Epilepsy and Chronic Pain - Related?

[Endless]

Did you all see this article in the Epilepsy News page in the forum?

Twitchy Nerves (Literally) May Explain Epilepsy, Pain

The discovery about how nerve cells communicate focuses on the ability of neurons to release chemical signals to nearby cells through the axon, a part of the cell that functions much like an electrical wire by carrying an electrical signal to another cell.

Neurological conditions including epilepsy and chronic pain seem to be triggered by the stimulation of regions of cells in the brain that aren't directly connected to each other. By understanding how these regions are communicating, researchers may be able to come up with better treatments... Dr. Tasaki had measured these mechanical changes in all kinds of tissue — in the retina, in skin," Fields says. "He even showed that the whole spinal cord of a frog twitched when an axon fired."

The more I read, the more little puzzle pieces fall into place. I had muscle spasms in my back - bad ones. Incredibly painful. For years. They went away when I went on AEDs. My neuro said they weren't seizures and weren't related to the epilepsy in any way, and the reason that the spasms went away was that the meds just affect you in funny ways.

I've been searching for an explanation. Maybe it's the above, maybe not.

Does anybody else in here experience chronic pain? Has your neuro said that it might be related to your seizure disorder, or the root cause of your seizure disorder?

 

[daisy.girl]

this is very interesting.....
I have MS, severe migraines, chronic pain, 3 herinated discs, pain that radiates down my arm, and very achy painful legs as well as seizures.

 

[RobinN]

Inflammation of the nerves?

 

[Endless]

Atp

I'm very curious about why - the root causes - of epilepsy. New discoveries about why gives me hope that someday they may be a cure.

If you don't like heavy duty science, skip this. Seriously. The full article made my head hurt. Putting together these excerpts made my head hurt. The full article is heady reading for science gods (or godesses). Mere mortals like me have a rather difficult time with it.

BTW.... are there any Biochemists in here? I need some see-spot-run help, because understanding this stuff is crazy hard. (check out the full article on ATP)

The below talks about the role of sugar in the body in creating ATP which is the chemical that crosses between axons in the brain (axon = part of a neuron which is part of a nerve cell), creating cross-communication which can create the firing of nerve cells and twitching (which can lead to seizures or chronic pain).

Glucose is used by the body to make ATP. This made me have questions about the possible relationship between glucose levels in the body and seizures, which is a hot topic in the forum. Keep reading till you get to the punchline at the end.

...twitching axons were, indeed, releasing ATP... No synapse needed. Fields says this newly discovered system of cell communication does a better job explaining neurological conditions like chronic pain and epilepsy. Both involve nerve cells firing when they shouldn't, and studies show that this firing isn't triggered by signals coming across synapses, but it could be triggered by twitching axons releasing ATP...

Twitchy Nerves (Literally) May Explain Epilepsy, Pain


I wondered, "What the heck is ATP, what does it do, where does it come from, and why does it go haywire in those of us with a seizure disorder?"

Wikipedia has a big article on ATP. http://en.wikipedia.org/wiki/Adenosine_triphosphate#Glucose

ATP is the main energy source for the majority of cellular functions. This includes the synthesis of macromolecules, including DNA and RNA..., and proteins. ATP also plays a critical role in the transport of macromolecules across cell membranes... In humans, this signalling role is important in both the central and peripheral nervous system.

[A signaling molecule is a chemical involved in transmitting information between cells. Such molecules are released from the cell sending the signal, cross over the gap between cells, and interact with receptors in another cell, triggering a response in that cell.]

ATP is critically involved in maintaining cell structure... ATP is required for the shortening of...crossbridges required for muscle contraction. This latter process is one of the main energy requirements of animals and is essential for locomotion and respiration...

ATP is critical in signal transduction processes.... ATP...is transformed to the second messenger molecule cyclic AMP... which is particularly important in brain function, although it is involved in the regulation of a multitude of other cellular processes...

...ATP transfers energy between spatially-separate metabolic reactions.... ATP also plays a critical role in the transport of macromolecules across cell membranes.

The ATP concentration inside the cell is typically 1–10 mM... Typically, a human will use up their body weight of ATP over the course of the day... This means that each ATP molecule is recycled 1000 to 1500 times during a single day... ATP cannot be stored, hence its consumption closely follows its synthesis...

ATP can be produced by... using simple and complex sugars (carbohydrates) or lipids as an energy source. For ATP to be synthesized from complex fuels, they first need to be broken down into their basic components. Carbohydrates are hydrolysed into simple sugars, such as glucose and fructose. Fats (triglycerides) are metabolised to give fatty acids and glycerol.

The overall process of oxidizing glucose to carbon dioxide is known as cellular respiration and can produce about 30 molecules of ATP from a single molecule of glucose... Thus, at any given time, the total amount of ATP + ADP remains fairly constant.

Huh. After reading the above I wondered...

