[fmichael]

Jim Broatch of the RSDSA has just forwarded a press release about a new article by Vania Apkarian, whom older redears will recall as the author of "Chronic back pain is associated with decreased prefrontal and thalamic gray matter density," J Neurosci. 2004 Nov 17;24(46):10410-5 [free full text at http://www.jneurosci.org/cgi/content...urcetype=HWCIT

In any event Dr. Apkarian's new research is as exciting as the last round was disturbing, and once again features our old "friends" the NMDA receptors:

CHRONIC PAIN LINKED TO OLD MEMORIES

Scientists have found that a key source of chronic pain appears to be an old memory trace stuck in the prefrontal cortex. With new understanding of the pain source, Vania Apkarian, professor of physiology, and of anesthesiology, at Northwestern University's Feinberg School of Medicine (USA), has identified a drug that controls persistent nerve pain by targeting the part of the brain that experiences the emotional suffering of pain. The drug is D-Cycloserine, which has been used to treat phobic behaviour over the past decade. In animal studies, D-Cycloserine appeared to significantly diminish the emotional suffering from pain as well as reduce the sensitivity of the formerly injured site. It also controlled nerve pain resulting from chemotherapy, noted Apkarian, who is a member of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. The drug has long-term benefits. Animals appeared to be pain free 30 days after the last dose of a 30-day regime of D-Cycloserine. "In some ways, you can think of chronic pain as the inability to turn off the memory of the pain," Apkarian said. "What's exciting is that we now may be relieving what has clinically been the most difficult to treat - the suffering or the emotional component of pain." Scientists have always tried to understand pain from the viewpoint of sensation, Apkarian said. "To control it, they tried to stop the sensory input to the brain. "We are saying there's a cognitive memory and emotional component in the brain that seems abnormal. Easing that may have a bigger effect on suffering." Chronic pain is not caused by a single mechanism, Apkarian noted. Sensory abnormalities in people with chronic pain probably drive this memory abnormality. One of Apkarian's studies with rats tried to separately measure their emotional suffering and their physical pain after being treated with the drug (The rats had chronic pain from a healed limb injury). The results indicated the animals' emotional suffering decreased much more than their physical pain. While the physical pain appeared to be reduced 30 per cent - their emotional suffering completely disappeared. Based on the animal results, the next step will be to test the drug in clinical trials, Apkarian said. When we do this in a clinical trial, we expect people to say I still have the pain, but it's not bothering me anymore," Apkarian said. "We think they will have a physical awareness of the pain, but its emotional consequences will have decreased." He said the drug potentially may lower the amount of standard analgesics people have to use. In Apkarian's previous study, published in late 2006, he revealed that chronic back pain appears in a different part of the brain than the discomfort of burning your finger, for example. With a functional MRI, he found that chronic back pain shows up in the prefrontal cortex. By contrast, the acute sensory pain of the burned finger appears in the sensory part of the thalamus. Apkarian also found that the longer a person has been suffering from chronic pain, the more activity in the prefrontal cortex. He was able to predict the years of their suffering from the MRI. It's cumulative memory," he explained. "I can predict with 90 per cent accuracy how many years they have been living in that pain without even asking them the question."

The study will be published online in Pain: The Journal of the International Association for the Study of Pain

This appears to be the abstract for the article in question:

Pain. 2007 Apr 19
d-Cycloserine reduces neuropathic pain behavior through limbic NMDA-mediated circuitry.Millecamps M, Centeno MV, Berra HH, Rudick CN, Lavarello S, Tkatch T, Apkarian AV.
Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave., Chicago, IL 60611, United States.

