Memantine for Neuropathic Pain & Complex Regional Pain Syndrome, CRPS


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Neuropathic pain syndromes show an over-expression of NMDA receptors in the brain in animal models. Ketamine blocks the NMDA receptor. Another medication with the same mechanism, but in pill form is memantine. This report on six patients of the use of memantine for Complex Regional Pain Syndrome (CRPS) from 2007 in the Clinical Journal of Pain, six months after treatment with memantine, showed significant decrease in pain, improved motor symptoms and autonomic changes, and fMRI changes on the affected side improving, comparable to the unaffected side of the brain.

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It was approved for Alzheimer’s dementia gradually titrating to a dose of 28 mg/day, but for decades has been very useful off label for neuropathic pain including but not limited to CRPS, at a dose of 55 mg/day, and in recent years often prescribed for migraine.

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Ketamine is highly successful also for treatment resistant depression, and one patient, a psychiatrist disabled from the unfortunate triad of intractable neuropathic pain, migraine and treatment resistant depression, while slowly titrating to a dose of 55 mg/day, a process that takes almost 3 months, found depression relieved for the first time in decades at the dose of 35 mg. It was highly effective as one component of the multi-pronged approach for all three conditions.

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This life is a hard fact. We all need all the help, encouragement and positive attitudes we can get. Complex intractable pain and/or depression requires rational polypharmacy, selectively chosen based upon well known mechanisms, neurotransmitters, receptors, hormones, stress reduction, cognitive behavioral therapy, physical therapy, occupational therapy, nerve blocks, and spiritual understanding, etc. Several choices were summarized almost two years ago here.

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In my experience, memantine is very well tolerated with few if any side effects but covered by insurance only for mild to moderate dementia. Thus, not only is it highly challenging to treat neuropathic pain, but important to creatively meet the challenges of our backwards medical system that barely recognizes the needs of those with chronic pain.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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

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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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

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Please IGNORE THE ADS BELOW. They are not from me.

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Opioids increase risk of chronic pain – potentiate pain – faster, stronger, longer. Activate TLR4 receptor on microglia, blocked by low dose naltrexone (LDN)


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Professor Linda Watkins was the distinguished keynote speaker at the May 2015 American Pain Society annual meeting and gave the NIH 2015 Kreshover Lecture:

“Targeting Glia to Treat Chronic Pain: Moving from Concept to Clinical Trials.”

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The University of Colorado at Boulder describes her work

She has authored or co-authored over 190 book chapters, review articles and journal articles.

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Dr. Watkins’ research focuses on 3 inter-related areas. Her primary research interest is understanding how to control clinically relevant pathological pain states. Her group’s research points to a novel reason that clinical pain has been impossible to successfully control. That is, pathological pain is being created and maintained by a surprising cell type, namely glia. These cells, upon activation, dysregulate normal pain processing by the spinal cord neurons.

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Medical News Today published news of her recent study April 19, 2018

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“Opioids may increase risk of chronic pain.” They potentiate pain “faster, stronger, longer” and activate the TLR4 receptor on microglia. That receptor is blocked by low dose naltrexone (LDN).

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Opioids trigger inflammation in the brain and spinal cord. This is an elegant study by renowned Prof. Linda Watkins at the University of Colorado Boulder, with Peter Grace. His early work on LDN brought him from Australia to postdoc at her lab and now research at MD Anderson Cancer Center.

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“Having been used in one form or another for millennia, opioids beat pain into submission, quickly making the patient more comfortable. The latest study, which was carried out at the University of Colorado Boulder, turns this firmly held notion on its head.

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Senior author Prof. Linda Watkins, from the Department of Psychology and Neuroscience, says, ominously, “[…] there is another dark side of opiates that many people don’t suspect.”

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In this case, it is not addiciton issues that Prof. Watkins is referring to. Paradoxically, opioids may actually prolong pain following surgery. The results were published recently in the journal Anesthesia and Analgesia.

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Postsurgical pain and opioids examined

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For the study, Prof. Watkins and colleague Peter Grace, of MD Anderson Cancer Center in Houston, TX, carried out laparotomies on male mice. This procedure involves making an incision through the abdominal wall to access the interior of the abdomen, and it is done on tens of thousands of U.S. individuals each year.