"Is there something haywire in the ATP production process in people with seizure disorders that results in too much ATP? (the article above says ATP remains constant, but didn't say anything about if that "constant" could be too much of it in some people.) Or is it that our axons leak ATP more readily than normal, and this creates the seizures? And if so, why (Robin mentioned below that nerve cell inflammation may be a possible cause)

It says glucose is used in making ATP. In some people with seizure disorders, could too much glucose in the system (Diabetes), too little glucose (hypoglycemia) or maybe too much fat affect the production of ATP?

Could too much ATP result in too much shared communication between cells in the nervous system, creating the twitching? Maybe not, because then wouldn't all our cells go haywire because they all use ATP? Or maybe our nervous system just more sensitive???"

Would love to hear an explanation or see some research on that. I Googled for awhile and didn't find anything on the relationship between glucose levels, the production of ATP, and the transport of ATP between cells. Or why our neurons may leak more ATP. Or maybe there was and I just couldn't understand the title of the article! :roflmao:

Paging all biochemist.... paging all biochemists....

 

[Nakamova]

I don't think too much ATP would cause seizures, in fact just the opposite: An increase in ATP in the brain catalyzes into adenosine, and allows adenosine to build up. Adenosine is basically the brain's built-in anti-convulsant -- it INHIBITS brain cell signaling. (Adenosine is also one of things that "tells us" we are sleepy. It builds up over the course of the day so when it gets high enough, our brains know it's time for bed).

ATP production is also triggered by the ketogenic diet and by Deep Brain Stimulation, both of which are used in epilepsy treatment.

Since ATP is created by the breakdown of glucose/sugar (glycolysis), then low blood sugar levels could lead to low ATP levels (which would mean low adenosine levels, which would mean less inhibition of abnormal firing). With diabetes, I don't think the problem is excess sugar per se, but the way diabetes blocks certain ATP channels in the cell, limiting it's transport, again limiting adenosine production.

Fun fact (from the wikipedia entry about adenosine):
Caffeine stimulation happens primarily because it inhibits adenosine by binding to the same receptors, and therefore effectively blocking adenosine receptors in the Central Nervous System. This reduction in adenosine activity leads to increased activity of the neurotransmitters dopamine and glutamate.... (This is why caffeine is a no-no for many people with epilepsy).

 

[epileric]

I wondered, "What the heck is ATP, what does it do, where does it come from, and why does it go haywire in those of us with a seizure disorder?"

ATP (adenosine tri-phosphate) is created as fuel for energy when we need energy and cellular activities in our body. I'm sure our levels of it increase during a seizure as fuel for our bodies because of how our neural firing, breathing, heart rate etc. all increase hence there is an increased need for it.

ATP consists of 3 phosphate groups attached to adenosine, a unit composed of adenine & the five-carbon sugar ribose. (c.Principals of Anatomy & Physiology by G.J. Tortora & B Derrickson)

When ATP is used, it is a phospate that is burned & converted to energy, turning the ATP (adenosine TRI phosphate) into ADP (adenosine BI phosphate).

Huh. After reading the above I wondered...

"Is there something haywire in the ATP production process in people with seizure disorders that results in too much ATP? (the article above says ATP remains constant, but didn't say anything about if that "constant" could be too much of it in some people.) Or is it that our axons leak ATP more readily than normal, and this creates the seizures? And if so, why (Robin mentioned below that nerve cell inflammation may be a possible cause)

My understanding of how it works (I hate to admit it but I can be wrong) is that even though the level is constant it is only produced when some is burnt & turned into ADP.

Could too much ATP result in too much shared communication between cells in the nervous system, creating the twitching? Maybe not, because then wouldn't all our cells go haywire because they all use ATP? Or maybe our nervous system just more sensitive???"

Again, because it's not produced until it's needed I don't think there could be too much.

I hope that helps. It was a good excuse to dig up my old text & look things up. I'll update you if I read any more on ATP (there really is a lot). I would suggest if you can find a copy of the book I mentioned before (Principles of Anatomy & Physiology) it explains things pretty well but borrow it, it's rather expensive.

 

[epileric]

Fun fact (from the wikipedia entry about adenosine):
Caffeine stimulation happens primarily because it inhibits adenosine by binding to the same receptors, and therefore effectively blocking adenosine receptors in the Central Nervous System. This reduction in adenosine activity leads to increased activity of the neurotransmitters dopamine and glutamate.... (This is why caffeine is a no-no for many people with epilepsy).

Cool fact. Thanks Naka

 

[Endless]

:adore:

Ah, HA! Nakamova is a scientist! (or plays one on TV). Thank you so much for the explanation!

I'm hoping you help me understand a few more things... they mentioned ATP as the agent that is communicating across axons, which results in the twitching. (ATP across the cell walls causes the twitching) ATP is a form of Adenosine. How come communication of ATP across axons would cause the twitching and therefor perhaps seizures or chronic pain (per the article), when Adenosine is an inhibitor? Why the opposite effect?

They also say that ATP levels remain constant in the body. It doesn't increase, it doesn't decrease. That would mean it doesn't matter how much glucose you have in your body. There must be some kind of self-balancing system for the ATP. I don't understand the explanation they gave for that. To use a metaphor: until they explain how putting more or less fuel in the car doesn't affect how much carbon monoxide is created, I'm not satisfied.

