Wouldn't stem cells help with pain?

[Aquitaine]

Because of the effect that my pain doctor has had when injecting steroids into my spine on the neuropathic pain in my foot, wouldn't it make sense that injecting stem cells into the bruised area of my cord might help (at least) with the pain. And even possibly return sensation and movement to my lower extremities? At 48 am I just too old for this therapy to be effective? Does this therapy need more testing before that much improvement might occur? I'm just trying to understand, I know stem cell research is going to help (or already is helping) with sensation/movement/etc. improvement, but are we also expecting the healing process that provides, to help relieve this #*&^$*! pain?

Questions, questions, annoyin'... ain't I? http://sci.rutgers.edu/forum/images/smilies/biggrin.gif

[dejerine]

Dear Aquitaine,

I think the fact that severe chronic pain is worse than our motor deficits is not a concept that has reached the public, nor the medical profession. Great pity is afforded those with motor loss, but confusion and disinterest confronts those with Central pain. I have many people kindly assist me getting in and out of buildings, but there is almost no interest in allowing me to wear abbreviated clothing so I can go into public.

The eye controls what people feel or believe, and no eye can see central pain. They can see me having difficulty with a door, and to the public's credit they are always generous with what they know about or can see for themselves.

Unfortunately, I think many of the scientists who do motor work do not study and do not know about central pain. Since we do not know the absolute cause of central pain, we cannot be sure, but since CP is presumably due to the altered protein production in injured neurons (such that abnormal ion channels are produced, but the inhibitory switch involving chloride is lost because there is inadequte protein carrier for chloride to move to the cell membrane (ie. not enough KCC2 being manufactured) presumably normal cells implanted WOULD produce normal proteins would not cause NEW central pain and possibly may reduce the impact of existing injured neurons. The brain is plastic (or can change) so presumably the brain would come to prefer the cells sending normal signals. Also, new signal coming to brain should allow it to do whatever the brain does to shut off pain, but we don't know what it is that the brain does to inhibit pain. All agree that the manufacture of GABA is central to pain inhibition, but there is much work to be done in understanding how that happens.

Science is so blind to pain. David did everyone here a service in gathering the pain descriptor database which was published by IASP. All of you who have filled out the survey at painonline.com are also doing your part to educate the medical profession.

The real answer is that pain is not a concern of those seeking to restore motor function. The two groups publish in different journals, speak of different chemical pathways, and rarely associate in research with one another.

Pain is the stepchild's stepchild in medicine. That is why it was so noble of Christopher Reeves to fund Bryan Hains work at Yale, which uncovered the Nav1.3 ion channel as causing Central Pain, even though Reeves does not have Central Pain, according to his own descriptions. This fact makes Reeves above generous in his viewpoint.

If I had only motor deficits, I dont' know that I could spend precious research dollars on pain. It shows he is a bigger man than most that he would reach out to others, when his own need is so great. These people are so godly I don't know how they do it.

[dejerine]

Dear Aquitaine,

I think the fact that severe chronic pain is worse than our motor deficits is not a concept that has reached the public, nor the medical profession. Great pity is afforded those with motor loss, but confusion and disinterest confronts those with Central pain. I have many people kindly assist me getting in and out of buildings, but there is almost no tolerance for allowing me to wear abbreviated clothing so I can go into public places, including the courts.

The eye controls what people feel or believe, and no eye can see central pain. They can see me having difficulty with a door, and to the public's credit they are always generous with what they know about or can see for themselves.

Unfortunately, I think many of the scientists who do motor work do not study and do not know about central pain. Since we do not know the absolute cause of central pain, we cannot be sure, but since CP is presumably due to the altered protein production in injured neurons (such that abnormal ion channels are produced, but the inhibitory switch involving chloride is lost because there is inadequte protein carrier to move chloride to the cell membrane (ie. not enough KCC2 being manufactured).

Presumably, normal cells implanted WOULD produce normal proteins and would not cause NEW central pain, and possibly may reduce the impact of existing injured neurons. The brain is plastic (or can change) and presumably the brain would come to prefer the cells sending normal signal.

Also, new signal coming to brain should allow it to do whatever the brain does to shut off pain, but we don't know what it is that the brain does to inhibit pain. All agree that the manufacture of GABA is central to pain inhibition, but there is much work to be done in understanding how that happens.

Science is so blind to pain. David did everyone here a service in gathering the pain descriptor database which was published by IASP. All of you who have filled out the survey at painonline.com are also doing your part to educate the medical profession.

