Soothamide (PEA) Cream Helps Psoriasis & Seborrheic Dermatitis


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I have posted on PEA (palmitoylethanolamide) for several years on this site – use the search function top left above photo and type in PEA. No prescription is needed. Before it was available in the US, patients ordered it from the Netherlands where it is sold as PeaPure. One whose neuropathic pain was finally relieved by it, ran out, flew to the Netherlands just to pick up an emergency supply and flew back immediately. Thankfully Vitalitus began offering PEA capsules in the US a few years ago, and then made the 2% cream called Soothamide, which I have also posted on this site. It may even relieve the neuropathic pain of Complex Regional Pain  Syndrome (CRPS).

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Palmitoylethanolamide (PEA, or PeaPure in Netherlands) is nontoxic, anti-inflammatory, analgesic, and has no side effects. Your body makes it; plants make it. Years ago the publications on it were extensive. A Nobel Prize winner published on it in the early 90’s. When taken in capsule form for CRPS, I have seen it take 6 or 8 weeks to be effective, but when it relieved pain, it lowered pain from very severe to mild in a patient bedridden for 6 years. I have seen the cream relieve neuropathic pain instantly in a couple minutes in some with CRPS. I have seen the cream fail to relieve CRPS pain in one patient, who then wiped the remainder of the cream along the lumbar spine of her dad who had been groaning with pain, who had instant relief. And I have published on its use for vulvodynia, discussing its autocoid mechanism.

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Skin conditions can be their own constant day and night torment. A patient reports almost complete immediate relief from the itch of psoriasis and seborrhea (around eyes and all over scalp). Itch can be a form of neuropathic pain besides more common causes such as allergy. The rash, the bleeding crusted itchy skin of those two conditions is treated by prescription steroid creams that can thin the skin, and thin skin itself can predispose to bleeding, further discomfort, and frankly did not help this patient. If you use steroid creams, it must be applied 3 or 4 times a day and use gloves or caution where you rub your fingers — risk thinning the delicate skin near eyes and nether regions as weeks and weeks drag on. Soothamide worked quickly, not needing 3 or 4 applications per day.

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Instantly the itch was markedly better. And overnight! the rash was markedly improved. The patient had had some mild relief from the bleeding itchy scabs on scalp with T/Sal shampoo but not great, for weeks and weeks. Before that, DHS Zinc shampoo helped only mild “dandruff”, did not touch the crusts and itch. Aloe Vera helped the itch for a few hours. Steroid creams were no help for itch, for 4 months scratching the delicate skin around eyes with hard scratchy cloth almost like a dry loofah sponge. Soothamide 2% took away the itch around eyes immediately though it can easily get into eyes when washed or when rubbing the eyes, it does not burn. It is truly very soothing.

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It’s also a remarkable moisturizer, absorbs very quickly, is not greasy, and for those whose other skin conditions are unusually thickened, it would likely be worth a try.

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I see Vitalitus now also sells CBD, that is cannabidiol, the cannabinoid from the marijuana plant that has no psychotomimetic properties – does not make you “high”. GW Pharmaceuticals’s “Epidiolex”, their CBD, recently received FDA approved for epilepsy. Imagine! a Schedule I drug received FDA approval! hmmm, must not be deadly after all. Wait til the DEA kills that idea. Does congress make sense when they dictate medicine?

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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 Kill White Americans – Is it opioids or suicide or addiction or untreated pain?


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Drug Overdoses Propel Rise in

Mortality Rates of Young Whites

New York Times

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Yes, white Americans, headlined yesterday by Gina Kolata and Sarah Cohen, New York Times science writers.  This article points to the highest mortality in young whites. See post early November on the Princeton researchers who reported deaths in white Americans. True, infants and children have severe pain, but this new article is on young white adults.


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Those who are anti-opioid and those who lost a loved one from opioids and heroin (an opioid that helps pain), will send in comments to the paper so that everyone can see how bad opioids are. Most patients who take opioids are too disabled from pain to write.

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Pain is stigmatized, opioids stigmatized, people in pain are stigmatized, doctors who treat pain are stigmatized. Any wonder 97% of medical schools do not teach pain management?

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Is it opioids or suicide or addiction or untreated pain that is killing our youth?

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How many suicides have opioids prevented? Americans make up less than 5% of the global population but consume 80% of the world’s supply of opioid prescription pills. What if your cancer pain now becomes severe intractable chronic pain? Cancer has been changing. The survival rate has increased, and many of these cancer patients treated with opioid therapy, survived the cancer but have residual chronic pain from cancer or its treatment. Surely they are among the 18,000 white people who died.

 

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Please read the earlier post this week on the ethics of opioid treatment, on

CDC’s imminent radical cut in opioid doses for 100 million patients nationwide.

Use search function above photo – type in CDC or DEA.

Your pain. Your lives. Their profit.

