Sodium channel blockers

General
21

Hi Elizabeth,

Listen - i had the same struggle. I was close to suicide this year with it all.My life has been taken from me. Im bedridden and disabled by EM. I have LOTS of research validating lidocaine/mexil treatment. Lidocaine is used either as a one off test to see if you respond to sodium channel blocker or as a treatment depending on your response. Mexil is used with or without lidocaine . Bennett does not have to be involved. You need pain management clinic/specialist. Mexil is helping me - its a miracle! Lamotigine does not help- it causes more painful side effects and calf cramping - i tried it. It is not an analog of lidocaine so thats why no effect. Elizabeth either message me your number privately or phone me- ill send u my number. I know what you are going through - so does laura... we all do. I know you are getting worn down not only physically but emotionally but stay strong. Relief - to some degree is available but you have to fight for it. I never thought i would get any release or respite from this but after taking mexil for 2 months i now have fleeting moments of respite and I am starting to walk very tentatively and only few steps a day with sticks.That is such a miracle.I still cant believe that mexil is helping me like this.

. To reiterate - i have EM everywhere. It started in right knee - went to feet- other knee- legs- both hands, arms- scalp- ears- eyes and internally( like a cystitis thing).I am in constant flare mode - with and without the lobster redness. Ive had 2 operations on swollen eyes before they realised it was EM too. Take photos daily, keep diary, go to GP every week, monitor your BP , pulse tends to be low and contact PALS. Listen, if you have EM or any refractory pain its unethical in UK to with hold treatment. Drs , specialists dont know or understand the disease like we do.You need to educate them.

You say its pointless re: pain clinic. No- its not. You have to keep on at them, on at your GP for them to take you seriously. Another route I took was - accident/emergency. Go and be admitted - just do it- tell them about the pain - you cant stand it anymore - they will run tests/observations, which , as we know, will be negative BUT they will advise immediate referral to pain clinic on discharge sheet. That sheet and the A/E route gives you more kudos to 'how ill you are'. Shouldnt be so but it is. As i said. phone me. We can talk.

God bless

mads x

22

I've read several articles on using first lidocaine drip, and then mexiletine orally, with success, so the information is not being kept from us. And as for "why is just inherited EM being studied", 1) It's not. Most researchers are studying all forms. And 2) Inherited EM is an easier problem to uncover. (Also the myeloproliferative problem, which is usually a clotting problem.) The inherited form is a mutation of a specific Sodium Channel protein, on a very specific gene in the DNA. Genetics and gene manipulation is still very new. Probably solving the Down Syndrome problem (also a gene mutation) would be just as easy as solving the EM problem. As for how to determine if yours is inherited, they know which gene it is and where, so I imagine a genetics test specifically for that gene can tell. Google it.

Just reading this site alone is enough to know that the same treatment does not work for everyone. If it did, problem solved! It took from the beginning of germs until the last century to get antibiotics, and to discover insulin, and medicine is advancing so much faster today. We probably should be more appreciative of the efforts of those who are doing the research on EM, like the Mayo, Rochester, and the Univ. of Oslo in Norway, and Yale Univ., and a university in Scotland, to name a few.

I hope the best for all of us, and those researchers!

23

Hi elizxabeth,

lamotrigine caused severe cramping in legs and muscle weakness in me. I took it tritated up to 200 mg for 6 weeks to give it a good try. it didnt help my EM at all- but thats me. As Jane so rightly says we all respond differently and the lidocaine/mexil treatment has been validated in several articles so they shouldnt be with holding treatment from you. In UK ive been through this stuggle and i repeat it is unethical and you can complain to PALS who will act immediately on your behalf.. Mexil is not poorly tolerated to my knowledge. I have been taking for 2 months -side effects are unpleasant but managable and nothing in comparison to my EM. Again - depends on person. You are monitored and reviewed monthly in Uk.

Actually i dont quite understand why they havent done the 30 min- 1 hr lidocaine test on you - thats how they see if you are a sodium channel blocker candidate.