Human brain imaging studies suggest that chronic neuropathic pain has a strong emotional component that is mediated by medial prefrontal cortex (mPFC) activity; in rodents, the mPFC is involved in emotional and cognitive aspects of behavior, including the extinction of Pavlovian fear conditioning. Together, these findings suggest that the cortex may modulate the memory trace of pain. As d-cycloserine (DCS), a partial agonist of the NMDA receptor, can enhance learning and potentiate the extinction of acquired fear, in the present study we tested its efficacy in neuropathic pain behavior. In rats with spared nerve injury (SNI), repeated daily oral administration of DCS reduced mechanical sensitivity of the injured limb in a dose-dependent manner; this effect continued for weeks after the cessation of DCS treatment. In addition, re-exposure to DCS further enhanced antinociceptive behavior. Repeated oral DCS administration also reduced cancer chemotherapy drug-induced neuropathic pain behavior. Infusions of DCS directly into the mPFC (especially within prelimbic cortex) or the amygdala (but not into thalamus, insula, or occipital cortex) acutely induced antinociception in SNI rats. The antinociceptive effect of intra-mPFC DCS infusions was mimicked by NMDA and glycine, and blocked by HA 966. In the mPFC of SNI rats, NR2B expression was down-regulated; however, this effect was reversed with repeated oral DCS. Lastly, infusions of DCS into mPFC reversed place avoidance behavior induced by mechanical stimulation of the injured paw in SNI rats. These findings indicate that limbic NMDA-mediated circuitry is involved in long-term reduction in neuropathic pain behavior.

PMID: 17449176

I will try and post a copy if I can get my hands on it.

Mike

[betsyherm]

I don't know about anyone else (any of the other teens and young adults on the board), but I'm not old enough to actually have "old" memories. I certainly wasn't before I got RSD at the age of 12!

Really, this doesn't sound very promising. I'd rather they actually treat the pain than the "emotional effects." Really, it's just another way of trying to make it seem like we're all just crazy people who let some pain take hold of our lives, which is not true.

So, I'm pretty much rewriting this...I reacted very badly to my first read-through because it seemed at first like the old "it's all in your head" routine. It's not quite that, but it's not particularly helpful either.

Sorry to anyone who read what I wrote first! Perhaps all those years of doctors telling me I was crazy have made me a little angrier than I like to let on.

[fmichael]

Dear Betsy -

Not to worry. The relationship between pain and suffering is as important as it is sometimes difficult. Pain, physical and/or psychological is to an extent unavoidable in life. Suffering is not.

Essentially "suffering" - as opposed to pain - is caused by attachments to the way things used to be or aversions to the way they are. Cut those out of the picture, and the pain alone is a lot easier to tolerate. If there's now going to be a drug of all things that can help in the process, that may be terrific. In the meantime, we have the mindfulness practice of meditation and teachers like Jon Kabat-Zinn, whose Mindfulness Based Stress Reduction program has given countless pain patients, including myself, a real lifeline out of the morass of chronic pain.

My meditation teacher, Shinzen Young expresses it this way:

Suffering = Pain x Resistance

For a copy of one of his essays on the subject, "A Pain-Processing Algorithm," click here:http://shinzen.org/shinsub3/artPainP...gAlgorithm.pdf. I would urge you to give it a look. (For anyone whose interested, Shinzen's book and accompanying CD "BREAK THROUGH PAIN: A Step-by-Step Mindfulness Meditation Program for Transforming Chronic and Acute Pain" (2005) - which a number of people in this little group have found helpful - is available either through his website or the publisher, Sounds True.)

These are concepts that have been around for a long time, and are really, if I may be forgiven, at the heart of Buddhism. "I teach suffering, its origin, cessation and path. That's all I teach", declared the Buddha 2500 years ago. For four very good audio clips on the subject, by some serious teachers, each around 13 minutes long, I would invite you to open a BBC page on Religion & Ethics - Buddhism/The Four Noble Truths. http://www.bbc.co.uk/religion/religi...letruths.shtml In particular, the pieces by Stephen Batchelor and Robert Thurman are simultaneously accessible and profound.

Enjoy!

Mike

p.s. And good luck on the move to NC.