A thorny problem.

Tell us what happened to you. Doctors, tell us what you are seeing.

Have you been denied disability due to pain? Denied non-opioid treatment?

Chronic severe pain affects forty million Americans.

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KONICA MINOLTA DIGITAL CAMERA

Some insurers have denied or limited non-opioid treatments yet continued expensive opioids for decades. Has your insurance refused your treatment? Pain specialists have been barraged by denials for years.  Please comment below.

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As noted last week, I have spent 15 years developing alternatives to failed opioid treatment for chronic intractable pain and writing about that on these pages since April 2009. But opioids must be available as last resort.

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FACT:

  • Opioids killed almost 18,000 Americans in 2014 – prescription opioids, not street drugs.

  • 40 million American millions with severe pain, millions not thousands

  • 100 million with chronic pain.

  • CDC will imminently, radically cut everyone’s opioid dose

  • Health insurers will oblige, and incidentally show increased profit to shareholders

  • Suicide increases with untreated pain

  • Death rates for “whites ages 25 to 34 was five times its level in 1999”

  • This age group has more injuries from work and play that can lead to disability, job loss

  • Insurance is unaffordable or not purchased by many young adults

  • My own colleagues cannot afford high deductibles – prescriptions are now counted in deductibles, now unaffordable

  • Can you afford $20,000 per month for your opioid or is cheap heroin more affordable? Can you afford your usual drugs on Medicare once you are in the “donut hole.” Can you afford $28 per day, $840 per month for gout, when colchicine was 12 cents a day a couple years ago?

    • Do insurance denials increase liklihood of cheaper alternatives such as heroin or illegal marijuana resulting in death by drug dealer?

    • Do exhorbitant costs of opioids lead insurers to deny your medication?

  • Insurers have refused to pay for abuse-deterrent and tamper-resistant formulations of opioids

  •  Insurers have refused to pay for proven, widely accepted, nonopioid analgesics:

    • Lyrica

    • Horizant

    • Gralise

    • Cymbalta

    • Does it help the DEA and NIH and universities to teach those as nonopioid alternatives when they are not covered and not affordable the rest of your life?

    • Insurers deny every known compounded analgesic though low cost and effective, even for Tricare’s disabled veterans, even 5% lidocaine ointment for nerve pain, dextromethorphan, oxytocin, low dose naltrexone – Stanford published research on naltrexone years ago and now doing research on it again for CRPS, many many others

    • Insurers deny proven analgesics that are used by armed forces, university hospitals, select doctors, for life threatening pain: ketamine

    • Insurers deny off-label analgesics that may work better than opioids, e.g. memantine, an Alzheimers drug – can relieve intractable nerve pain (French publication on CRPS/RSD pain)

    • Insurers deny medications that reduce side effects of opioids, e.g. nonaddicting modafinil popular with students, to increase alertness when opioids cause drowsiness that may cause injury, death – gosh 10 years ago!

    • Is drowsiness the cause of some of those 18,000 opioid deaths?

  • Health insurers have refused coverage for treatments such as P.T., psychotherapy for coping skills, blocks.

  • Insurers deny medications that relieve the withering side effects of opioid withdrawal, making it impossible for many to taper off, e.g. Adderall, Wellbutrin (dopamine)

  • Cannabis, a nonopioid, classified by US Congress as Schedule I, illegal federally for human use, illegal to take on a plane or cross state/national borders, found on meteorites, made by sponges and some of the earliest living species on the planet, used for thousands of years for pain, while cocaine and methamphetamine are classified as Schedule II for prescription purposes.

  • Opioids, even vicodin, require monthly doctor visits, costs, monthly for sixty years

  • Why whites dying of opioids? People of color are denied prescription opioids. Stark data published for decades.

  • Heroin is an opioid, cheap and available; its “unAmerican” – used in England for pain, used thousands of years for pain

  • Untreated pain is one reason people turn to heroin, affordable is another

  • Violence and drinking and taking drugs can begin with chronic pain and job loss, not always the other way around, chicken egg

  • Opioids cost pennies to make, patient’s cost is $20,000 per month for Rx. Insurers paid what the market would bear… in the old days. Who is trapped in the middle of this fight for shareholder profit?

    • How many of us would take 2 or 4 extra pain pills when pain spikes to extreme for days?

    • If you are disabled, can you afford insurance or expensive prescription drugs?

  • “Poverty and stress, for example, are risk factors for misuse of prescription narcotics,” Dr. Hayward said.

  • When you are not getting enough sleep and rest, working too many hours overtime or 3 jobs, inflammation and pain spikes

  • Misuse of opioids in > 33% (perhaps 48%?) of cancer patients at Memorial Sloan Kettering Cancer Center in high resource settings when insurance was better, published 1990’s.

  • Cancer pain – usually time limited. Intractable chronic pain – forever.
    .How many jobs will be lost and how many suicides when CDC imminently imposes strict cuts in opioids?