God bless

mads

24

I read on the TEA site, research section, a letter from Dr. Waxman (Yale U.) on why research on Inherited EM benefits all EM patients. He says there has been some research showing the Nav1.7 sodium channel protein (the one that is mutated in inherited EM) has also been shown to be involved in pain for burn patients, as well as some neurological-problem pain, with no mutations of Nav1.7. (He gives links to these sites). He said this means that some types of EM, non-inherited, could also be responsive pain-wise to treatments that work for inherited EM patients.

There are several articles online about Lidocaine drip, followed by Mexiletine orally, being effective for kids with the inherited form. Lidocaine (and Mexiletine) are sodium channel blockers (with a pretty strong effect on heart muscle, which is what they're usually used for). So there IS a developing research connection to EM there. Maybe showing some of that to your doctors could get their attention? Some of the sites are PubMed, which only gives the abstract and then you have to pay for the full article. But just about any doctor has access to PubMed, so just show the abstract - it gives the general idea, anyway. www.ncbi.nlm.nih.gov/pubmed/15741349

Good luck.

I took in a few print-outs on EM research to my Dr. (who is very open to reading them). One listed a number of meds to try. She immediately focused in on Lidocaine Gel (probably because as a gel, it has less side effects). I first soak my feet in plastic bags in cold water till thee redness and heat get out - then, using a plastic glove, apply a very thin coat of the gel (it's $63 a tube, but that should last awhile) to the top and bottom of my feet. It feels wonderful almost right away, and then I get right in bed. It lets me get some sleep, sometimes all thru the night. The Dr. said, though, that I have to NOT use it for at least 12 hours straight of each 24 hour period, to keep the effect from diminishing. I choose the daytime to take that 12 hour break, when I can soak often and elevate.

25

Ooooh! Sorry to bombard you all, but I just found a potentially useful site - an article called "Recent developments regarding voltage-gated Sodium Channel Blockers for the treatment of Inherited AND Acquired Neuropathic pain" - that's all of us (I haven't read the article yet, its's a long one - but I'm fixing to). It's at:

www.ncbi.nlm.nih.gov/pmc/articles/PMC3185237/

Maybe doctors will sit up and pay attention. This is the National Institutes of Health site.

26

They are working on it - the question right now is just how long will it take before something is available and then comes the next question - how expensive will it be and how will Insurance Companies react. Let's not forget *Big Pharma* wants to make money and Insurance Companies don't want to spend any. I wish all of us Good Luck.

27

I agree that the Pharmaceutical companies are totally out for the bucks! Without adequate government regulations (of pharmaceutical Co.s and Insurance Co.s), what can we do? Vote! At least we live in a time when Science is advancing fast and there's a chance for helpful discoveries. The fact that it's money-driven is both nuts and a strong incentive for research. Sigh!

It's the research at Universities that is bottom-line, because what they discover is what tells pharmaceutical co.s how to develop meds.

28

Hi elizabeth ,

As far as I see it you are highly informed and have been pretty much diagnosed . I dont quite understand why you have not been given the 30 min lidocaine test. That would validated whether you are sod channel positive.It could be you are stressing over a possible treatment which may not benefit in any way . My research qualifies extant evidence that sodium channel blocker must be the analog amino of lidocaine to work- As you know mexil is that - but to reiterate it has to be passed by FDA as unlicensed in UK for use.You must be monitored so buying meds off the net is dangerous

We are very similar. I found that the antidepressant route caused serotonin rebound syndrome- all norepinephrine etc... only exacerbated symptoms.

Re: antihistamines- i experience same except with LORADATINE at 40 mg day. These older style histamines function differently. I also have a 3 step programme incorporating 2 other histamine drugs. I find these do not create side effects and do help some what with vasodilation and constriction.

Lamotrigine - no use. I tried.

Are you on Gabapentin or pregabalin? What are you actually taking at present?

Re: EM research - i have plenty of empirical case studies, cochrane reports, cohort, longitudinal studies etc.. if you would like.They are all equally as valid.

My offer to talk on phone still stands.

