Complex Regional Pain Syndrome in Remission 6 years


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 Complex Regional Pain Syndrome

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Celebrating six years of complete remission

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Why ketamine should never be used alone

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I first posted her case here. 

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For years, pain below both knees was 8 to 9 on scale of 10, “like I had swallowed a fire burning.”

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She was unable to stand or walk for more than 4 years before seeing me. This week, I again saw this very healthy athletic RN who at almost 70 of age is very youthful, very energetic. She failed IV ketamine given first by Dr. Schwartzman daily for one week, then boosters for 8 months.

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After 8 months of ketamine, then no response at all. None. 

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That’s when I prescribed other glial modulators and rational polypharmacy that brought CRPS into remission. Then very very slowly tapered off all but one, leaving only low dose naltrexone (LDN) for the last 8 years. Zero pain. None. Hiking, working, fully active.

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When used in conditions with known neuro-inflammation, rats or human, LDN is a one of the most powerful, most effective glial modulators I have ever seen clinically in my patients in the last 15 years.

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Until proven otherwise clinically, LDN should be taken lifelong in those cases.

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This website is not for email.

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The advertising is not approved by me and

unrelated to anything on these pages.

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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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Protein critical for neuromuscular junction modulates glutamate


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Protein critical for neuromuscular junction

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Lrp4 in astrocytes modulates glutamatergic transmission

Published online June 13 2016

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“We found that glutamate release in the brain was impaired in mice lacking low-density lipoprotein receptor–related protein 4 (Lrp4), a protein that is critical for neuromuscular junction formation.”

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Could this relate to POTS which improves with mestinon? or chronic fatigue of so many conditions (CRPS, fibromyalgia, Lyme Disease)?

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As reported in Neuroscience News

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“In the neuromuscular juncture, Mei’s lab found several years back that LRP4 on the muscle cell surface is a receptor for agrin, a protein that motor neurons release to direct construction of the nerve-muscle juncture. His lab later identified antibodies to LRP4 and agrin as new causes of myasthenia gravis. The new research indicates that release of ATP by astrocytes is also regulated by agrin signaling.”

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…”When you take LRP4 out of astrocytes, ATP levels released by those astrocytes go super high, which suppresses glutamate transmission,” Mei said.

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“Now it’s clear that glial cells, like astrocytes, have a role in neurodevelopment and longer-term in regulating communication between two neurons.”

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Original Research from the Medical College of Georgia: by Xiang-Dong Sun, Lei Li, Fang Liu, Zhi-Hui Huang, Jonathan C Bean, Hui-Feng Jiao, Arnab Barik, Seon-Myung Kim, Haitao Wu, Chengyong Shen, Yun Tian, Thiri W Lin, Ryan Bates, Anupama Sathyamurthy, Yong-Jun Chen, Dong-Min Yin, Lei Xiong, Hui-Ping Lin, Jin-Xia Hu, Bao-Ming Li, Tian-Ming Gao, Wen-Cheng Xiong and Lin Mei in Nature Neuroscience

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This website is not for email.

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The advertising is not recommended by me

and is not related to anything on these pages.

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All patients: sign up for RSS feed top right


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Change happens rapidly in medicine. Long distance patients are especially affected. I can not continue to return 60 telephone calls each day about changes outside of everyone’s control. Doctors are subject to sudden conferences required by regulatory agencies. Vacation, and emergencies do happen — wildfires, earthquakes, loss of cell phone towers, electric lines down.

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If you are my patient, have you signed up for RSS on this website? If not, sign up now for RSS, at top right.

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Your safety is the most important concern. Preventing unexpected cost is another. Devastating as is your intractable pain or your PTSD or treatment resistant depression, we all need to be updated as soon as change occurs. Plan ahead, be prepared, and hope for smooth conditions.

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After you sign up for RSS and after you have read about PJ’s closing, only after that, if you still have questions, then please email or text me – be sure to include your name.

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This website is not for email.

My patients all have my email.

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Patients may be very disappointed and upset if some need to stay in San Diego 2 or 3 days longer waiting for medication refills. Please understand, I will work with one and only one compounding pharmacy — I have seen too many failures and unsafe methods, but I do need you to stay updated on more than one issue.

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I have no easy way to rapidly relay important information to so many of you. This website is not for email.

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Patients may be angry or very unhappy due to change and expectations that the new pharmacy is the same as the old. This is one example of many frustrations with the American medical system.

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If any other questions and if you live a distance, please email or text me – be sure to include your name if you text, so I can identify who you are.  

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This website is not for email.

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Advertising of products on this free website

is not my recommendation.

Please ignore advertising.