  •  DEA recently requires every pain patient taking opioids, including those with cancer, to be diagnosed “Opioid Dependent” — not only addicts – the same diagnosis for pain patients includes addicts. The term “addiction” has been equated to dependence by most psychiatrist over the past 30 years. It may be interesting to see what criteria are used to define “addiction” if any, in DSM V. Some important members acknowledge that the addition of dependence into addiction in DSM-III was a mistake….the DSM-V criteria will get rid of “abuse”, and will include craving. it will also apparently eliminate the legal/criminal criteria. DSM comments are extracted from here, with many good arguments on this epidemic, such as: “The US is leading the way in eradicating pain, but in doing so has created an unwanted byproduct: painkiller addiction.”
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    What would you want if you had intense chronic pain?

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    “For too many, and especially for too many women,” she said, “they are not in stable relationships, they don’t have jobs, they have children they can’t feed and clothe, and they have no support network.”

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    “It’s not medical care, it’s life,” she said. “There are people whose lives are so hard they break.”

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Opioids kill – or is it untreated pain?

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Pain kills, a maleficent force.

No one can help you. Only you have the tools to do it

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Alarms went off for me on radical opioid cuts in October and I posted when

DEA suddenly held conferences across the nation on sharply cutting opioid doses.

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How many of us especially seniors and male persons refuse to learn or use coping skills that

reduce pain without medication?

How many of us refuse to diet and lose weight to reduce pain and/or disability?

Politicians are sued if they tax sales of sugar loaded soft drinks.

One single can of soda per day exceeds acceptable sugar limits for entire day.

Snacks need to say much much time it takes to burn off fat –

quarter of large pizza 449 calories, walk off 1 hr 23 min;

large coke 140 calories, walk off 30 minutes.

Foods can be anti-inflammatory or pro-inflammatory.

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Obesity is pro-inflammatory.

So is lack of sleep.

People who sleep with animals in their bed and their bedroom, I’m talking to you.

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Yes, pain is in your mind.

Chronic back pain is no longer in the back, it’s in the brain, the pain matrix.

It’s behavior, not just pills. Pain is an emotional and psychosocial  and spiritual experience.

Work on it! Constantly.

Lord forbid we should teach stress reduction and meditation in grade school

and improve school lunches before kids start looking for heroin for pain.

Yes, kids have chronic pain, are sleep deprived, often obese.

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Isn’t this all un-American?

Injuries, pain, habits, pace activities, learn to avoid and treat pain – start young.

Taxpayers end up paying for ignorance and disability.

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I will soon be posting published research that documents health insurers have refused to pay for nonopioid treatment and how health care policy aimed at all people with chronic pain leads to suicide when drastic cuts are made to opioid doses – Washington State we are looking at you. Florida you’ve made headlines and 60 Minutes TV specials years ago.

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Do please comment below if your health insurer has refused medication, physical therapy, psycho-therapy, cognitive behavioral therapy, stress reduction, for chronic pain.

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How many of you have been denied social security disability by doctors who don’t know how to diagnose RSD, Complex Regional Pain Syndrome? Let me know. I will pass on that data to researchers collecting information on untreated pain.

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I have written many times on these pages, and more often than ever these past years as insurers cut back more and more. This will rapidly get worse. We need your data.

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Please send in your stories. You are not alone.

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So many issues. Steven Passik, PhD, was interview by Lynn Webster, MD – emphasis in bold is mine. Dr. Passik pioneered in management of chronic pain and pain in addicts. He has read some of Dr. Webster’s book. “You’re calling, the need for love and connection and all those things in the book, I’ve been – what’s largely lacking is outright, at times animosity towards people with pain and I think there’s a lot of projections sometimes because the therapy – the stigmatized disease – treated in stigmatized people with stigmatized drugs and interventions and so, it’s like a hat trick of stigma.  I’ve been to my share of pain conferences lately that people are really talking about, “Okay, well there’s come a realization that opioid-only, drug-only therapy, is really not going to work to the best majority of this population.  It doesn’t [mean] that opioids should be ignored and we’ll get into that later, but that they’re going to work in isolation and should never been expected to.  And then they start advocating things that are a lot like supportive and cognitive behavioral therapy and to be practiced basically by the primary care physician or the pain doctor.  And the idea that, to me that’s in a way comical because as a psychologist myself, we’re dealing with the system wherein cognitive behavioral therapists can’t even get paid to do cognitive behavioral therapy.  And so, I think something’s got to give, and I think one of the main obstacle is that – and this really gets into the next question as well but I’ll come back to that more specifically – but when people have a set of whatever chronic condition that involves psychiatric motivational, lifestyle, spiritual as well as nociceptive elements, and we put a premium only on what you do to people, prescribed to people, put in people, take out of people, and then that’s only going to relegate the other kinds of treatment or the other kinds of ways in which a caring physician and treatment team would spend time with the patient to the very poorly reimbursed category.  You’ll always going to have a problem with people being treated with the kind of respect that should go along with treating that kind of an illness and it’s not unique even to chronic pain.  I’ve seen treatment scenarios with people who are taking care of people with pancreatic cancer, have an afternoon clinic that has 45 people in it.  I mean how you – something’s got to give in our healthcare systems and I do think that patients are going to have to stand up and say, “I don’t want to be on a conveyor belt.  I want to spend some time and make a connection with the people that are taking care of me and it’s not just about the piece paper in my hands, for a prescription or that I walk out the door with.”