The real answer is that pain is not a concern of those seeking to restore motor function. The two groups publish in different journals, speak of different chemical pathways, and rarely associate in research with one another.

Pain is the stepchild's stepchild in medicine. That is why it was so noble of Christopher Reeves to fund Bryan Hains work at Yale, which uncovered the Nav1.3 ion channel as causing Central Pain, even though Reeves does not have Central Pain, according to his own descriptions. This fact makes Reeves above generous in his viewpoint.

If I had ONLY motor deficits, I dont' know that I could bring myself to spend precious research dollars on pain. It shows Reeve's is a bigger man than most, a giant really, that he would reach out to others, when his own need is so great. Such people are so godly I don't know how they do it.[/QUOTE]

[Aquitaine]

Hi Dejerine,

Is there an editor that you could use to write posts, then ctrl+a to select it, ctrl+c to copy it, then ctrl+v to paste it into this forum's Post A Reply edit box? And would that editor be easier or harder for you to use? I've had the problem of duplicate posts when writing long replies with this forum. I talked with Wise and Jeff and I think this will be a hard bug to fix, so both Wise and I do all our long posts in another editor now, for me the best editor is notepad (comes up fast, uses little memory, etc.). Is this a possibility for you, or would using another editor and doing the cut and paste make it a lot harder? I brought this up in your "adenosine" post, but I'm not sure if you saw it or not. BTW: I put in my own mug for my avatar now, now you can see why I picked the fake one, was closest I found http://sci.rutgers.edu/forum/images/smilies/smile.gif.

Thanks for your reply to the stem cell questions, extremely helpful as usual. I know pain is low man on the totem pole of medicine, I've been dealing with that for a pathetically long time. From time to time I find an amazing doctor who goes far out of his way to help me, but far too often I've found myself in an ER gripping the rails of a hospital gurney, screaming for somebody to either cut off my legs or shoot me. But I saw that special on TV (its recorded over in the CURE forum) and it just seemed to me that, even if I didn't get any improvement in movement or sensory ability, maybe the stem cells would help with this pain, maybe even just the removel of scar tissue (which the surgeon felt may be attributable to some of the shown improvments) would provide some relief. Was just wondering how remotely possible that might be, so I'll try to hold on to some hope for that to happen whenever the FDA gives its blessings for it to be done here http://sci.rutgers.edu/forum/images/smilies/wink.gif.

http://sci.rutgers.edu/forum/images/smilies/mad.gif...but don't get me started on the FDA though, I've worked for drug companies developing medical devices and had to write volumes to meet all their red tape (if you've never been involved in writing these software protocols you probably think that sounds pretty reasonable, unfortunately you have no idea how much of a waste of time most of this is, for one product change we would have to produce and average size bookshelf worth of paper, and that was just for the software). If you've ever wondered why it takes so long to get a drug or device released for use by the public, or why it costs so much (although the companies pile on for their pound of flesh), just take a look through the FDA regs, if you have a couple months of free timehttp://sci.rutgers.edu/forum/images/smilies/rolleyes.gif.

[dejerine]

Aquitaine,

Thanks for the advice on notepad. I will try that method.

The olfactory bud cells are not true stem cells, but they retain enough potential for change to turn into neurons, hence they are stem cells. The restoration of motor function is not perfect. They stand or move with difficulty. Still, it is a wonderful thing.

For years, we have tried to find pain as an injury in the cord or brain, which had three axes. The x,y,and z dimensions. This would explain why all CP patients are not the same. For example, in me, a cold room causes a terrible burn--Alan says ambient temperature is not a factor in his pain.

Pain receptors themselves vary, some respond to powerful stimulus only, others can respond to weak stimulus. Receptors may respond to mechanical, thermal, or chemo stimuli. There is some evidence that for highly sensitized neurons (Bad CP is as sensitized as you get), what is normally a mechoreceptor can act as a chemoreceptor.

The problem with being sure about what to expect from stem cells, is that we are unsure how to specify what the stem cell will do. It does its own thing.


Prevailing view now does not so much hunt for an anatomical target for the pain, as for a genetic target. Each of us inherits varying amounts and types of NMDH receptors, calcium channels, kinase amounts and proportions, etc. This means those of us with CP may have a genetic predispostion to have it.

This predisposition likely pertains to protein kinase C group or even protein kinase A group, since knockout rats which lack these kinases CANNOT be made to get CP.