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Ketamine Prescribed Since 1994 – My Experience


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Ketamine offers an opportunity for normal life unmatched by any medication I know of when given off-label for chronic treatment of intractable pain, treatment resistant depression, bipolar depression, juvenile bipolar disorder. It is one of the safest medications I have prescribed in 41 years of medicine. I have never seen anything more effective – it is not a cure, but remission is highly possible. Please refer to peer reviewed references since 2009 on this website on ketamine and depression or pain. Read elsewhere about street drugs, junkies, addicts and media headlines.

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Never Ketamine Alone

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Ketamine is short acting no matter how it is given.

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I never prescribe ketamine by itself – a fools errand; the religion of ketamine is like the religion of opioids. Decades of intractable conditions and chronic neuroinflammation require more than one short acting drug and usually require a multi-disciplinary approach. I work with psychologists or psychiatrists and other specialists when indicated.

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Entourage effect 

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DRUGS ARE LIKE POLITICIANS. A FAMOUS POLITICIAN MAY WALK UNRECOGNIZED, BUT WHEN YOU SURROUND HIM OR HER
WITH MANY PEOPLE, EVEN OF LESSER STATUS, THE POLITICIAN HAS A FAR MORE POWERFUL EFFECT.

Mechoulam

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1994 – I first prescribed IV when teaching cancer pain at MD Anderson Cancer Center.

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2001 – prescribed for outpatient care of chronic intractable pain

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2011 – prescribed for treatment resistant depression, bipolar depressed, juvenile bipolar/fear of harm phenotype often diagnosed as oppositional defiant disorder.

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2009 – writing about ketamine, neuro-inflammation and glial modulators on this site, with classic references to publications from the foremost peer reviewed journals, including low dose naltrexone, oxytocin.

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Dosing

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Depression, Bipolar Disorder, Juvenile Bipolar/FOH, treatment resistant – may need a dose only twice daily or every 3 days. The dose and frequency of use cannot be predicted – it is idiosyncratic – look up that word.

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Intractable pain – dosing and frequency of medications is very different than for depression.

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My work with these medications, these glial modulators, is too extensive to annotate on these pages. This website since April 2009 has references for context and guidance with active links to peer reviewed publications. Example:

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Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype. D Papolos et al, J Affect Disord. 2013 May;147(1-3):431-6.

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RESULTS:

Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated.

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CONCLUSIONS:

Intranasal ketamine administration in treatment-resistant youth with BD-FOH produced marked improvement in all symptomatic dimensions. A rapid, substantial therapeutic response, with only minimal side effects was observed. Formal clinical trials to assess safety and efficacy are warranted.

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mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists. R Duman et al, August 2010, Science, Science 2010 Aug: Vol. 329, Issue 5994, pp. 959- 964. [this article free with registration]
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ABSTRACT:

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We observed that ketamine rapidly activated the mammalian target of rapamycin (mTOR) pathway, leading to increased synaptic signaling proteins and increased number and function of new spine synapses in the prefrontal cortex of rats. Moreover, blockade of mTOR signaling completely blocked ketamine induction of synaptogenesis and behavioral responses in models of depression. Our results demonstrate that these effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and could contribute to the fast antidepressant actions of ketamine.

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“The resulting protein synthesis and neuronal alterations in the medial prefrontal cortex are the opposite of those produced by chronic stress….”

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Read elsewhere about street drugs, junkies, addicts and media headlines.

If that is you, see an addictionologist, not me.

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Some medications can be drugs of abuse but every patient and every medication that I dispense is followed meticulously. If any sign of misuse or abuse, that unfortunate person is immediately discharged and referred elsewhere.

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For my Home Page, click here: 

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Welcome to my Weblog on Pain Management!

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This site is not for email or medical advice.

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It is not legal for me to give medical advice

unless you are my patient which means I have done a medical history and examination.

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I generally accept only those who have failed most or all known treatments, and only those who I feel I can help.

 

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I interview each patient before accepting.

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Any advertising below is not recommended or condoned by me.

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Pain. Exciting Renaissance for Sodium Channels, 9 of them


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Exciting Pain Discoveries at UCSF with

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Tarantula Toxins

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UCSF group of 20, including Allen Basbaum,

published yesterday in Nature:

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Selective spider toxins reveal a role for

the Nav1.1 channel in mechanical pain

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I’ve condensed the article by Chelsea Leu in Wired

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UCSF’s David “Julius is a physiologist studying pain, and the toxins in … venoms make you hurt in different ways. By looking at how and where those toxins attack different parts of the nervous system, Julius and his lab might find some that could be used to develop better painkillers.”

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There are many ways to feel pain:

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Thermal – when you burn yourself w ice, eat a hot pepper

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Chemical – “when lactic acid builds in your legs during a run or your cells get damaged.”
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Mechanical – “pain of having a giant, bristling tarantula sink it’s fangs into your hand”

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“And then there’s the big slug of venom that spider delivers straight to your nervous system, a searingly painful combination of any of the three prior types.”