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Clematis Blue.

 The New York Times article further says:

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…This is the smallest proportional and absolute gap in mortality between blacks and whites at these ages for more than a century,” Dr. Skinner said. If the past decade’s trends continue, even without any further progress in AIDS mortality, rates for blacks and whites will be equal in nine years, he said….

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…Not many young people die of any cause. In 2014, there were about 29,000 deaths out of a population of about 25 million whites in the 25-to-34 age group. That number had steadily increased since 2004, rising by about 5,500 — about 24 percent — while the population of the group as a whole rose only 5 percent. In 2004, there were 2,888 deaths from overdoses in that group; in 2014, the number totaled 7,558….

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…For young non-Hispanic whites, the death rate from accidental poisoning — which is mostly drug overdoses — rose to 30 per 100,000 from six over the years 1999 to 2014, and the suicide rate rose to 19.5 per 100,000 from 15, the Times analysis found….

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…For non-Hispanic whites ages 35 to 44, the accidental poisoning rate rose to 29.9 from 9.6 in that period. And for non-Hispanic whites ages 45 to 54 — the group studied by Dr. Case and Dr. Deaton — the poisoning rate rose to 29.9 per 100,000 from 6.7 and the suicide rate rose to 26 per 100,000 from 16, the Times analysis found….

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…Eileen Crimmins, a professor of gerontology at the University of Southern California, said the causes of death in these younger people were largely social — “violence and drinking and taking drugs.” Her research shows that social problems are concentrated in the lower education group.

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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.

Relevant comments are welcome.

If any questions, please call the office to schedule an appointment.

This site is not email for personal questions.

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

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Please be aware any advertising on this free website is

NOT advocated by me and NOT approved by me.

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Severe pain in nearly 40 million adults, 17.6 % – NIH budget **less** than 0.5% for pain research in 2008


 

 

 

 

In 2008, the President of the American Pain Society wrote:

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“Based on an APS sponsored survey (Bradshaw et al., 2008), extramural support for pain research has declined to less than 0.5% of the NIH budget.

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Less than half of 1% . . . .

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17.5% of people with severe chronic pain deserve better.

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Information released August 11, 2015:

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A new analysis of data from the 2012 National Health Interview Survey (NHIS) has found that most American adults have experienced some level of pain, from brief to more lasting (chronic) pain, and from relatively minor to more severe pain. The analysis helps to unravel the complexities of a Nation in pain. It found that an estimated 25.3 million adults (11.2 percent) experience chronic pain—that is, they had pain every day for the preceding 3 months. Nearly 40 million adults (17.6 percent) experience severe levels of pain. Those with severe pain are also likely to have worse health status. The analysis was funded by the National Institutes of Health’s National Center for Complementary and Integrative Health (NCCIH) and was published in The Journal of Pain.

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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.

Relevant comments are welcome.

If any questions, please schedule an appointment with my office.

This site is not for email.

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

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Be the change you wish to see – or walk away. Money at NIH


 

 

A Turning Point

 

$$$$$ MONEY $$$$$

 

at NIH

 

May not come this way again

 

NIH developing

5-year NIH-wide Strategic Plan

 

 

 

Donate to organizations, below

They can provide feedback to NIH via the

RFI Submission site


 

 

 

John C. Liebeskind, 1935 – 1997, distinguished scholar and researcher, past president of the American Pain Society, had the radical idea that pain can affect your health.

 

Research decades ago by an Israeli team at UCLA and others had shown “that pain can accelerate the growth of tumors and increase mortality after tumor challenge.” Decades ago Professor Liebeskind lectured all over the country: Pain kills.

 

He wrote an editorial in 1991, summarizing a life’s work:

 

“Pain and stress can inhibit immune function.”

 

 

Quoting John Bonica, the father of modern pain management, he wrote:

 

“Bonica has long argued that the term ‘chronic benign pain’ (used in distinction to pain associated with cancer) is seriously misleading.  Chronic pain is never benign, he contends; “it is a ‘malefic force’ that can devastate its victims’ lives and even lead to suicide.”

 

 

Liebeskind continues, “It appears that the dictum ‘pain does not kill,’ sometimes invoked to justify ignoring pain complaints, may be dangerously wrong.”

