteriovascular shunting theory. It is actually not new. The Norwegians (Oslo University) were looking into that at least in the late 1990's. I think it makes total sense, but still leaves the cause for the shunting in the first place unknown. I suspect it could start with an autonomic small fiber nerve degeneration (small fiber neuropathy), for whatever reason. This might diminish signals to the nerves to the constricting smooth muscle around arteries, so that the muscles fail to tighten and the arteries remain dilated. Over time, with blood pooling, the capillaries and vessels and natural shunts stretch, and finally the feet get red, hot, swollen with too much pooled blood. Anyway, that's the best theory I have for my own case, since I know I have small fiber neuropathy due to degenerating sensory and autonomic nerves in my legs (I had skin biopsies).

For me, I do put my feet in about 60 degree water, with gallon ziploc bags on each foot to keep from getting my feet waterlogged and have the skin break down. If my nerves won't constrict my vessels, the cool sure does. That and elevating them.

Who did you send the email to, about your concerns?

Thanks for writing, and I hope the best for you.

Jane

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This has been on my mind too. Even if something can be done about the neuropathic pain such as the red burning that still leaves a lot of pain from the purple swelling. If you can't stop the swelling you will still have the pain. I can't go more than a few minutes sitting without my legs up before my feet turn purple swell and hurt even when not too warm. Every time I go to a doctors appointment I have to ask for a chair to put my feet up. The rest of the time I live in a recliner to reduce these episodes.

Does anyone else get the swelling , purple painful feet without necessarily burning?

Take care,

Alina

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Hi All, my feet get the purple and pain without the swelling I also have extensive small fiber neuropathic (SFN) pain, everyday and almost all day. EM (i.e., the burning) mostly comes in flares. I still haven't found my limit of activities to prevent them. The meds I am on are Lyrica and Tegretol and they take edge off much of the SFN except at night. I cannot take things like Tramadol because I cannot sleep taking them.

I participated in the Xenon saliva test but have not heard back yet. I was exposed to dry cleaning chemicals in drinking water for about five years (20 years ago) but no one wants to take that seriously. Most of the neurologists I have seen will not even discuss EM (especially not the government ones). I have searched for studies but none yet.

Blessings,

Don

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Hi Jane,

I don't know about any research. I've wondered if the drug Xenon are developing for the genetic variety would also help everyone else?

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I agree with you Tizzy re: gene mutation (and to be discovered and discovered variants ) of sodium channels

Yes, Re research on non inherited EM, but its still in infancy- application.

Tizzy. I can put you in contact with someone to discuss this matter.

Xenon study is on EM. The genetic aspect pulls in the funding ;) Drug will be for all EM and other refractory pain. New drug is a sodium channel blocker without the cardiotoxicity of Lido/mexil combo. They have another EM study in pipeline .

mads

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Mads, thanks for the information! Great things to hope for.

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Thanks Veerla for that information. We did post about the 'Safety and Tolerability of Lacosamide in Patients With Gain-of-function Nav1.7 Mutations Related Small Fiber Neuropathy' , earlier in year when they were recruiting.

Based on other neuropathic studies Lacosamide should be more effective than carbamazepine and lidocaine at selectively blocking the electrical activity of neurons that are chronically depolarized compared with those at more normal resting potentials. In other words its a novel sodium channel blocker but with less toxicity. Valporate is another... there are several. Its finding what helps you better manage symptoms. It is available in UK too .

Any research you have is so welcomed. You are most kind offering to share with the community - bless you. Hope you are feeling little stronger x.

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Tizzy, the genetic mutation form is quite painful from what I've read. It causes hyperactive sodium channels along the nerves, that cause the electric impulse, to be faster than normal along the nerves specific to pain. And they also have the heat and redness. I am guessing the genetic form's hyperactive impulses causes the pain and autonomic nerves to wear out and disintegrate, which is small fiber neuropathy. The Xenon research was specifically for the genetic mutation form, and dealt only with sodium channel problems.

Dazsa, absolutely the dry cleaning fluids would be able to cause nerve damaqe, which is what small fiber neuropathy is. That's a toxin, so it fits perfectly with one of the causes always mentioned for EM!

The Zenon drug is designed to help anyone with EM caused by a sodium channel problem, and I'm guessing genetic mutations are not the only thing that can cause that. Sodium channels are crucial to autonomic and nociceptive (pain-sensing) nerve impulses. Probably lots of things could negatively affect the Sodium channels in the nerves. When the drug is on the market, we could all try it and see. Then we'd learn who it helped and who it didn't. And if it did help, that person could figure they did have a sodium channel problem, from whatever cause (and get tested to see if it was genetic).