Personally, I would contact PALS , present your case immediately and let them handle it.This is clearly unethical

Alternatively, you could contact my specialist and see him privately if not on NHS. He is very pro active. I have some of his research if you interested. He is truly helping me. Im on the lido/mexil combo for 2 months now and things starting to change - fleeting moments of coolness, etc...I even managed to walk through to my kitchen on sticks.I believe that this is the way forward for many of us.Ive spoken to fellow sufferers on this combo who are experiencing significant respite and remission.Any relief is a miracle.

Thinking of you

God bless

mads

PS: re: bloated toad. the lidocaine and/or mexil does work on autonomic. Im becoming more 'human' daily x.

29

Elizabeth, Thanks, I hadn't thought of the anecdotal problem. I took each case as yet another addition to the sum knowledge, but I see now that the Doctors don't think that way.

Are you saying that you can mail-order prescription drugs from the US without a prescription? That's wild! And here in the US, we look to Canada or Mexico for that!

I've Googled what you said about Nav1.7 overactivating sensory nerves paralleled by inactivation of sympathetic fibres. And the vascular symptoms. I have it on another tab waiting till I finish this. Thanks for the info - I'm seeking all I can get.

Also thanks for mentioning that lidocaine causes a rebound effect for you. I only use the gel before sleeping, and if I am having the same, it was the next morning and I didn't think to connect the dots. I'll watch for that.

And mostly, I'm so sorry for the facial involvement you are experiencing. That sounds like an even worse nightmare. I hope you can find relief.

Jane

30

Wow, thanks, Elizabeth! Those last two paragraphs respond directly to some questions I've had! I'm printing out that article now.

I've read in several places that viral infection is a possible onset cause of EM. Maybe your original suspicion is also part of it? You probably already have heard of some virus suspected as the cause of an EM "outbreak" in China around 1987 or so. I don't think it was proven, but the virus was present. And IF virally induced, it might not matter exactly what virus - just how your nervous system was affected.

It's wonderful that your well-read about all this. For yourself and all of us. Thanks!

Jane

31

Elizabeth, I'm so sorry. I want to have something to say that will relieve you, but I know there is nothing.

I'm thinkiing of you. I know that sounds lame. But I am

Love Jane

32

Hi Elizabeth,

DO NOT give up on the infusion and follow up, from what I have read this appears s to be a very effective treatment. I am from the UK , now living in Australia and my Daughter has EM. I have had to be very forceful on the lidocaine Infusion treatment for Her. Same in Australia , risky procedure, not on the PBS list. Having sat with my Daughter through nine months of torture I cant begin to know the pain you are going through but I have a very god idea. Best advice I can give is push, complain, shout Kick and scream, get your local MP to take up the case- the squeaky wheel gets the most oil. I do not normally subscribe to that point of view for anything else but the pain of seeing a loved one suffering has pushed me to have this stance. so far it appears to have worked , they are lining things up to make this happens we speak.



elizabeth said:

Husband saw duty GP last night, in floods of tears. She agreed I should be admitted to hospital for pain management. Saw usual GP this morning, sympathetic but says it's unlikely that she will be able to persuade anyone to follow the lidocaine/mexiletine regime outlined in the letter from the specialist at NHNN because it's an off label treatment, no on is legally bound to prescribe a treatment or medication unless it's writ in stone as being proven beneficial for a particular condition (and for mexiletine, that condition is solely cardiac arrhythmias). The only hope of getting a lidocaine infusion etc is if someone is prepared to put their neck on the line and take a brave decision on my behalf, which (having had long discussions with a GP friend of mine about all of this) is actually highly unlikely in the current climate within the NHS.

I warned her that I'd keep munching through my trunk of medications until I find a permanent way of shutting out the pain, she understands that and has prescribed more diazpam so I can maintain my semi-coma, but any beneficial effects of this will wear off fairly soon. She said it was unlikely the private hospital would let us self fund treatment without private insurance, due to the potential risks involved should something go wrong during the infusion, which is what happened when we tried to arrange one a couple of years back (the hospital just cancelled it at the last moment when they found out).