 

[Nakamova]

Hmm. I'll give it a shot (since the article didn't have nitty gritty details, don't quote me).

1. ATP is not quite the same as adenosine, rather it degrades into it. In a very simplistic way, you could say ATP = hypes cells up, adenosine calms them down.

2. ATP is an excitatory neurotransmitter (= bad for people with epilepsy), but ordinarily when it's released from the cell, it is co-released with GABA, which is an inhibitory neurotransmitter, so they balance each other out. I suspect that it's the balance with GABA that can get disrupted in epilepsy, allowing the ATP to "flip the switch" into excitation mode. Several things (like intercellular free calcium) can mess with with this balance by changing how certain synaptic receptors behave.

3. It sounds like the "twitchy" ATP is skipping the synapses, so it's taking a shortcut, and the inhibiting GABA lags behind. And it takes quite a few steps for the ATP to degrade into adenosine, and several more steps for the adenosine to then beneficially affect GABA. So the ATP is leapfrogging, while the adenosine and GABA are crawling. The inhibiting system can't necessarily catch up to the exciting system. (It's sort of like drinking 20 cups of coffee with one sleeping pill, and then wondering why the sleeping pill isn't making you sleepy).

(Digression: Lamictal is supposed to work by binding with proteins in the body, so I wonder if one of the proteins it binds with is ATP, thereby limiting ATP's excitatory role. Magnesium can also help keep ATP bound to proteins, which may be one reason why magnesium helps some folks too).

4. With epilepsy it's a short-term modification in the balance/uptake of inhibitors/exciters that goes wrong. Over time it can also turn into a more permanent change which is kinda what happens with kindling. And with chronic pain and/or peripheral neuropathy, it's a long-term change as well, a out-of-balance feedback loop involving the transmission of peripheral pain-inducing messages that unfortunately gets hardwired.

5. As for the levels of ATP, it's basically a closed system -- it's made from certain ingredients in the body, and then it breaks down into those same ingredients, and then it reconstitutes itself from those ingredients. It's always recycling itself. I think the key though is that this balance is maintained fairly constantly on a global level, but less so at a cellular level. So disturbances/extremes in sugar production may be affecting how ATP behaves at the cellular level, rather than at the global level.

And a final caveat -- I really only play a scientist on TV, so take all of the above with a large grain of salt (sugar?)

 

[Endless]

Very NICE Nakamova. :clap:

Fun with science. :rock:

 

[Endless]

I couldn't find anyplace else to post this, so I'll put it here.

Sheesh. It happened again. My mind raced in scribbly little circles (see posts below) and I couldn't stop it. Then I had a seizure. (a SP, jamais vu in this case.)

My doc says that since the mind scribbling around can last hours, it can't possibly be an aura or a seizure. Hmmm...

Now I'm so sleepy... I'm melting into the couch so I'm going to bed.

 

[Nakamova]

Some auras can last for hours, so why can't the mind-scribbling be an aura?

Although I do think its more likely to be due to the Lamictal, since it's a known side effect. Could it be that your mind is racing away while the Lamictal is at a therapeutic level, and then when the level starts to drop you have the seizure? If that's the case, maybe the extended release version of Lamictal would help. Or are you already on that?

 

[Endless]

I think the extended release lamictal is a good idea. I feel funny before for awhile before each of my doses. I'll ask my doc about it.

The mind scribbling isn't the lamictal. I've had it at least once on all the drugs I've been on.

My epi says auras don't last for hours. I've to to ask him about why - folks in here clearly experience what I do - auras that last from minutes to a day.

I told him about the buzzing/electrical feeling in my body & brain. He said it wasn't a seizure, and said it was anxiety. But when I went off trileptal so quickly I felt that buzzing feeling x 100. It was horrid. It peaked at day 2 along with about 5 seizures a day. Now I think that electrical feeling is medication related - the meds wearing off, or taking something else that's interfering with metabolizing the trileptal/lamictal. Not sure if I will discuss this with him, though. (What's the point?)

That's okay. I'm beginning to believe that with a little help from my friends, I'm just about as good as the doctor in managing my seizures and my meds. Absent the Pez dispenser doctor and Pez Lamictal (literally, see other post, search for it!)... How about we all take a little trip to Mexico together? We can swim and party and while we're there get big jars full of our meds CHEAP. No prescription required.

 

[Nakamova]

I'm with you Endless. I've learned from the web and CWE about consistently reported seizure symptoms and med side effects that don't seem to have made it into the neurology textbooks. For many neurologists, if it's not in the textbooks (or in the marketing handouts the drug salesman drops off), then they won't consider it, and they'll dismiss your concerns while disregarding your insights. I'm not saying that the docs are always wrong and that the patient is always right, but there could be more effort to listen and be open-minded. My doc doesn't even write down the side effects I mention -- you'd think that it might be useful for them to have their own patient database to consult in case someone else is trying out the same drug or reporting the same side effect... RANT, RANT, RANT.

So. Mexico. Si si! Margarita por favor! Hold the salt though (for health reasons, of course).