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…”Basically, they are finding new ways to inflict pain,” says Chris Ahearn a biophysicist at the University of Iowa.”

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“Now, Julius and his coauthors have published the latest results of their search in today’s Nature. They isolated two kinds of toxins from the venom of a tarantula called Heteroscodra maculata, and discovered it causes mechanical pain. That’s what you feel when your body gets pinched or strained or prodded, and it also underlies chronic pain in afflictions like irritable bowel syndrome. When the scientists injected mice’s paws with small doses of the toxin, they became much more sensitive to getting poked.”

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…sodium channels…..

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…”tarantula venom, though, has two toxins that target a very specific type of sodium channel. And once scientists figured that out, they deduced that those sodium channels control mechanical pain.”

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That link could be key to developing new painkillers. Scientists had sort of overlooked sodium channels before, says Ahern, ignoring the nuances between the types—each is big and complex, and the nine types of channel aren’t all that structurally different. But those nuances turn out to be very important.

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“It’s kind of a Renaissance for sodium channels,” *********Ahern says. And drug companies would love to target specific sodium channels to get at some types of pain and not others.

Case in point: The local anesthetics doctors use now, like lidocaine, block all sodium channels. That shuts down all nerve communication in an area for a short period of time. Which is fine if you’re getting a root canal, but not so great for recurring ailments like back pain. “The pharmacology of pain is still pretty primitive,” Julius says. And the medicines that treat chronic pain—opiates, mostly—aren’t too swell either. “Opiates are embarrassingly blunt,” says Jeremiah Osteen, a post-doc in Julius’ lab who led the Nature study. “They don’t do anything to the pain signal itself, they just dampen the body’s response to it.

 

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[Interrupting this to say: Exactly.

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“opioids do nothing to the pain signal itself” as opposed to glial modulators that help to restore balance within the innate immune system.

Pardon our ignorance. Now begs questions:

1. Please remind us what triggers each type sodium channel.

2. Glial modulators help to”reset” the sodium channels. Is that correct?

3. Do sodium channels and glia interact? How?

 Any hints would be lovingly appreciated.]

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Cont’d

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“So, more knowledge of what controls different types of pain could mean better pain meds. And those channels might be helpful in targeting other, non-pain conditions. For instance, the sodium channels targeted by the Heteroscodra maculata‘s toxins hadn’t really been studied before in the context of pain, but scientists had previously discovered that mutations on that channel often cause epilepsy. Julius and his team suggest the toxins they found could be fruitful starting points for epilepsy researchers to develop drugs. [of dual use drugs epilepsy and pain.]

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In pursuit of pain

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Julius’s lab didn’t pull those tarantula toxins out of a hat. With hundreds of venoms in their library to sort through, they’ve developed a systematic, laborious process to home in on the interesting ones. “We’re screening pretty much continuously,” Osteen says. They test every new venom they get by applying each to mice and rat nerve cells in a dish. If a subset of the cells lights up—showing up neon blue against a purple background, thanks to a calcium dye—it’s a sign that the venom is targeting some pain receptors and not others.

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Of the venoms they test, about 15% turn up promising. From there, it’s a matter of winnowing out the toxins they find interesting. The trickiest parts, Osteen says, are figuring out what exactly each toxin is and where exactly it’s targeting. The lab separates out the promising venoms into their individual toxins, in almost imperceptibly tiny droplets. (“They’re very potent,” Osteen says.) To determine what’s what, they use mass spectrometry, sequence proteins, analyze genes in the animals’ venom sacs, and synthesize the toxins. Sometimes, they call in specimens of the venomous animals themselves to collect RNA (molecules that show which genes are being expressed and when). Then, the scientists throw out the toxins that have been studied extensively, and delve into the rest.

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The lab isn’t stopping at a couple of toxins that may be medically promising, however. Julius and his colleagues are intent on figuring out how the entirety of pain works, doing what Osteen calls “curiosity-based science.” Of course, they’ll look closely at any serendipitous medical discoveries that might branch from their research, but they’re mostly researching this stuff because, well, it’s cool. Why wouldn’tyou want to learn all about venom?

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Still, their work is eminently practical. Pain is universal, Julius points out, and it’s something everyone is viscerally interested in. “On a fundamental level,” he says, “it shapes how we experience the world.” Though the experience of a debilitating tarantula bite might be one you’d want to stay a world away from.

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 For my Home Page, click here: 

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Welcome to my Weblog on Pain Management!

 

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This site is not for email or medical advice.

.

It is not legal for me to give medical advice

unless you are my patient

which means I have done a medical history and examination.

.

I generally accept only those

who have failed most or all known treatments,

and only those who I feel I can help.

 

.

I interview each patient before accepting.

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******************

Any advertising below is not recommended or condoned by me.

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