[Imahotep]

Exciting news, indeed.

It's been around for many years and is used for other disorders as well. It sounds great for me. I'll be talking to my doc.

[Vicc]

I just told a good friend that I seem incapable of initiating anything; that I can react, but otherwise the fires inside seem to have gone out. Well, I reacted to this press release, but before I comment about it, I would like to see what the journal article actually says. but the link didn't take me there.

I'd appreciate it if someone would let me know if it worked for them. If it did, I'll find another way to see the article, but if not: Mike, try again...Vic

[betsyherm]

Thanks, Mike. That actually explains a lot. It makes sense in my personal life as well as in general. I guess that I feel that I'm not really suffering right now. I have RSD and pain and problems using my leg in general, but this has been more than half of my life, and it's just something to try to minimize. That's not something that's come easily to me, and I think it must be even harder if someone is living an adult life and it suddenly ends. I've just had to learn to mold my life to my physical abilities, because nothing is set at the age of 12.

Off to bed now! Thanks for the article and your response!

-Betsy

[theoneRogue420]

Hi Betsy You may be young, but you are certainly wise beyond your years.

I agree with you completely. I have a health condition I have had my whole life, which doesn't bother me at all, it's just "a part of me". As you grow, you learn to adjust and compensate... it's much easier as a child/teen.

But I was 30 when I got hurt, and 31 when I had the surgery and ended up with rsd. I had a husband out to sea (6 month long westpac) and two sons to raise on my own. I was doing a fine job of it, until this happened.

Overnight, my whole world changed. I had been dealing with the injury for almost a year at this point, and was looking forward to the surgery and getting on with my life. That never happened, of course. As of now, I have had rsd for 14 years.

Just about the hardest part for me was the "used to be's"... I used to be able to do this, I used to be able to do that. My sons didn't understand why Mom couldn't go beachcombing anymore, or run around at night chasing lightning bugs (depended on where we were living, lol), whatever. Mom didn't cook like she used to, there was a LOT more fast-food in our lives.

My getting rsd didn't affect just me, that I could have handled better. But I will never get over what it did to my son's lives, and their relationships with me.

[fmichael]

Can't sleep, even with lots of oxycodone, so a couple of quick points. First to Vic, I've come up with what should be a stable link to the 2004 Apkarian article, and revised my initial post accordingly. Hopefully (1) it will work and (2) I'll be able to get a copy of the new article in short order.

Now to Betsy. I cannot begin to imagine the strength of character that's required to go through this at your age. I have two sons, the oldest is 14 and he's adapted to a lot of health problems over the years, but nothing as significant as RSD! I join Rogue in commending you on your openness and presence of mind.

I guess the good news is that while having good coping/equanimity skills can't hurt at any age, it is my understanding that young people have a much better prognosis with this disease, translating into a much higher chance for successful recoveries, either spontaneously or through medical therapies.

And while this is admittedly "off topic," I have it on good authority that - to be specific - the younger you are, the greater the probability that a trip to Germany would produce a successful outcome. If you haven't seen it, I would urge you and your parents to take a look at a short article written for people without any medical background called "Overview of Ketamine Infusion Therapy," by Philip Getson, DO which is posted on the Reflex Sympathetic Dystrophy Syndrome Assn. webpage at http://www.rsds.org/3/treatment/ketamine.html You're in my heart kid.

Mike

[Hippyhair]

Poor rats! But, I am wondering how they monitor the pain that the rats feel? And, if they can monitor that, why can't they do the same for humans? We (RSD'ers) might seem healthy on the outside, suffering on the inside. The rat's aren't able to voice their pain on a scale, or tell their Researchers that the pain has travelled, or changed from zappy pains to deep aching pains. How do the researchers know that? Or, am I just not able to understand the whole concept, and missed the point altogether....hee hee....(most likely scenario!)
Hippy

Hi Everybody,

I wish the rats could talk. Roz