RSD/CRPS, Multiple Sclerosis, LDN & Ketamine


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It is rare for me to see a patient who is not complex.

They have failed so many treatments for so many years before they call.

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This is the report of a lovely woman in her early 70’s with progressive Multiple Sclerosis for 30 years and paraplegia that has forced her to use an electric scooter the last 5 years, and power wheelchair the last 2o years. Because of total paralysis of the right lower limb, she fell and shattered her femur, the thigh bone, in August 2009. Tragically, and all too often, the surgeon failed to diagnose Complex Regional Pain Syndrome [CRPS], even failed to visit her in the hospital. CRPS increased the fatigue she had already had from Multiple Sclerosis.

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Thankfully a physical therapist suggested the diagnosis.

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Why is pain management not a required subject for physicians?

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I have written elsewhere that the American Pain Society discovered that our National Institute of Health, NIH, devotes less than half of 1% of their research dollar to pain research. Of 28 NIH institutes, none for pain, three for addiction. This will not change soon. The only hope is that RSDSA.org will succeed in collaborating with all pain organizations, groups with dystonia, chronic fatigue in order to give a voice and research dollar to advances.

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Before seeing me in September, she had 11 sympathetic blocks with no benefit.

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Does it make you wonder why 11 were done?

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How does insurance authorize 11 when 10 had no benefit? I have just learned that a doctor must indicate at least 50% relief before another will be authorized. That explains it.

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Then she was given opioids including tramadal and Butrans patch which rendered her a “zombie,” sedated, poor memory, unable to function. She tried 4 or 5 treatments of Calmare with no benefit but was advised she needed a clear neural pathway for it to work. That was not possible due to the Multiple Sclerosis.
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Lyrica caused severe edema. Gabapentin 1400 mg/day caused weight gain, increased her appetite  more than usual, but she remained on it. She craves sweets more than usual, at times uncontrollably. Perhaps it can be slowly tapered now. Advil 600 mg gave some benefit but caused ulcers that required Nexium.

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Since her initial visit a few weeks ago, she became 60% better during her two week stay.

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I will highlight only two of the new medications started.

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It may also be said that opioids are not the answer.

Opioids may perpetuate pain.
They may produce paradoxical pain or opioid induced hyperalgesia or windup.

They may block the effect of ketamine and other adjuvants that would otherwise lower pain.

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Of importance is that she was not able to tolerate clothing on her right lower limb for three years, not even a sheet, and now she is able to sleep through the night without pain for the first time in three years and able to wear a skirt. This allows her to go out with family to restaurants and even to enjoy shopping with her daughter. Her dose of ketamine is very small relative to most of my patients and she uses it only once or twice a day since most of the new medications have brought her pain down.

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At her first visit one month ago, she rated pain from 6 to 8 on a scale of 10, average 7/10. Now 60% better, ranging from zero to 7, average 4. Yes zero pain, sleeping through the night without pain and waking without pain. She had not been able to tolerate touch to the right thigh or foot and would pull her skirt above the thigh, removing her shoe.

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Now she indicates pain continues to improve.

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Of interest, despite an abundance of concern that low dose naltrexone [LDN] may flare her Multiple Sclerosis, we were easily able to increase the dose to triple what is usually called “LDN.” This did not flare her condition and may be one of the most effective medications she is taking for pain.

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What is LDN?

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The FDA has sanctioned its use in the USA only in doses of 50 to 400 mg for addiction to opioids and alcohol.

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Low dose naltrexone [LDN] is a fascinating medication. It has been used in low dose in persons with Multiple Sclerosis since 1985 when a Harvard trained neurologist in New York City, Dr. Bihari, first discovered that it relieved all disability in some patients with Multiple Sclerosis and prevented recurrent attacks. Since then, doctors in Scotland, where they have the highest incidence of Multiple Sclerosis, find that one of the earliest signs of recovery in this population is relief of neurogenic bladder. It is said that persons with Multiple Sclerosis must remain on LDN for 1.5 years before they might fully assess its value.

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 Multiple Sclerosis may be flared unless very small doses of LDN are used.

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Many with Mulitple Sclerosis cannot tolerate more than 2 or 3 mg, perhaps due to spasticity. There is a great deal of dogma on the web about its mechanism, dosing and timing for off label use. Use the search function on this site to review the prior discussions I posted on LDN, MS, CRPS.

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Naltrexone is a glial modulator.

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What’s that?!