Alina, When I go to the Dr., or any place I have to wait, I actually take a small cooler with cold water, and ziploc bags for my feet. Or sometimes I carry crushed ice in a gallon ziploc bag, put on slightly thick socks, and lay the ice over or under my feet. Or both. It feels great, long as I have socks to keep from freezing them. I used this method on an airplane - took the bags with me, and after the check-in gate, went to a food counter and asked for ice.

I looked up lacosamide. It's the generic name for Vimpat. I'm going to find the post on its safety - thanks, Mads.

And thanks everyone, for responding!

Jane

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Sorry to come late to this discussion. I've been in hospital

As others have said, the reason the research is done on primary EM - as opposed to only inherited - (I'm in the Xenon study I have primary EM but don't have any family history of it) is because of how research into treatments is done now. Genetics can rule out the variables.

Another reason is because secondary EM is caused by another disease, so you couldn't be sure if the treatment had treated the EM or the disease causing it.

As other people have said, the treatment should work for all forms of EM, plus other things like SFN, as it should cut down the amount of pain signals that are sent, even if you don't have a problem with your sodium voltage channels. SCN9A EM is a great test subject for these drugs, on the theory that if it works for those people. it should work for any type of nerve pain, as those people with the SCN9A form just have a pain "switch" that is too sensitive.

I don't know about the burning without the pain aspect of the drug. I think the idea is that the nerve signals cause the bloodflow problems, but that will be something we'll only find out once people with secondary EM test the drug.

Like many diseases, it may seem unfair that one form of it gets all the funding but it is simply that that particular form is the one that is the best test for the whole bunch.

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Good to know this information :)

210-DiagnosingSFNviaskinbiopsy.pdf (45 KB)
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I have a similar problem, even if I DO have the genetic form of EM. However, we don't have the SCN9A mutation. There is a misunderstanding and a lot of the literature acts like if you get tested and don't have the SCN9A gene mutation, that it means you don't have genetic or inherited EM. That isn't true. Only SOME of the people with genetic erythromelalgia have that particular gene defect. And it is a small percent! Something like 17% of all genetic EM has the SCN9A defect. So we fall into that category of "we have inherited EM, but nobody is interested in research for us either".

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Genetic can be 'familial' or sporadic ' non familial'. I agree with you, saying 'inherited' brings considerable misunderstanding. I have so called' sporadic'.... sounds like you do too. Lets just call ourselves sporadic mutations ;)

I heard that several novel genetic sequences have been found amongst some participants in the Xenon saliva test study. What do these sequences mean? I find it hard coming to terms with something I just dont understand. If its not genetic familial nor secondary to another condition/medication- induced , why did 'sporadics' get EM in the first place? I truly believe we have some common factor? A vunerability due to?????? Keeps me researching!.

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Yes, I like that. We are "sporadic mutations"!!!!! :)

mads said:

Genetic can be 'familial' or sporadic ' non familial'. I agree with you, saying 'inherited' brings considerable misunderstanding. I have so called' sporadic'.... sounds like you do too. Lets just call ourselves sporadic mutations ;)

I heard that several novel genetic sequences have been found amongst some participants in the Xenon saliva test study. What do these sequences mean? I find it hard coming to terms with something I just dont understand. If its not genetic familial nor secondary to another condition/medication- induced , why did 'sporadics' get EM in the first place? I truly believe we have some common factor? A vunerability due to?????? Keeps me researching!.

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I am feeling very stupid Moongirl but glad to have been educated. I didn’t know that there is familial EM without the mutated SCN9A but perhaps it puts my own experience into perspective. My father died young but I remember him suffering in the heat. He would never have discussed his symptoms with his children so I know no more. My daughter shows signs of heat intolerance and painful feet too but without neurological pain - as yet. I don’t want it to be genetic…



Moongirl said:

I have a similar problem, even if I DO have the genetic form of EM. However, we don't have the SCN9A mutation. There is a misunderstanding and a lot of the literature acts like if you get tested and don't have the SCN9A gene mutation, that it means you don't have genetic or inherited EM. That isn't true. Only SOME of the people with genetic erythromelalgia have that particular gene defect. And it is a small percent! Something like 17% of all genetic EM has the SCN9A defect. So we fall into that category of "we have inherited EM, but nobody is interested in research for us either".