 

Pain mediates immune function

 

Importantly

 

  Opioids mediate the suppressive effect of stress on natural killer cells,

 

 published in 1984, immune system.

 

Alcohol increases tumor progression, 1992, immune system.

 

It used to be news.

He did not live to see change.

 

People just want to go on doing what they’re doing.

They want business as usual.

 

 

After 1991, we saw the great discoveries of neuroinflammation, pioneered by Linda Watkins, PhD, the early understanding of the innate immune system, its involvement in chronic pain and depression, and a few weeks ago, a British team showed neuroinflammation in teens with early signs of schizophrenia and DNA markers.

 

 

Major Depression has the same neuro-inflammation found in chronic pain, often responding to same medications, in particular glial modulators – immune modulators. Now, perhaps early schizophrenia will respond to glial modulators, reducing inflammation seen on scan in teens, before they become homeless and burned out by antipsychotic drugs

 

Inflammation out of control destroys neurons

 

Fire on the brain

 

 

We must be the change we wish to see

 

It’s not just the Bern. It’s been starting. Forces are finally coming together. We want change. It’s been too much. Too long.

 

We won’t take it anymore.

 

I figure if I tell you about it, you might just mention it to someone to pass it on. That is all. One small action may lead to change. Activate inputs to the NIH strategic plan.

 

 

~ Action needed ~

 

Prices of drugs becoming unaffordable

No new drugs for pain or major depression

Research to repurpose existing drugs

Expose the politics destroying our compounding pharmacies

 

Above all

The #1

Major Priority:

Request NIH to solicit priority call for research on

Glial modulators of the

Innate immune system

 

 

Why?

 

Glia modulate

chronic pain, major depression

and almost every known disease

 

Glia are your innate immune system

 

Inflammation kills

 

 

 

 Stress kills. Inflammation kills.

 

 

Pain kills

 

In the 1970’s, Professor Liebeskind and an Israeli team at UCLA injected cancer cells to two groups of rats that had sham surgery. Cancer spread much faster and killed far sooner in the group with poor treatment of surgical pain.

 

 

~ Pain kills ~

 

He lectured all over the country

 

Forty five years ago

 

 

I’m gonna be dead before I see this country do anything but unaffordable opioids and the magical ineffective trio of gabapentin, Lyrica, Cymbalta to treat chronic pain. The devastating, blind, nationwide emphasis does nothing to address the cause: inflammation, the innate immune system gone wild.


 

 

Innate immune system in action

 

Untreated pain suppresses the hormone systems too.

 

Untreated depression – same inflammation kills lives.

 

Where’s the money?

 

We are the change we wish to see. It’s pitiful I am so lazy. Suddenly, too late, we may need something, but, aha, no new drugs in the pipeline.

 

 

 

~ Make a joyful cry to NIH ~

 

They are soliciting input from professional societies

 

If your condition has failed all known drugs for pain or major depression, then make a joyful cry to NIH, now, before they give away all that nice new $$$$$money$$$$$.

 

 

Follow and join

 

American Pain Society

 

 

International Association for Pain

celebrating 40 years of pain research

 

 

Reflex Sympathetic Dystrophy Syndrome Association

help for CRPS/RSD  

 

 

 

The key to CRPS/RSD pain will apply to all forms of chronic pain, in particular the most difficult form, neuropathic pain. RSDSA funds research into all forms of chronic pain, not only Complex Regional Pain Syndrome (CRPS/RSD). Their scientific board members are not funded by opioid money.

 

 

 

Exactly

what is the annual cost of care

as fraction of GDP

for the growing population of Americans on opioids

for one year, for lifetime?

 

 

People are dying from prescription opioids and those who need them find they don’t work well enough. Prescriptions opioid costs must be a huge fraction of the medical costs in the United States GDP. You are required  to see a doctor every single month each year, often lifelong, just for one opioid, 12 months a year x 30 years x tens of millions of people and increasing – a growth industry. Not even counting $600 a day for the opioid, what the cost of monthly visits for 30 years? Not counting the army of DEA, FDA, CDC agents watching the opioids like a hawk. We all have to be sharp, addiction is growing. Addiction aside, deaths from prescription opioids are shaking up the CDC forcing urgent change this coming month.

 

 

 

Opioids do not work well for chronic pain

We need better

It’s not just the $600/day price

They just don’t work

 

 

donate

 

 

Raise a joyful noise at NIH now or write back at us readers with comments and better suggestions. Tell others what you’d like to see. Which politicians do you know would be most interested in this at national levels and organizations?

 

You may never see this change unless you do it now. Other forces will get this new money.

 

 

Turning point now

May not return

 

 

We are at a turning point and we will fail to catch the sail that’s coming fast to carry all research money in their shiny big stem cell direction. They never look back.

