Pain is a pity, but really ...

I got a remarkably thoughtless comment from someone on the physician-driven site, crpsnews.org:

"Everyday is certainly a struggle for people with CRPS because they live in pain 24/7. While there is no cure for the disease, it can be slowed and likely to go into remission if treated early, ideally within three months of the first symptoms."

This remark was so fatuous and misguided that I found it alienating, but it raised several important issues that do come up -- especially in regard to people who mean well but don't know much about it (regardless of their educational level.)

Here are the main points of that remark:

1. Pain is why people with CRPS are to be pitied.
2. It's incurable, so don't go there.
3. It can be slowed or pushed into remission...
4. If you catch it really early.

Those of you who've followed me, know what's going through my head right now... "Where do I even start?"

Not with # 1. We'll have to come back to # 1. Let's go in reverse order.

4. "Diagnose it early, ideally within 3 months of first symptoms." Physicians control diagnosis; patients can only control how they respond to it. Since most cases of CRPS aren't even diagnosed for YEARS, that's not a useful remark. Say it at every medical workshop you go to; leave it out of a patient-driven site, because it's a slap in the face.

3. The remark on remission is slighly confusing.  Remission in CRPS is not like remission in cancer. It's a fragile state which can revert at any moment over the slightest thing. It's nothing like a cure. Remission is still possible years on, as the anecdotal evidence indicates.

2. A cure, as they pointed out, doesn't exist -- yet. And, with the wrong clinical focus and a hopeless clinical attitude towards a cure, it's no bloody wonder.

It can be cheaply prevented in ~80% of cases by 500 mg vitamin C, 3 times daily, for 2 weeks before and 3 months after surgery (or 3 months post-injury.) That's much more realistic than CRPS getting diagnosed within months, but so few people know about it that it doesn't happen much.

Result: lots of needless CRPS.

Spread the word about 500 mg vitamin C. It could save lives.

Most people who don't have CRPS focus on the pain as the reason for sympathy. Everybody has had pain, and the idea of pain is what they think they can identify with...
The pain of CRPS is like nothing else I ever experienced before. Yet I was an emergency nurse, motorcyclist, weightlifter, runner, horse rider, gymnast, martial artist... and a statistic, having endured more than one attempt on my life. (I've had an eventful life.) Plenty of opportunities to hurt; always recovered fast.


Yet, despite the often show-stopping pain I now live with, PAIN IS THE LEAST OF MY PROBLEMS. It's the weakness, autonomia, and cognitive decline that are the real problems.

That's where the research needs to be.

That's where the help is needed.

That, honestly, is where the most empathetic and useful sympathy lies :-)

Imagine feeling your ability to think, learn and remember simply dissolving, and there is nothing at all that you can do about it. You can hope it will come back to some degree, and eventually it does (if you avoid everything you're now sensitive or allergic to, eat tons of antioxidants and greens, drink lots of water, and don't screw up anything about your life at all -- while you can't remember what just happened, let alone all that you have to do...) but you know there are no guarantees, and after awhile, the repeated gapping starts to add up.

For a brain, that sucks, eh?

Doesn't that seem a bit more distressing than physical pain? I think so. It certainly has more of an effect on what I can do with my life.

Pain can be pushed through; the weakness, autonomia and cognitive decline are virtually impossible to push through.

Why is that? Because I need my muscles to be able to recover in order to rebuild melting muscles, my autonomic nervous system (ANS) needs to work well enough to let me regain control of my ANS, and I need my brain to work out how to help my brain.

It's like opening a box with the crowbar inside.

Relentless attention to activity, food and supplements, and state of mind are mandatory for a bearable life -- not because of the pain, but because of the weakness, autonomia and gradual brain-death. In order to barely stand my ground, I have to dance as fast as I can.

That's very hard for most people to wrap their heads around. It seems too hard. But to those of us with chronic CRPS, it's just another day. We have to manage all that and still somehow keep food in the house, laundry done, bills paid... relationships intact.