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Hi, sorry to have not responded in a while - especially since I started this discussion. I just came back and am trying to catch up. I don't want to seem pushy, but it seems to me there's a lot of misinformation mixed in with the real stuff. For start, "genetics" comes straight from both parents. 99.9% of genetic material is exactly inherited. The only way genetics could be "non-familial" is if you are the one the mutation occurred in for the very first time ever (so that no one else in your family had it). That's extremely rare, tho possible. And you would then be the one to pass on a whole new line of EM victims.

Veerla's referenced article is indeed not about the best known sodium channel mutation, Nav1.7 (gene SCN9A). It IS, though, still about another sodium channel also on peripheral nerves, Nav1,8 (I think that's gene SCN10A).

These two, and about 7 or 8 other genes, are ALL responsible for forming Nav sodium channels in the new fetus. Nav stands for: Na is the chemical symbol for the sodium atom, v stands for voltage gated channel.

Nerves do not have "pain switches" like little buttons. Nerves do a lot of different things. Pain nerves send electrical potential signals to the brain, where they are INTERPRETED as pain, say in the foot. The way these signals travel up the nerve fiber (axon, like its tail) from foot to spine, where the signal is transferred to another nerve) is because Sodium (Na) channels, little gates all along the length of the nerve fiber, open and close to let sodium atoms into the cell. Sodium, like many atoms, has one too many electrons, so it has a negative electrical charge. This allows the inside of the cell to build up a negative potential. The sodium channels all along the nerve open not all at once but in sequence down the line, so the electrical negative potential runs down the nerve. This IS the signal in a nerve. When it gets to the next nerve, the electrical potential is passed on, till it gets to the brain, where (even tho it feels that the pain is in the foot) the pain is actually noticed.

With a mutation of a gene for a sodium channel, the channels function improperly. Usually, according to research, the sodium channels along the nerve are opening too fast and staying open too long, so that the signals are "too much". That results in excess pain, if its a pain (sensory nociceptive) nerve. If its an autonomic nerve that tells the muscles around blood vessels in, say the foot to constrict or dialate, then that function is over-done instead.

And over time, research is thinking, excess firing of nerves due to too much sodium inflow, due to genetic mutations of sodium channels, deteriorates the nerves themselves. The nerve fibers can die back. This is small fiber neuropathy.

EM can be caused by mutation (and a sodium channel mutation means ALL sodium channels in your body that are designed by that specific gene are defective) or nerves can die back from toxin or disease or chemo or a lot of other reasons.\

Or a person can have non-genetic malfunctions, meaning though their genetic (blueprint) material is normal, their personal information gets misread as their bodies develop as infants. The meds that work on sodium channels to slow their actions (which I think is the Zenon drug) might not work on all EM, since the causes may be elsewhere. I can't say.

I know I've rattled on. Sorry if I'm out of line. It just seemed that there is a lot of confusion. I'm no expert. When I was diagnosed, I went to the bookstore and bought a college neurology book and first learned how the nervous system works. (Turns out voltage-gated channels, like sodium or potassium, are on the ground floor of the system). Then I went to the research. It becomes clearer that way.

I hope we all are relieved thanks to research, very very soon.

Love Jane

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Thanks for explaining things so brilliantly Jane.

Wow, that was so clear even I understood it. I can use this to explain EM to the pain clinic people. :)

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I would be the rarity, then, that a familial genetic form of erythromelaglia just started with me. I am the youngest of 10 children, and nobody anywhere in my family history has or had anything like EM. However, I have it as well as all four of my children. So I guess something went wrong somewhere with me.

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Wow, Moongirl! That IS amazing. No one before you has it but all 4 of your children. I'm really sorry.

I'm just a retired LPN (the bottom of the nurse-heap), so truly I am not "learned". But it really does seem you COULD be manifesting a new family link of mutation. That all 4 children, yet no one historically, in your family has it!!

Can your parents think of any toxic exposure when your mom was pregnant? Or do you, when you were pregnant? Or disease, maybe viral, or medications?

It's so rare, yet it's been happening for hundreds of thousands of years. I think that's how modern humans came about.

I just started reading a book on Epigenetics, which is where the DNA does not mutate, but the processes due to the DNA/genetic code, get mixed up and cause changes that are not genetic, yet can be passed on sometimes. I suppose your situation could be genetic mutation OR epigenetic alterations or misreadings. Or, some mystery way beyond my imagination.

I hope the best for you. You can get genetic, and maybe even epigenetic (if not now, someday) testing. But it still leaves you with the problem.

Thanks, Mick. I always fear I'm making no sense.

Love Jane

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You made perfect sense Jane and I am grateful for the clear thinkers who can explain things to fuddled headed people like I have become.