New research into Neuropathic pain:
 

This was posted on General forum this morning, but it
has potential for PNers IMO....

http://news.ucdavis.edu/search/news_...lasso?id=11258

I'd like to know which "lipids" this article refers to.

It looks like they're concentrating on diabetic neuropathy, which I guess is much more common than for people who aren't diabetics--like me!

Why of course they're naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid. :rolleyes:

http://www.jlr.org/content/51/12/3481.short


:D
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Are they basically talking about fish oil, MrsD? I'm trying to peel back the scientific jargon, and that's where I seem to have landed.

I never knew what EPA and DHA stood for!

Still trying to understand what they're saying, but it's difficult because when I read the scientific research reports I only understand about every fourth word.

If I try to get this is in plain English, this is what I'm gathering...

- ER Stress plays a significant role in neuropathic pain.

- ER Stress is mitigated by EPA and DHA which have an analgesic effect in the body.

- EPA and DHA are broken down by soluble epoxide hydrolas (sEH) into diols taking away their analgesic effects.

- The idea is to block sEH from breaking down EPA and DHA so they can in turn block ER Stress.


This is the UC Davis patent for "Treating Neuropathic Pain with sEH Inhibitors." Let the games begin.

http://www.google.com/patents/US20150065540



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It also seems to me that providing MORE fish oil would eventually override or use up the enzyme, so perhaps until there is an inhibitor of the break down enzyme, maybe just a bit higher dose would help?

That's what I was wondering. It would be an expensive experiment, but I might try it.

Interesting to my situation, I've seen estrogen referred to as an "sEH suppressor" in one report (can't drum it up at the moment), but this report seems to indicate the same:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972065/

Estrogen, soluble epoxide hydrolase & cardiovascular injury

"17β-estradiol may regulate an emerging novel therapeutic target against CVD – soluble epoxide hydrolase (sEH) . Arachidonic acid is converted to endogenous lipid epoxides epoxy-eicosatrienoic acids (EETs), which sEH (the cytochrome P450 [CYP] eicosanoids-metabolizing enzyme) degrades to 1,2-diols (dihydroxy-eicosatrienoic acids [DHETs]). High sEH levels decrease EETs and increase DHETs, whereas inhibitors of sEH increase the EETs to DHETs ratio in animal models."


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I didn't understand a word of this. :o

New molecular mechanism of neuropathic pain in mice

http://www.neuroscientistnews.com/re...thic-pain-mice


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That looks very promising.

Notice that in the neuropathic diagram, it shows that increased glutamate = pain.

This is why avoiding MSG is important.(monosodium glutamate)

Nice pictures too!;)

Excitotoxins
 

RE: Excitotoxins

Blocking NMDA receptors with Namenda

Namenda (memantine) is a medication with FDA approval for use in people with Alzheimers. This med acts upon the glutamatergic system by blocking NMDA receptors.

This med is also sometimes used in pain management, for chronic neuropathic pain.

This medication (like so many) has many potentially serious adverse effects, including but not limited to heart issues, nervous system issues (including potential for Tardive Dyskinesia) and many other potential complications. Please ask your pharmacist for potential adverse reactions/side-effect info.

I'd had this med prescribed for me in an attempt to quiet neuropathic pain several years ago. After a 90 day trial, I did not find this med helpful enough, in my case, to further chance the potential complications. The prescribing physician had felt I was overly concerned about the potential adverse reactions. I had kindly/gently, yet strongly, disagreed with him. I was experiencing no noticeable assistance with pain from adding this med for 90 days. Just my own experience with this med. Someone else may experience remarkable results.

Here's an article about NMDA receptor agonists' failures and successes:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC534915/

Lessening Exposures to Excitotoxins

It's safer, in my opinion, to lessen exposure to excitotoxins as much as possible.
(I know MrsD also mentions this often.)

See this article for more information:

http://americannutritionassociation....ns-taste-kills

Hope this info. helps somehow.

To Our Healing! :grouphug:

DejaVu

Deja.... do you know about the magnesium lotion? Magnesium also blocks the NMDA receptors in the periphery.

Morton Epsom lotion:
Many of us here use it with great success. It also relaxes muscles and improves circulation.

This is inexpensive and works wonderfully, it even lowers my hypertension to almost normal. I only need a small dose of betablocker now instead of 3 drugs.

Walmart and Walgreen's have it on the shelf...and it is at Amazon online... but not all stores have it yet.
Use about a quarter's diameter once a day...at night if possible.
Divide that up 1/2 for each leg. I find it lasts more than a day for me, so you can rotate locations. A fingertip dollop works for the neck.

http://www.walmart.com/ip/Morton-Uns...fl-oz/23711655

Hi MrsD,

Thanks for mentioning this to me! :)
I had found this lotion just 2 months ago, by chance, at Walmart.
I use it nightly.
Thanks for the dosage info. I will use it more frequently, and in more areas!