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By serendipity, four years ago I discovered naltrexone in low dose may relieve chronic intractable pain. I had been using it for perhaps eight years in microgram doses but I found in milligram doses it is even more profound.

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The mechanism of naltrexone and a wee bit of glial research is discussed here. The Nobel Prize was awarded last year for the discovery that these glia are your innate immune system. They are profoundly important in many diseases including chronic pain, Major Depression, Multiple Sclerosis, Alzheimers, Parkinsons Disease, ALS, Autism. They produce inflammatory cytokines that lead to inflammation.

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Now that she has been home for two weeks, on a number of medications that I started, not just the ketamine and LDN, I hope she will comment on her experience and her progress since flying back to the east coast after her brief visit here.

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It is often essential to taper off opioids to allow other medication to work.

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I feel she was able to benefit from these low doses of medication because she tapered off all opioid medication prior to her visit, thus allowing her system to recover and respond to these medications. We will know more in the next few months as she slowly titrates up on some of the medications that were started.

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Next year on her return, we may be able to withdraw some of the medications depending on how well she is doing.

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Finally, ketamine does cause her to have brief side effects. Her husband likens the effect the same as half a glass of wine: “She’s really cute.” Thankfully, most people have no side effects and if they do, they rarely last more than 20 minutes.

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She sends an update below, 80 to 90% better. Hopefully this will continue to improve over the next months as she slowly increases the medication we started. And ketamine has an additive effect in some. It is anti-inflammatory.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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LDN World Database – Low Dose Naltrexone


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This is a database of persons who have tried low dose naltrexone, their diagnosis, dosage and response to it, if any. The database lists many different medical conditions.

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For example, persons with Multiple Sclerosis, will choose the link above, that has hundreds of persons with MS who have tried naltrexone. Don’t forget to see more pages once you reach the bottom. For a graph of the overall responses, then go back to the main link on Multiple Sclerosis where you see these choices:

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To view the database please click HERE

To view the Graph on how people feel about LDN please click HERE

To add your experience with LDN please click HERE – of course first select the condition you have, so your entry falls into the proper category.

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If your condition is different, just select the condition from the list on left.

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For example for fibromyalgia:

To view the database please click HERE

To view the Graph on how people feel about LDN please click HERE

To add your experience with LDN please click HERE

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Here for Irritable Bowel Syndrome, Crohn’s or Ulcerative Colitis.

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If your condition is not listed, check Other on the left side of the list.

This forum is from LDN Research Trust, a registered non-profit Charity based in the UK, with participants from many countries internationally.

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I will soon be posting several case reports of my patient responders, persons with intractable pain from various conditions. Some have been pain free one or two years on naltrexone. Some who had years of previously intractable pain have responded to low dose naltrexone and remained pain free more than one year after discontinuing LDN.

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MECHANISM

for those who like to know the science

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We have known for decades that naltrexone binds to the mu opioid receptor. It blocks the effect of opioids like morphine at the mu receptor. We now know it also acts at another receptor.

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You may wish to watch this video that explains Toll Like Receptors, TLRs for short. This is a lecture by Dr. Rachel Allen, whose PhD in immunology is from Oxford University. After that, she worked at Cambridge University on innate immune receptors such as the TLR’s.

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In 2008, it was shown that naltrexone binds at one of the Toll Like Receptors, the TLR4 receptor. There are 13 Toll Like Receptors, and so far they have studied naltrexone only at one of them, the TLR4. That is important because the TLR receptors are part of the innate immune system.

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The Toll Like Receptors are not like other receptors. Not these snug little pockets where naltrexone binds. Instead the Toll Like Receptors are like an entire football field, with enormous nooks and crannies where it has many interactions with many molecules. Now, in 2010, scientists are asking if naloxone or naltrexone is acting at TLR4 or even higher up in the cascade.

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The study of immune cell glial interactions is in its infancy. Glial cells are the immune cells in your central nervous system (brain, spinal cord). They are very involved in dysregulation of pain systems, neuroinflammation, and some neurological diseases such as Multiple Sclerosis, Alzheimer’s, Parkinson’s Disease, ALS, infections of the brain, etc.

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One of our distinguished glial scientists, Linda Watkins, PhD, in October 2010, said we are not even sure naltrexone binds to the Toll Like Receptor. Rather, it involves AKT1, close to the TLR4 receptor, very very high up in the cascade at the dimerization step, the recruitment of CD14. This is being worked out now.