This focus on pain, to the exclusion of the more thoroughly disabling issues, has led to a serious misapplication of resources. A lot of lives have been damaged or destroyed because of that willful blindness in the medical and treatment domains. So it frustrates me, especially as a passing remark dispensed from a physician-driven site. (I wonder where their funding comes from... )

Sympathy is a lovely instinct, it really is, and I sure don't want to discourage it. Though I don't see sympathy in the remark I quoted above, I have heard people without CRPS express genuine sympathy in nearly identical terms. And they really do mean well. That matters!

There's a lot to be said for being sympathetic to someone's actual problems, which may not be exactly what you might expect. This would lead to more understanding, better connections to those who have it, more effective help, and in the end, to more effective care.

...

This morning, I woke up from a dream where I was running an international conference on CRPS, where 3/4 of the presentations were given by non-physicians: expert patients, massage therapists, PTs, acupuncturists -- you know, the people who really know about CRPS, and the stuff that really works for the real problems it causes.

In this dream, doctors could get a lot of CEUs, but they had to spend 60% of their time in non-physician workshops to get them. (How did I come up with 60%?) There was, how shall I put it, a certain amount of fussing about that...

It was a weird dream. Who knows, though, it could happen... It might do people like that staffer at crpsnews.org a world of good.

Proportional monocytes and CRPS, translated

Today's translation from medspeak to English: Inflammatory white blood cells and inflammatory nerve cells, in relation to CRPS.

Elevated blood levels of inflammatory monocytes (CD14+ CD16+ ) in patients with complex regional pain syndrome

Here's what the jargon means.
// ed. note: my comments and clarifications are picked out by those two slashes and the contraction for "editorial notation."

One important factor in CRPS is inflammation that starts in the nerves. Microglia and astrocytes, which are the inflammatory and immune cells of the nervous system, get active enough to cause worse pain by themselves.

That's a sparking astrocyte. Pretty, eh?

// ed. note:  The inflammatory and immune responses are mixed blessings throughout the body.  An immune response is uncomfortable; think about the last time you had the flu -- sucked, huh?  An inflammatory response can cause pain due solely to the inflammation, like with some kinds of arthritis.  So, for the microglia and astrocytes to make pain worse is not a surprise, since that's what immune response and inflammation can do anywhere.

One type of immune cells normally floating in your blood, called monocytes, can get into the brain and spinal cord and turn themselves into the nervous system's immune cells, microglia. The added level of inflammatory/immune response leads to more pain.

// ed. note: Again, not as strange as it sounds.  The body's living cells all contain complete DNA, and they are designed to be both helpful and appropriate; heart cells transplanted into muscles become muscle cells, and muscle cells transplanted in the heart become very much like heart cells.  So, for this type of small white blood cells to turn into microglia is reasonable.

These are microglia in various active states.

// ed. note: The inflammatory response releases cytokines.  Cytokines are the chemical widgets, produced in inflammation, that serve as the chemical messengers running around the cells screaming that the sky is falling.  Some cytokines increase inflammatory pain, some cytokines reduce it.

This study looked for particular kinds of inflammatory monocytes in the blood, to test the assumption that higher levels of these particular types of monocytes (which can then turn into microglia, making the inflammation and pain worse, etc.) are related specifically to CRPS.

Now here's the fun part.  The basic blood-borne indicators of inflammation and illness were no different in those with CRPS than in normal people. That's why conventional lab results, like "complete" blood counts, come back normal for us.  However, the proportion of the particular types of monocytes associated with CRPS, were significantly higher in those with CRPS.  The type of cytokine that reduces inflammatory pain, was also significantly lower in people with CRPS.

That means the inflammatory process screws us coming and going, and screws specifically us, the people with CRPS, in ways that can be checked in a lab.

OK, GTK.

These are sensible scientists: they state that they don't know if the monocyte proportions changed before or after the onset of CRPS, or both before and after.  If before, it might indicate a predisposition to CRPS, in which case surgeries and accidents have to be handled with specific care for antioxidant therapy and aggressive pain control. If after, it might be relevant in figuring out how things are going and if what the doc is doing works.

Also, some drug company could make a staggering fortune off of new meds that mess with this process. They actually mention that at the end of the article, which means someone has to fund their work.

// ed. note: Be fair. We have a profit-based health care system driven by enormous corporations that are traded on the stock exchange, and the Sarbanes-Oxley laws mean that their first obligation is to their shareholders. Not patients. Not customers. But shareholders.