It's good to be back here on the PN forum, and at neurotalk in general!
I am feeling much more hopeful than I was even three days ago.
When I get away from this group for too long, even due to increased illness, I start to feel the options are too limited and the conditions too progressed and it feels hopeless. More options become available and I have had difficulty staying updated on my own.
It's so helpful to be reminded there are options and there is hope!

Many thanks to you and to all members here for sharing so openly and for offering mutual support! :grouphug:

To Our Healing!
DejaVu

NIH has granted $4 million to the company UC Davis founded to pursue this SEH inhibitor approach to treating neuropathic pain. :)

http://www.centralvalleybusinesstime.../001/?ID=29766

"Now known as EC5026, the compound is “a potent, orally active and a non-narcotic analgesic that does not adversely affect the brain, gastrointestinal tract, or cardiovascular system,” says Alan Buckpitt, the company's vice president of pharmacology and emeritus professor of molecular biosciences at the UC Davis School of Veterinary Medicine. “The compound effectively treats pain in preclinical models at low oral doses with no apparent adverse or addictive effects. Preclinical studies demonstrate efficacy that exceeds current therapies for diabetic neuropathy.”"

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If it all works out I wonder how long it will take to get to market?

Cliffman :)

The mention of "early" clinical trials suggests that the process is just beginning. That means 5+years or more.

Namenda 28 mg at night
Memantine 10 mg 1-3 times per day

Amazing!

Ran out of nucynta
 

What can I do to control
PN pain

Edmund UK
 

I also have serious pain in my feet. I have been through all the tests and have had Steriod injections in my toes, Nortons Neurona. No effect, only more pain.
My life has been a complete misery for the last 18 months and I don't think that doctors are very much concerned about the condition. Although I am in my 80s I have been very active, outside every day in all weathers until affected by this. Treatment, Lyrica,two a day and the cream with the very hot chilli. The tablets help but I don't think the cream is helping. I follow these very helpful pages and some of my information I have taken note of and will present it to my consultant. AI hope Susan that you will get some helpful advice as I hope the same! In anticipation, thanks.

EdmundUK
 

My previous post said that I was hoping to present some useful info obtain fron this very useful Forum! After a long wait for the appointment with the consultant at my NH hospital, the biggest waste of my time ever experienced! Full of hope for some sort of info from him to ease my very severe pain in my feet, I struggled to his department only to have less than 4 minutes of his time. After he had been told by his assistant in another room he came in to see me, hand outstretched with the words" I was right then about your condition " He couldn't be anything other than Right the idiot. I had already been sent by him to check for Nortons Neuroma, had the Steriod lnjections. He knew about the results so one doesn't need to be a brain surgeon to sort that one out. I came out of that hospital more that greatly dejected and no further forward in getting any relief. I tried to tell him about a little info from this Forum, B12 , Epsom salts etc, he just did not want to know. Mention the Internet to doctors and they are just not intrested. Sorry to go on so long. Edmund.

PN
 

My PN is now getting quite severe , my Doctor has raised my Lyrica to 100 twice a day. I am also using the hottest chilli cream, forgot the proper name! Had all the tests, I must say that the specialist l saw for a couple of minutes , I felt disgusted, was of no help at all! I wish all PN suffers well.

I have to wonder if your hot pepper cream (capsaiscin) is making things worse? Many of us here cannot tolerate this product, including me.

I use lidocaine on my feet during a flare. In the US there is a new lotion called Aspercreme lidocaine 4%. But I don't see it in the UK.

If you can ask your doctor for either Lidoderm patches RX, or a cream with 4 or 5% lidocaine made up for you, you could try it.
Apply to the tops of the feet...and up to and including the ankle.
This is a very numbing product and would work better for you I think.

If you get the Lidoderm (lidocaine) patches, 1/2 on each foot is enough. You might have to tape them down too...as the adhesive is not very strong with them. But the pain relief is nice. It takes about an hour to get going, so be patient.

There's a possibility this might change in the future: Modified chilli ingredient may be a new way to relieve severe pain | Spectator Health

Capsazepine is supposed to have all the advantages of capsaicin, but none of the ill effects. Will be interesting to follow this.

Thanks, Wide-O--- that looks promising. Lidocaine works by blocking sodium channels and prevents sensory information from being transmitted to the brain.

I found out yesterday, that Aspercreme also has an OTC new version of RX Lidocaine patches... 4% instead of RX 5%.

The lidocaine really works well for me in the lotion/cream version though.

I really don't think you can get 4% in UK however except on RX.

I read that the WalMarts here have this, much less expensive than Amazon so far.

And me! I hope they find something soon to help us poor sufferers!

I will ask my Doc for some. My feet are killing me!

I would like to see more information on straight forward PN. The pain I suffer is quite serious and drives me to distraction! I am very old so I just put up with it and hope that there will be help and a cure for you all in the future.