 

 

There is so many medications we can use today, FDA approved drugs that can be re-purposed and applied to recent cutting edge science. Someone must pay to do the work to study this.

 

 

Re-purpose old drugs

 

 

Stanford just showed a popular generic drug improved recovery of stroke paralysis in mice to begin at 3 days rather than 30. Old drug, new purpose, of course more years of testing to confirm in humans. Brilliant team applying new science.

 

 

Request
NIH to solicit a

Special Invitation

for 30 good protocols to

repurpose old drugs

 

 

Hundreds of old drugs, already approved, could be involved in mechanisms we have recently learned about. Speak up or money will go to shiny new stem cells. None for chronic pain or major depression. No company will find this profitable – it must be funded by NIH. A popular generic sleeping pill can bring astonishing return from stroke paralysis.

 

 

Congress has not opened this new money to NIH in many long years. How often will there be extra money?

 

 

donate

 

 

Lawrence A. Tabak, D.D.S., Ph.D.
Principal Deputy Director, NIH, solicits you to

Review the NIH Strategic Initiative Plan and their

Request for Information (RFI) and the NIH website

and provide your feedback via the RFI Submission site

 

 

This is for “stakeholder organizations (e.g., patient advocacy groups, professional societies) to submit a single response reflective of the views of the organization/membership as a whole. We also will be hosting webinars to gather additional input. These webinars will be held in early to mid-August.

 

 

 

Be the change you wish to see

Donate to those organizations

to solicit the change you wish to be

 

 

 

Happy New Year

Rejoice!

There’s money at NIH

 

 

 

 

 

 

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.

Relevant comments are welcome.

If any questions, please schedule an appointment with my office.