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“Opiates are really effective for acute pain relief. There is no drug that works better. But very little research has been done to look at what it is doing in the weeks to months after it’s withdrawn.”

Peter Grace

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Following surgery, one group of rats received the equivalent of a moderate dose of morphine for the next 7 days, while another group received morphine for 8 days, and the dosage was tapered off by day 10.

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Another group was given morphine for 10 days, after which point treatment stopped abruptly. A final group was given saline injections rather than morphine as a control.

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And, in another experiment, a group of rats received a 7-day course of morphine that ended 1 week before surgery was carried out.

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Before the morphine regimes commenced, and after they had been completed, the rats’ sensitivity to touch was measured, as was the activity of genes related to inflammation in the spinal cord.

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Compared with rats given saline, those that received morphine endured postoperative pain for over 3 additional weeks. Also, the longer the morphine was provided, the longer the rats’ pain lasted.

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The study also revealed that tapering of morphine dosage makes no difference. As Grace explains, “This tells us that this is not a phenomenon related to opioid withdrawal, which we know can cause pain. Something else is going on here.”

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How can morphine raise postoperative pain?

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The next question to ask, of course, is what drives this counterintuitive effect. Prof. Watkins calls it the result of a “one-two hit” on glial cells.

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In the brain, glial cells are more numerous than neurons. They protect and support nerve cells and, as part of their role as protector, they direct the brain’s immune response, including inflammation.

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The first “hit” occurs when surgery activates glial cells’ toll-like receptor 4 (TLR4). Prof. Watkins calls these “not me, not right, not O.K.” receptors; they help to orchestrate the inflammatory response. This first hit primes them for action when the second hit occurs.

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The second hit is morphine, which also stimulates TLR4. As Prof. Watkins explains:

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“With that second hit, the primed glial cells respond faster, stronger, and longer than before, creating a much more enduring state of inflammation and sometimes local tissue damage.”

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Although the study is in an animal model and will need replicating in humans, it does line up with previous findings.

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For instance, in 2016, the same scientists published another animal study, which found that a few days of opiate treatment for peripheral nerve pain exacerbated and prolonged pain. In that study, the activation of inflammatory pathways was also implicated.

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“An unusually high number of people end up with postoperative chronic pain,” explains Prof. Watkins. In fact, millions of U.S. individualssuffer with chronic pain. “This new study lends insight into one explanation for that.”

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Interestingly, the rats that received a course of morphine that ended a week before surgery did not experience prolonged postsurgical pain, leading the study authors to conclude that there is “a critical window for morphine potentiation of pain.”

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Because opioids are currently considered the best course of action to deal with postoperative pain, if these results are replicated in humans, it leaves medical science in a difficult situation.

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This is why Prof. Watkins is focusing much of her energy on designing drugs that could be given alongside opioids to dampen down the inflammatory response. She is also exploring alternative painkillers, such as cannabinoids.”

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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