So the real answers may be buried in our genome. Infection with viruses instilled with needed DNA may give us the needed proteins, but cells express new DNA only when they are dividing and the average cells lasts five years. So while we are waiting for our DNA to be remade, we need less sophisticated remedies, such as adenosine enhancers, blockers of protein kinase C gamma, blocking of glutamate receptors, etc.

Using stem cells to bridge injured areas of the cord would work if we were sophisticated about how to do it, but that could take years. Right now, some pharmacological block is needed.

Our injured neurons will continue to make FETAL Nav 1.3 channels (this is a genetic alteration in CP) and our cells will continue to lack a protein carrier for chloride, turning ordinary inhibition signal into excitation. Eventually a bona fide cure will be developed, but in the meantime, some sort of cone toxin, or chemical will give us blessed relief.

In short, the whole thing is very doable, but the government must make it a priority, since the brainos of the biological world need a real job to choose pain research. There are many PhD's who do work on pain under a postdoctoral grant, but these jobs are temporary, and lack benefits, so they have to leave--a terrble waste. Other scientific endeavors, which have a reliable employment future, continue to draw the smart guys.

[dejerine]

Originally posted by dejerine:

Aquitaine,

Thanks for the advice on notepad. I will try that method.

The olfactory bud cells are not true stem cells, but they retain enough potential for change to turn into neurons, hence they are stem cells. The restoration of motor function is not perfect. They stand or move with difficulty. Still, it is a wonderful thing.

For years, we have tried to find pain as an injury in the cord or brain, which had three axes. The x,y,and z dimensions. This would explain why all CP patients are not the same. For example, in me, a cold room causes a terrible burn--Alan says ambient temperature is not a factor in his pain. Yet, we both cannot stand the touch of clothing.

Pain receptors themselves vary, some respond to powerful stimulus only, others can respond to weak stimulus. Receptors may respond to mechanical, thermal, or chemo stimuli. There is some evidence that for highly sensitized neurons (Bad CP is as sensitized as you get), what is normally a mechoreceptor can act as a chemoreceptor.

The problem with being sure about what to expect from stem cells, is that we are unsure how to specify what the stem cell will do. It does its own thing.


Prevailing view now does not so much hunt for an anatomical target for the pain, as for a genetic target. Each of us inherits varying amounts and types of NMDH receptors, calcium channels, kinase amounts and proportions, etc. This means those of us with CP may have a genetic predispostion to have it.

This predisposition likely pertains to protein kinase C group or even protein kinase A group, since knockout rats which lack these kinases CANNOT be made to get CP.

So the real answers may be buried in our genome. Infection with viruses instilled with needed DNA may give us the needed proteins, but cells express new DNA only when they are dividing and the average cells lasts five years. So while we are waiting for our DNA to be remade, we need less sophisticated remedies, such as adenosine enhancers, blockers of protein kinase C gamma, blocking of glutamate receptors, etc.

Using stem cells to bridge injured areas of the cord would work if we were sophisticated about how to do it, but that could take years. Right now, some pharmacological block is needed.

Our injured neurons will continue to make FETAL Nav 1.3 channels (this is a genetic alteration in CP) and our cells will continue to lack a protein carrier for chloride, turning ordinary inhibition signal into excitation. Eventually a bona fide cure will be developed, but in the meantime, some sort of cone toxin, or chemical will give us blessed relief.

In short, the whole thing is very doable, but the government must make it a priority, since the brainos of the biological world need a real job to choose pain research. There are many PhD's who do work on pain under a postdoctoral grant, but these jobs are temporary, and lack benefits, so they have to leave--a terrble waste. Other scientific endeavors, which have a reliable employment future, continue to draw the smart guys.

[alan]

Pain is low priority because it's invisible. Other conditions can be seen with the naked eye, via x-ray or MRI, or via lab tests. Pain can't - there's only the patient's word that it exists, and how bad it is.

Alan

"Was it over when the Germans bombed Pearl Harbor?"

[Aquitaine]

Hi Dejerine,

There are things in your post that I understand, and things that I don't. <sigh> chemistry was never my strong suit, how I ever managed to get through high school is still a mystery, let alone college http://sci.rutgers.edu/forum/images/smilies/biggrin.gif. But I think what your saying, is "we need sumpin in da meantime", right? And that the stem cell implants MAY work, but its rebuilding of the DNA for relieving the CP could take a very long time, based on the kinds of improvements seen by this therapy so far. Don't know how good or bad a summary that is, your words speak for themselves as always, but I agree with and understand your end points completely. We definitely need to get increased funding for this field.

John