This site is not for email.

~~~~~

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

 

 

 

 

Bisphosphonates for Pain – Back Pain, CRPS Pain. Have You Received Pamidronate or Other IV Bisphosphonate for Pain?


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Bisphosphonates have been used for treatment of pain.

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I have reviewed a few studies on pamidronate infusions for pain,  below.

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Based on these small studies, there is a growing rationale for use of I.V. pamidronate in the setting of selected chronic intractable pain syndromes.

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Have you received IV Pamidronate or Reclast or any bisphosphonate

for treatment of pain caused by any condition?

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Bisphosphonates are effective for reducing bone loss and, separate from that mechanism, they have been used to reduce pain in persons with various conditions including Complex Regional Pain Syndrome, ankylosing spondylitis, rheumatoid arthritis, chronic back pain, and other conditions.

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After you vote, if you wish to see results, click on the words “View results.” You do not need to sign in or give your email. Simply view results.

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If you have any experience with bisphosphonates even if for osteoporosis, please comment below. Do you know which academic centers are giving IV bisphosphonates for pain?

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The mechanism of pain relief is not clear and there are no standardized protocols for the use of bisphosphonates for pain, but relief of pain is believed to be separate from mechanisms related to bone.

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Many patients have no other options for treatment. There are no large randomized controlled studies – where is NIH funding for pain?

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Many medical treatments do not work for some patients with Complex Regional Pain Syndrome or for chronic low back pain. When all else has failed, pamidronate may be given IV, often in a series of infusions that take up to four hours. There may be some flu-like symptoms for 1 to 3 days after.

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For reasons unknown to us, Complex Regional Pain Syndrome is often associated with bone loss in the area of pain. It is more marked and prolonged than in immobilized trauma patients.

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What dose should be used, how often should it be given? Few studies have been published.

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MEDICATIONS for OSTEOPOROSIS

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Bisphosphonate therapy is commonly used for diseases of bone such as osteoporosis or Paget’s Disease, multiple myeloma, bone metastasis, osteogenesis imperfecta, fibrous dysplasia. For example alendronate (Fosamax) or residronate (Actonel) tablets,  pamidronate infusions,  or others.  Zoledronic acid (Reclast) is given IV, usually only once each year. One form of ibandronate (Boniva) is also given IV, usually every 3 months.

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Other medications that are not bisphosphonates are used for osteoporosis such as calcitonin-salmon (Miacalcin) SC or IM injections, Forteo (rhPTH ) SC injections, or estrogen.

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MECHANISM of BISPHOSPHONATES

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Bisphosphonates slow the rate of bone loss, they do not actually build bone. Bone requires a balance of osteoblasts that form new bone, and osteoclasts that resorb bone. Osteoporosis occurs with age and especially with loss of estrogen that dramatically increases loss of bone. Other factors that lead to bone loss are lack of exercise, hormonal, nutritional and genetic predispositions.

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RISKS of OSTEOPOROSIS

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Some of the worst pain I have seen in my career is pain due to fractures of fragile osteoporotic bones. It may be impossible to treat. With osteoporosis, you may simply roll over in bed and 7 rib fractures occur. One woman developed hundreds of fractures throughout her pelvis and was bedridden for years after a very minor incident. Bone stimulators did not help and she could not walk or stand without help. Years later there was a 1-1/2 inch gap between the fractures in her pelvis and of course being inactive and bedridden can only make osteoporosis worse.

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RISK of MEDICATION for OSTEOPOROSIS

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Osteoporosis is more dangerous by far than any medication used to treat it. As with any drug, the benefit must outweigh side effects. Bisphosphonates increase bone thickness and reduce risk of fractures. Osteoporosis medications causes less than 1% risk of bone fractures. Fractures from the medications may be seen in the midshaft of the femur which is the mid thigh; and they may cause osteonecrosis of the TMJ, the jaw bone. Serious problems with bone healing after dental surgery may occur in those who take bisphosphonates. But the risk of osteoporosis is far greater than this small risk.

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Non-bisphosphonates also have dangers: Calcitonin may increase risk of cancer. PTH is the only one that can actually build bone – an anabolic agent that induces bone formation, not just prevent resorption of bone, but abrupt termination leads to rapid loss of bone density. Estrogen increases risk of clotting, thromboembolism that is a risk for stroke.

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Neridronate is a new bisphosphonate available so far only in Europe the last few years. They are making claims that a series of neridronate infusions can reduce pain 100% in persons with Complex Regional Pain Syndrome. That seems highly unlikely:  100% effective? Really? Oh, and so far no reports of necrosis of bone. But it has not been available as long as pamidronate, so it may be years before we get a better assessment of this drug that is confirmed by other laboratories.

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PUBLICATIONS

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Dr. Pappagallo published three of the studies below. He is one of the foremost scientist-pain specialists in the world.

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A pilot trial of intravenous pamidronate for chronic low back pain

PAIN, Volume 155, Issue 1 , Pages 108-117, January 2014,  Pappagallo et al, found no serious adverse events.

They tested four groups of 11 subjects (7 active, 4 placebo) at differing doses. They conclude:

i.v. pamidronate, administered as two 90 mg infusions four weeks apart, decreased pain intensity for 6 months in subjects with CLBP.

[Pain was decreased by > 4 points. They showed no relationship between bone density and analgesic response, but did find a relationship between PTH, vitamin D status and pain response.]

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Bisphosphonates are known to have significant analgesic activity in addition to their well-characterized role in inhibiting bone resorption. For example, pamidronate (Aredia®, Novartis), an aminobisphosphonate, demonstrates clinically significant pain relief when administered intravenously for the treatment of Paget’s disease, metastatic breast cancer and osteolytic lesions of multiple myeloma [5], [24], [51]. In addition, i.v. pamidronate has been shown to have analgesic activity in a wide variety of painful conditions, including complex regional pain syndrome [12], [44], [53], fibrous dysplasia [10], recurrent multifocal osteomyelitis [22], [35], ankylosing spondylitis [33], rheumatoid arthritis [31], and others (for review, see [49]). The mechanism(s) of this analgesic effect is not fully known, but antinociceptive effects of pamidronate and other bisphosphonates have been reported in animal models of pain [7], [8], [25], [52]. Inhibition of osteoclast proton secretion and other cellular and molecular mechanisms may contribute to the analgesic effect [37], [54].