Treatment with lidocaine/mexiletine for EM is not at all straightforward in the UK, it's solely reliant on finding a doctor prepared to take a risk and put their career on the line on your behalf.

33

Hi, Elizabeth - I am no Dr. (for your sake I wish I was), but I read of EDS on wikipedia and it is apparently a mutation of a collagen protein, not a sodium channel mutation. Your EM and EDS don't sound like they're genetically linked (though you could have mutations for each). But for sure the EM could be part of the "symptom" syndrome. Maybe the EM pain would be lidocaine-sensitive, even if the EDS isn't? Since only nerve and muscle (including heart) cells fire electrical impulses, they're the only cells that have voltage-gated sodium channels in them. Lidocaine blocks the sodium channels in nerve and muscle cells, preventing or slowing their firing of impulse signals. Pain signals can't get through or are diminished, which is why lidocaine works for the dentist and is used to slow heart rate. EDS would be lidocaine-insensitive because EDS doesn't occur in nerve or muscle tissue. And EM doesn't occurs in connective tissue, that I know of.

This would be an expensive solution, but could you possibly afford to come to the US and pay out-of-pocket (sorry) to get the initial Lidocaine IV drip (isn't it typically for a few days?) and then the transfer to oral Mexilitine, which maybe you could refill by mail from the US or Canada? You'd have to be sure the Dr. you scheduled with was one who would do this. But that info is probably on the internet. I know, though, that if the IV drip has to be done in hospital, it could cost a LOT. Unless a Dr. would do it in his office in the morning and watch you for several hours after (make sure your heart wasn't complaining), then send you to a hotel (or some EM patient's house???) for each night. (that won't work, though, if the drip is 24/7 over several days). I know all this is a wild thought, but...??? I sure couldn't afford it myself. Also, I don't know how safe Mexilitine is and if a Dr. would feel ok with you living across the ocean and unable to get check-ups.

I wonder if they would do similar treatment in Norway, Univ. of Oslo? They do EM research there. Or the Netherlands. I saw an article here on a guy who had a hip replacement - he went to the Netherlands because there were no "hidden fees" there and it was $10,000 instead of $100,000 like here. Staggering, either way! But a lidocaine drip would be less.

Maybe all this is dreaming, or maybe not. I just felt I had to suggest it. I worked years in Hospice nursing, which can involve strong pain occassionally (NOT always). So I'm still conditioned to try to solve stuff even when I can't.

OH! In case you could go out of country for Lidocaine/mexilitine treatment, maybe you should ask if folks withOUT genetic EM get relief from it (in case sodium channels are not always the problem in non-inherited EM?) And, get a genetic test for EM? If positive, you'd be pretty sure lidocaine could work, though I suspect it would work anyway.

Thanks for letting me go on. I'm hoping and asking for your path to relief to open before you.

Jane

34

Elizabeth, thanks for updating me. Your condition sounds awful! I hope you find help soon. If I hear anything, I'll say.

Jane

35

I'm so sorry for you! I only have it with my feet. It looks so painful. Maya you find relief!

Love Jane

36

All a bit confusing, from what I can gather it has a been very effective in cases in pediatric genetic EM. Very much a case of what works for some doesn't work for others and therein lies the rub with this dreadful disease. I will share my daughters experience with this treatment, everything crossed at the moment.

37

I'd like to keep linked in to this as I think you are on to something with lidocaine/mexiletine. Well done for approaching FDA commission. Im up for joining forces with you!

best

ajh

38

You nailed it, Elizabeth! Different versions, different neural pathways, different origins. The more I read and learn, the more that sinks in. And the farther I feel from zeroing-in!

Jane

39

Hi Guys-

RE: Sodium channel blockers .

If anyone has any questions or needs any research to help fight their corner with specialists just message me.

If you have any EM related research- articles- information - please share it - simply post as an attachment or link.

We need to educate ourselves in order to educate our specialists

Together we can work towards making symptoms more manageable

Comfortable night to all

God bless

mads

40

Great to see people finally getting appropriate treatment. Good luck to all. Please keep posting your results

ajh