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Dr. Watkins with Kennar Rice, PhD, from NIH/NIDA, et al, has a paper in press in Cell:

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Glial activation participates in the mediation of pain including neuropathic pain, due to release of neuroexcitatory, proinflammatory products. Glial activation is now known to occur in response to opioids as well. Opioid-induced glial activation opposes opioid analgesia and enhances opioid tolerance, dependence, reward and respiratory depression. Such effects can occur, not via classical opioid receptors, but rather via non-stereoselective activation of toll-like receptor 4 (TLR4), a recently recognized key glial receptor participating in neuropathic pain as well. This discovery identifies a means for separating the beneficial actions of opioids (opioid receptor mediated) from the unwanted side-effects (TLR4/glial mediated) by pharmacologically targeting TLR4. Such a drug should be a stand-alone therapeutic for treating neuropathic pain as well. Excitingly, with newly-established clinical trials of two glial modulators for treating neuropathic pain and improving the utility of opioids, translation from rats-to-humans now begins with the promise of improved clinical pain control.

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For chronic pain, targets of interest are: glial attenuation, p38 MAPK inhibition.

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Of interest, a commonly prescribed pain medication, amitriptyline, is a TLR4 inhibitor (Hutchinson, 2010).

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You can read many new publications on glia that I posted on my site here, or find it from the banner at top:

Donate to Eliminate Neuropathic Pain

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I am a member of a Neuroinflammation Research Consortium that will be studying these many conditions, some that are painful, others that are not. They involve glia and neuroinflammation.

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For more discussion of mechanisms of action of naltrexone and other publications I have posted, see here, particularly the paper by Zhang, Hong, Kim et al.

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Finally, for those who may feel they are losing heart because medicine has been too slow to adopt the use of low dose naltrexone, let me point this out:

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Dr. Linda Watkins is a University of Colorado Distinguished Professor of Psychology & Neuroscience at the University of Colorado Boulder. She is a world-renown leader in glia research and the neurological applications of glial attenuation, with a focus on alleviation of chronic pain. She is the recipient of the highest award for distinguished basic science research from the American Pain Society and the 2010 John Liebeskind Pain Management Research Award from the American Academy of Pain Management. She has over 300 peer-reviewed publications including articles in Nature, Science, Nature Neuroscience, and Journal of Neuroscience. She received over $2 million in NIH grants supporting 6 generations of IL-10 gene therapy research culminating in XT-101.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

Multiple Sclerosis & Low Dose Naltrexone – One Woman’s Story


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Vicki Finlayson and Low Dose Naltrexone

Before naltrexone relieved pain and symptoms of Multiple Sclerosis,

she had used Oxycontin and morphine for a year and a half

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While prescribing low dose naltrexone (LDN) for patients with pain in recent years, I have become deeply impressed with it. Of course, it is inescapable to get very far on the internet without seeing a flood of videos and comments on the use of low dose naltrexone for Multiple Sclerosis. I once spent an entire afternoon reading the literature and watching the videos of patients, doctors, and researchers. How I wish I had the links so I could post them here now! The stories of Dr. Pat Crowley sitting at his desk as his patients in County Kilkenny, Ireland, described the successes they had had with multiple sclerosis touched my heart deeply. Naltrexone is not a cure but its beneficial effects on the immune system have been described here and were first noted by Dr. Bihari in 1985. Dr. Crowley sees results in at least 70% of patients, particularly with neurogenic bladder.

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Vicki Finlayson has had a remarkable recovery from severe Multiple Sclerosis. I hope you will watch her interview here. It was recorded October 2008 at the Fourth Annual LDN Conference held for the first time on the West Coast at the University of Southern California, and is recounted below. Since then she has made it her mission to advocate for clinical trials of this medication but it has been difficult for patients to find doctors who will prescribe it.

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Has medicine come to the point where we no longer listen to patients, only to drug representatives that are only allowed by Congress and the FDA to discuss what has been fully approved with all its risks and benefits? Well….frankly, we are not always told all risks nor are they always discovered until years later. Naltrexone is an opiate antagonist. It will block morphine and similar pain medication. In much higher doses it has been approved for safety by the FDA in 1984 as treatment for opiate addiction, and in 1995, FDA approved for treatment of alcohol dependence. Doctors have been reserved about prescribing it off label for patients who request low doses of naltrexone for medical conditions such as Multiple Sclerosis. But the tradition of using medication “off label” for uses not approved by FDA is still alive. Weighed against the dangers of the illness relative to a small dose of a medication that appears to be benign, it appears to be a worthy endeavor to test.