Conventional medicine has to come back to profitability.  There are more direct ways to address these immune and inflammatory issues by existing means, which could be further developed, but they don't sustain the pharma industry's usual annual returns of 20-40% -- a rate of stock profitability matched only by oil companies.

... On your pain.

If you have something to say about that, you can contact your political representatives here: http://www.usa.gov/Contact/Elected.shtml

Putting the "con" in mitochondria, the "funk" in dysfunction

Mitochondria (from the Greek, meaning "string grain" -- yeah, it's lame, but it sounds good in Greek) are independent little one-celled organisms that live inside your cells and make energy for them. If you ever studied the ATP cycle (also called the Krebbs cycle or the citric acid cycle, depending on where you went to school and how deeply they went into it), then you should know that this is where the ATP cycle takes place.

Without mitochondria, you have no way of converting food into energy.

When you were being conceived, half your cells' genes came from your mother and half from your father. All of the other stuff that goes inside a cell came from your mother. This includes the mitochondria. (This is why mitochondrial DNA is used to track maternal inheritance: it always comes down the female line.) Your mother's cell hosts conception, just as (normally) your mother's body hosts gestation.

Mitochondria have a fairly smooth outer layer and a deeply-rumpled inner layer. Most of the action happens inside the rumpled layer. This is where the ribosomes, most of the fluids and loose protein, and the ATP-making particles hang out.

Cells, including mitochondria, need various proteins to do their work with. Large proteins get carefully handed from the outside world, through the outer layer of the mitochondrion (singular of "mitochondria" -- sorry, it's still Greek), then into the inner layer.

If the smooth outer layer is damaged, this makes this transfer process screw up, and the inner layer gets disrupted, ripping up the cell. Granules and nucleic acids all over the place. Bang goes that ATP production.

Those are some busted mitochondria.

This kind of damage happens in response to certain kinds of toxins (including certain medications for AIDS and all psychoactives -- including antidepressants and pain medications, which seems especially mean!), occasionally from genetic disturbance, and occasionally as a consequence of illness -- or nerve injury and its complications.

Mitochondrial dysfunction has been repeatedly and profoundly linked to neurogenerative diseases like Alzheimer's and Parkinson's; cell-metabolism problems like heart disease, insulin resistance and type II diabetes; and several diseases often mistaken for CRPS.

Not surprisingly, symptoms of mitochondrial dysfunction are the worst in tissues that use the most energy and have the largest number of mitochondria per cell: nerves, muscles, brain.

Recently, it has been strongly associated with CRPS. And the cherry on top: it plays a vital role in neuroplasticity, or the way your nerves and brain change -- for better or worse.

Hell-o, "pain-brain." We thought we knew ya!

Knowing why it's so damnably exhausting to walk a mile, when it used to be fun -- fun! -- to run 3, is a bit of a relief. First question that leaps to my mind: How do I fix 'em? How do I give them what they need to get better and protect themselves?  The answer seems simple: antioxidants are what's needed to prevent and repair that damage (good explanation of that here) to the walls of the mitochondrial cell.  Mitochondria are both the biggest makers of reactive oxygen species and the biggest scavengers of them, so of course it makes sense that that's exactly the kind of help they need when they can't keep up.

Downing antioxidants by the bucketful is one way to get them in. Intriguing for three reasons:

• Taking moderate amounts of the antioxidant Vitamin C after surgery hugely reduces your chances of getting CRPS. (Upper limb and lower limb surgeries were studied.)
• There's some indication that Vitamin K may help combat the progress of CRPS.
• Taking antioxidants is pretty easy: delicious food, accessible pills, not bad.

Kind of depressing for one simple reason: it's iffy whether, once you've got the disease process going, the antioxidants can get where they're needed and save your poor beleaguered mitochondria. ... Having said that, I notice that the writers of that article seem to be trying to sell something, and that makes me very suspicious of their conclusions.

Next, I'll offer suggestions for patients, suggestions for clinicians, and then wind this up with a foray into the question of whether mitochondrial issues have a genetic component, like being X-linked -- the way a cat's fur color is! 