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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

~~~~~

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

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Please IGNORE THE ADS BELOW. They are not from me.

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Food Aversion – not anorexia but it’s a big problem


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I hope to post on this issue that plagues so many who have been on chemotherapy or have conditions and GI systems that profoundly limit what can be eaten.

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If you have comments that may help others, please add them. It can be the death of some people including one young boy who is 11 years old, 5 feet tall and barely 50 pounds. He has failed 5 prescription medications including marinol that I have never see effective for cancer patients and those with HIV/AIDS, including those who use marijuana.

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It’s a journey that has led to exploration of flavor and disguising foods in ways that make them less averse.

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Medical marijuana can help adults – but it (THC) is illegal to give to children, and munchies are very difficult to avoid. Weight gain is not welcome, especially if it is from pastas and sweets rather than protein, grains, veggies, fruit.

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Good choices but too limited:

Beans such as pinto beans, dal, eggs, milk, cheese, nuts, seeds, peanut butter, pork, at times shrimp, steel cut oatmeal, rice, toast.

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Skype Security Bug – Why I won’t Use Skype


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(click link, above, for article)
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Skype’s Nasty Security bug “can allow an attacker to gain system-level privileges to a vulnerable computer.” “Microsoft, which owns Skype, won’t fix the flaw”
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“ZDNet reports of a security flaw in Skype’s updater process that “can allow an attacker to gain system-level privileges to a vulnerable computer.” If the bug is exploited, it “can escalate a local unprivileged user to the full ‘system’ level rights — granting them access to every corner of the operating system. What’s worse is that Microsoft, which owns Skype, won’t fix the flaw because it would require the updater to go through “a large code revision.””
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…”From the report: Security researcher Stefan Kanthak found that the Skype update installer could be exploited with a DLL hijacking technique, which allows an attacker to trick an application into drawing malicious code instead of the correct library. An attacker can download a malicious DLL into a user-accessible temporary folder and rename it to an existing DLL that can be modified by an unprivileged user, like UXTheme.dll. The bug works because the malicious DLL is found first when the app searches for the DLL it needs. Once installed, Skype uses its own built-in updater to keep the software up to date. When that updater runs, it uses another executable file to run the update, which is vulnerable to the hijacking. The attack reads on the clunky side, but Kanthak told ZDNet in an email that the attack could be easily weaponized. He explained, providing two command line examples, how a script or malware could remotely transfer a malicious DLL into that temporary folder.””

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John Muir’s Ecstatic Experience: The Sierra. Mountains holy as Sinai.


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“Muir‘s view of the natural world is strikingly contemporary–a holistic vision of an intricately interconnected “Earth-Planet Universe.“ It is also deeply spiritual and essentially pantheistic. Muir introduces us to “plant people,“ “animal people,“ and in a passage from 1872 he muses:

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The Sierra. Mountains holy as Sinai. No mountains I know of are so alluring. None so hospitable, kindly, tenderly inspiring. It seems strange that everyone does not come at their call. They are given, like the Gospel, without money and without price. “‘Tis heaven alone that is given away.“
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Here is a calm so deep, grasses cease waving… Wonderful how completely everything in the wild nature fits into us, as if truly part and parent of us. The sunshine is not on us but in us. The rivers flow not past, but through us, thrilling, tingling, vibrating every fiber and cell of the substance of our bodies, making them glide and sing. The trees wave and the flowers bloom in our bodies as well as our souls, and every bird song, windsong, and tremendous storm song of the rocks in the heart of the mountains is our song, our very own, and sings our love.”

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Muir, John of the Mountains, Ed. Linnie Marsh Wolfe, (Boston: Houghton Mifflin, 1938) page 92.

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From Gary Snyder and Tom Killian: The High Sierra of California, page 16  
every page fills you with such beauty.
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To my patients & readers, thank you. Your words have been uplifting.


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Thank you

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If there be pain let it be


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If there be pain let it be.

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It is also part of the Self.

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The Self is poorna (perfect).

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Sri Ramana Maharshi, the great enlightened spiritual giant who at age 16 experienced the highest thereafter until almost 100 years of age. May we be blessed to awaken with these high teachings.

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Pain? Really?

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Imagine you are sitting on the banks of the Holy Ganges.

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Is pain and suffering the most amazing way to kick one into instant and serious spiritual study? Buddha must be right. We must use it, no matter what we do, as it leads to freedom of suffering. Ancient teachings give the method. So again, relax, deep breath.

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Imagine you are sitting on the banks of the Holy Ganges.

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The most holy, most revered, most powerful Mother of the Universe revered by sages for more than 6,000 years, the Mother of the Universe is flowing in front of you. Imagine. Breathe. In the Holy Presence, the body mind is not you. There is no time, space, and causation to clearly perceive you, the one Self, pure consciousness. You always were, as you are right now. Consciousness itself, clouded by misperceptions, obstructions that prevent us seeing the awakened being we are.

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Ramana Maharshi taught the simplest, most direct method. No need for religion, or you may choose the path of religion, but all paths lead to the Absolute. All rivers lead to the ocean.

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If there be pain let it be.

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It is also part of the Self.

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The Self is poorna (perfect).

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We are not the body, not the mind.

We are the Self. The Infinite.

Always have been.

 

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The material on this site is for informational purposes only.

.

It is not legal for me to provide medical advice without an examination.

.

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

~~

Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

~~~~~

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

.

Please IGNORE THE ADS BELOW. They are not from me.

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