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How tragic is it to hear a person with Multiple Sclerosis have to define their day in the world by how far apart the bathrooms are when needed for neurogenic bladder? That is the story that urged one Scottish research doctor to pay attention when his patient said low dose naltrexone cured his neurogenic bladder. That changed that doctor’s research career. When years of fatigue and heat intolerance may soon be gone because of this small dose, how can a doctor turn down trying it for a patient? I did a few years ago, to my everlasting regret. I know better now. In my defense back then, I had not heard any information from that patient or anyone about its favorable off label use. It was a call from another doctor. I would like to think that if the patient had made an appointment with me or written to tell me a little about it, I would have said I’d read on the subject.

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Vicki’s Story

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Vicki Finlayson had Multiple Sclerosis for 12 years and was very disabled for several of those years with Secondary Progressive Multiple Sclerosis.

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She tells how she was on Avonex for 6 years that caused flu-like symptoms so severe she was in bed for two days after each injection. She was so disabled her husband had to help her dry her hair. The medications used for Multiple Sclerosis caution about suicide risk and her husband hid knives at night for fear of what she would do to herself. She was unable to work, on medicare and social security disability. She missed the ability to work and says, “I lost so much dignity, I lost my sense of everything my parents ever taught me.”

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She detoxed herself off of opioid medication that had been prescribed for pain. Her doctors failed to help her do that. Apparently, she says, they had no experience with how to take her off those medications. And she began to take low dose naltrexone 4.5 mg. It took away all of her symptoms, including heat intolerance.

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She is delighted to be off of disability and back to work selling durable medical equipment to doctors. And she has been inspired since then to help others by raising money for research on use of low dose naltrexone for Multiple Sclerosis.

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Here is how she did it

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She walked 56 miles from her home in Auburn California to Sacramento in scorching hot 100 degree weather – without any heat intolerance that she had had for years before – to try to get the ear of the governor. She held fund raisers. And she got the attention of Dr. Bruce Cree of the UCSF Multiple Sclerosis Clinic to do the first academic trial on use of low dose naltrexone in Multiple Sclerosis, research which apparently was funded by her efforts. She is indefatigeable in her effort to help others.

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Dr. Cree’s poster presentation on the positive research outcome is here along with other scholarly publications on naltrexone. The publication can be read here: “A rapid on-line publication of the first randomised controlled trial of low dose naltrexone in MS in the Annals of Neurology has been reported prior to hard copy publication. The study randomised 80 people with MS to receive LDN or placebo in a cross-over study where people took the LDN or placebo for eight weeks, then swapped to the other study drug. This appears to be the first drug trial in MS that was not funded by the pharmaceutical industry, but by the participants themselves.”

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He closes with: “In conclusion, in this exploratory, single center study, 8 weeks of treatment LDN was associated with symptomatic benefit with respect to mental health, pain and perceived cognitive deficits in MS. Confirmation of these findings in a multicenter trial will be necessary to make definite conclusions about the possible symptomatic benefit of LDN in MS. A longer duration of treatment is necessary to determine whether LDN has any benefit with respect to physical outcome measures.”

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Here is a link to more clinical trials on low dose naltrexone, and here is a

summary of the first European LDN conference in April 2009 at Glasgow University.

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Vicki is very realistic about the chance of this work being extended by any university, NIH or the National Multiple Sclerosis Society. They rely on tens of millions of dollars to do the costly multi-center long term drug studies that must be done for this condition. That will not happen with a drug that is inexpensive, generic, and holds no promise from which any pharmaceutical company may ever hope to profit. Without such double blind studies, many, if not most doctors would be unlikely to prescribe this simple, inexpensive, low dose medication.

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Please see comments, below, that point to an excellent resource called LDNAware.org. “This website is your worldwide gateway to Low Dose Naltrexone information, resources and events.  LDN Aware is a volunteer group devoted entirely to spreading knowledge and raising public awareness about LDN as a treatment for autoimmune disease, cancer and HIV/AIDS.”

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Should LDN be used with other disease modifying drugs for Multiple Sclerosis?

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In my next post of May 16, 2010, an expert answers that question.


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“Never doubt that a small group of thoughtful committed citizens can

change the world; indeed, it’s the only thing that ever has.”


– Margaret Mead

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The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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