For people with CRPS -- So what is a poor, confused CRPSer to do?

Two things that you hardly need reminding of:

1. Trust your sense of your own body.
2. Do what works for you.

Most antioxidants are not going to hurt you, without letting you know first (that is, make you nauseous or feel funny.) Take vitamin C in doses no larger than 500mg, since larger doses tend to trigger your gut to throw the C away. Go ahead and try stress-vitamins, co-enzyme Q-10, N-acetylcysteine, hair-skin-&-nails vitamins (these are really fat-soluble antioxidants) ... try things, take what helps, and put aside the rest if they don't do anything. Keep in mind that things change: what doesn't work now might work later, and vice-versa.

Also, eat all the leafy greens you can get: seaweed snacks, Mom's collard greens, kale krunchies, spinach salad, you name it. It's amazing nerve food.

For antioxidant powerhouses, look for dark-red and dark-blue fruits: pomegranates, blueberries, red wine, chocolate (though some CRPS people have to avoid that for its nerve effects), mangosteen (my favorite fruit), cranberries, and so on.

Stay smart. Stay loose. Keep going.

For medical people -- clinical takeaways:

Most treatment standards, particularly for CRPS, are based on science that's over a decade old. They shouldn't be changed blithely but they can certainly be improved. There is plenty of room for that.

The following points are intended as additions to the standards you follow for CRPS, as they are good guidelines for mitochondrial and neurologic support in a system compromised by CRPS.

•  After any limb surgery, give Vitamin C 500 mg, QD or BID, for a couple weeks beforehand and 30-50 days after -- or to metabolic tolerance, if that's too much. Use a food-associated form for best uptake. This one intervention will reduce the risk of developing CRPS by 80%, according to the best current data.
•  We assume your patients are taking an adequate multivitamin and are eating plenty of greens, dark fruits, and wholesome proteins. So make sure they are.  Direct them to food bank, food stamps or other food assistance as needed. Give recipes. (No kidding.)  2 benefits: better antioxidant uptake if taken with antioxidant-rich food, and increasing the patient's own sense of agency/participation improves pain and affect.  (If you don't believe in multivitamins, then get out of the supermarket/pharmacy and get some real ones.)
•  Stress the antioxidant vitamins.  In acute CRPS, give water-soluble antioxidant vitamins in 1-3x the doses you'd give a healthy person.  Give fat-soluble antioxidants (A, D, E) up to 2x normal, testing levels as indicated.  Consider vitamin K inj.
•  In cold/chronic CRPS, give water-soluble antioxidant vitamins in 3-5x the doses you'd give a healthy person (start at 2x and work up).  Give fat-soluble antioxidants (A, D, E) up to 2-4x normal, testing levels as indicated; consider weekly mega-dose D (as used in AIDS.)  Give vitamin K inj.  Check serum or urine levels as indicated, especially as we develop absorption disorders.
•  Give "uber-antioxidants" like ubiquinone (co-Q 10), N-acetylcysteine, or glutathione. There are indications that these can provide substantial benefit -- though again, not normally curative of chronic CRPS. They are impressive, especially for mitochondrial-dysfunction issues.

These ranges are empirical; if you can find the funding to do the science to develop more reliable ranges for this population, so much the better.

Adequate tissue oxygenation and perfusion can return substantial function and significantly reduce pharmacologic burden. Patients can demonstrate this, even where the data have not been published and peer reviewed. Therefore, use antioxidants rigorously and intelligently.

Image credit: http://www.vrp.com/antioxidants/-r-lipoic-acid-unique-mitochondrial-antioxidant-fights-premature-aging.  (Article's not bad.)

Why all that anti-oxidation when the medical literature is not definitive?  2 reasons, which you ought to know for yourselves:

1. Between the cortisol and systemic oxidative stresses, it can't hurt and it will help something. You'll see a distinct improvement in affect, activity, motivation and well-being when the dose is optimized, even if it can't be expected to be curative.  Making your patient's life more bearable is an essential part of your job.
2. Let's say this together, everyone: statistics mean nothing in the case of the individual.  Accepted, standardized medicine is what you start with, but, when your case is taking you out to the margins, you go to the margins, because that's where your success is most likely to await.  

Keep in mind that doctors are not the only scientists interested in the human body.  Be prepared to look into other disciplines for leads when your own offers no good options.

Try Nursing, PT, Nutrition, Therapeutic Massage -- you'll realize that nobody knows more about soft tissue's functional physiology in vivo than therapeutic massage science, and if nothing else, the exercise in intellectual flexibility might do you good.

The accepted style is very different, but the info they have is tremendous.

Forward-looking thoughts:

• Consider infusing vitamin K into CRPS-damaged tissues. I would love to see studies on that.
• Figure out how to deliver antioxidants in a targeted way. (Now! Please!) This would be a good way to save a lot of lives and end tons of misery.

... And for all curious people ...

Let's go back to mitochondria in reproduction. Kind of in an X-rated way, figuratively speaking.

We know that women have two X chromosomes. The Y chromosome is a stubby little object with hardly any data to use, unless you're into color-blindness or hemophilia; this means women have quantities of extra data, which can have even more devastating effects (as in, Down syndrome.) So how to handle the extra genes?

Pick one. Simple as that.

Shortly after conception, when the cells are just dividing like mad and haven't decided what to be yet, every single cell turns off one of its two X chromosomes; each of that cell's daughter cells inactivates the same X chromosome. As the cells continue to multiply, then fill out, fold, bend around, and specialize, to become a whole, separate being, it means that X-linked traits appear in a mottled pattern throughout the body, as the two sets of daughter cells continue reproducing and passing on their particular X-activations.  Isn't that curious?

As an especially decorative instance, cats' hair color is an X-linked trait:


Cool, huh? Love her accent, too.

But this fact brings me to a serious question about mitochondrial disease. If mitochondria are sex-linked, is there a relationship between the X chromosome and mitochondrial expression? It seems improbable that there wouldn't be, because mitochondria reside inside the cell, and the cell's action is determined by the genes within it. The mitochondria had to have developed a special relationship with the X's in the 23rd chromosomal pair, after all those millenia.

It's generally accepted that mitochondrial diseases are due to toxification or to complex, multigenetic issues. Ok, fine. But what about mitochondrial vulnerabilities that don't become pathologic until they are damaged in some other way? To what degree is toxification an issue related to X-activation? In other words, is mitochnodrial vulnerability related to vulnerabilities in the active X chromosome?

Is there a patchy characteristic to the early stages of mitochondrial destruction? -- You know, the early stages of rare disorders, the time when it's impossible to get a diagnosis because the doctors are all so busy chasing their own tails around your irrational symptoms and their own ignorance.

Is that initial "mottled" activity one reason why these diseases are so damn weird?

Link list:

Wikipedia's entry on mitochondria is pretty good:
http://en.wikipedia.org/wiki/Mitochondria

On mitochondria and AIDS meds:
http://www.ncbi.nlm.nih.gov/pubmed/20818734
On mitochondria and pyschoactives:
http://www.ncbi.nlm.nih.gov/pubmed/18626887

Alzheimer's Foundation:
http://www.alzfdn.org

Michael J. Fox's Parkinson's foundation:
http://www.michaeljfox.org/

United Mitochondrial Disease Foundation, listing diseases which are often mistaken for CRPS:
http://www.umdf.org/

Mitochondria and neuroplasticity:
http://www.ncbi.nlm.nih.gov/pubmed/20957078

A good rundown (so to speak) of antioxidants' function:
http://www.ionizedwateronline.com/Antioxidants.html

Vitamin C around surgery.
Upper limb:
http://www.ncbi.nlm.nih.gov/pubmed/17606778
http://www.ncbi.nlm.nih.gov/pubmed/20224742
Lower limb:
http://www.ncbi.nlm.nih.gov/pubmed/19840748

Vitamin K and CRPS progression:
http://www.ncbi.nlm.nih.gov/pubmed/20378261

Getting antioxidants where they're most needed. Ignore the shystering towards the end:
http://www.ncbi.nlm.nih.gov/pubmed/21422516

ALA and regeneration of Vitamin E:
http://www.vrp.com/antioxidants/-r-lipoic-acid-unique-mitochondrial-antioxidant-fights-premature-aging