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The molecular mechanisms of pamidronate’s analgesic effects are not fully understood. Bisphosphonates are known to inhibit the activity and/or cause apoptosis of osteoclasts [20], [46], which remodel bone by creating an acidic microenvironment via the release of protons through vacuolar H+-ATPase [6], [45]. Osteoclast-induced high concentrations of protons may activate acid-sensing ion channels and transient receptor potential vanilloid type 1 channels expressed by small nerve fibers involved in pain signal transmission [37], [42], [54]. Osteoclasts appear to have a role in inflammatory pain adjacent to bone and in the hyperalgesia observed in type IX collagen-deficient mice [2], [37]. Of interest, inhibition of osteoclasts by bisphosphonates in a rat model of degenerative joint disease has recently been found to prevent subchondral bone resorption and cartilage loss, and decrease pain [50]. Clinical findings may also suggest a role for subchondral bone changes in the early development of painful osteoarthritis [13], [36]. Furthermore, the anatomical core structure of the spine is made of bone tissue, and immunohistochemical studies have revealed the presence of a widespread network of peptidergic small sensory fibers throughout the bone marrow, mineralized bone, and periosteum [28], [32]. Thus it is conceivable that: a) nonspecific low back pain (associated with degenerative disk disease or spondylotic disease as in our study population) may be related to sensitization of bone nociceptors, plausibly in the context of subchondral bone resorption (eg, at the vertebral endplates and/or facet joints) and b) inhibition of subchondral osteoclasts (and possibly of other phagocytic or inflammatory bone resident cells) by i.v. pamidronate might be clinically relevant to the treatment of CLBP.

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The responder rate for pamidronate 180 mg increased from 50% at 24 hours after the second infusion to 100% at month 2; the 100% responder rate was maintained at all subsequent time points. [There were 7 patients in each group of this small study.]

(Fig. 3) illustrates that all subjects receiving 180 mg pamidronate had at least 50% pain relief at both 3 and 6 months postinfusion, and approximately 80% of subjects receiving 180 mg pamidronate had 100% pain relief at 6 months.

Fig. 3. Continuous responder analysis. Blue solid line, placebo; red dashed line, 30 mg pamidronate; green dashed/dotted line, 60 mg pamidronate; brown dashed line, 90 mg pamidronate; purple dashed/dotted line, 180 mg pamidronate.

 

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Pamidronate treatment in rheumatology practice: a comprehensive review

Clinical Rheumatology, Volume 28, Issue 12, pp 1359-1364, December 2009, Slobodin et al. from Israel.

The efficacy of pamidronate in patients with spondyloarthropathies; synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome; hypertrophic osteoarthropathy; osteoporotic vertebral fractures; chronic back pain due to disk disease or spinal stenosis; Charcot arthropathy; transient osteoporosis; and complex regional pain syndrome-I, has been demonstrated in more than 40 reports, the majority of which, however, were not controlled studies. In some of reviewed conditions, aside from providing analgesic relief, pamidronate may also have disease-modifying properties. While used in different doses in a variety of rheumatic disorders, pamidronate was generally reported to be well tolerated with an overall good safety profile. Pamidronate may represent an effective and safe choice for a spectrum of rheumatic patients, suffering from intractable musculoskeletal pain, unresponsive to traditionally recommended therapies. Large randomized, controlled studies examining the efficacy of pamidronate in the rheumatic conditions are urgently needed.

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Complex regional pain syndrome (CRPS/RSD) and neuropathic pain: role of intravenous bisphosphonates as analgesics. ScientificWorldJournal. 2008;8:229–236Yanow J, Pappagallo M, Pillai L.  They review multiple studies for pain of CRPS.

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Efficacy of pamidronate in complex regional pain syndrome type I. Pain Med. 2004;5:276–280, Robinson JN, Sandom J, Chapman PT from New Zealand.

Pamidronate 60 mg iv was given only one time to 14 patients, 13 placebo controls.

Overall improvements in pain score, patient’s global assessment of disease severity score, and physical function (SF-36) score were noted in the pamidronate group at 3 months, and improvements in role physical (SF-36) score were noted at 1 and 3 months. There was variability in pamidronate response among individuals. CONCLUSIONS: Pamidronate may be a useful treatment option in the management of patients with CRPS Type I. Although treatment response was variable, the majority of patients improved.

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Treatment of chronic mechanical spinal pain with intravenous pamidronate: a review of medical records. J Pain Symptom Manage. 2003;26:678–683, Pappagallo M, Breuer B, Schneider A, Sperber K.

[They] reviewed the charts of 25 patients who had experienced disabling spinal pain for several years, and whom we treated with [iv] pamidronate. None had a history of osteoporotic vertebral fractures or metastatic disease. Pain rating scores decreased in 91% of patients: on a 0–10 numeric rating scale, the mean pain change was 3.6 points and mean percentage change was 41% (P <0.0001).

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Treatment of severe, recalcitrant reflex sympathetic dystrophy: assessment of efficacy and safety of the second generation bisphosphonate pamidronate. Clin Rheumatol. 1997;16:51–56, Cortet B, et al. from France infused 14 patients 1 to 3 days, followed 3 months and in one case for 9 months. “results suggest an efficacy” and they recommended double blind placebo controlled studies.

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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 illegal for me to give medical advice

without seeing you in office for history and examination.

I cannot respond to your medical questions unless you schedule an evaluation.

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

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Treatment for Pain Could Last Months: Botox & Tetanus Chimera Injection


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Professor Bazbek Davletov now at Sheffield University, UK, reports his research that is featured on the cover of the October 2013 journal Bioconjugate Chemistry. He hopes the drug will cost around £1,000 a year, making it cheap enough for use on the NHS. It is authored by a 22-person team from 11 research institutes, including Lincoln University UK based Dr Enrico Ferrari.

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Dr Ferrari joined the School of Life Sciences in October last year from the Medical Research Council’s Laboratory of Molecular Biology in Cambridge, where he took part in the development of a new way of joining and rebuilding molecules in the research group of Professor Bazbek Davletov who was then at the MRC.

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Taking components of clostridium botulinum and clostridium tetani neurotoxins – known as Botox and tetanus toxin – they re-joined the molecule proteins using a ‘protein stapling’ technology targeting central neurons without unwanted toxic effects.

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Science Daily announcement:

‘Chimera’ Protein Could Lead to Drug Treatments for Chronic Pain

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Lincoln University, UK, heralds this promising discovery:

Scientists synthesise new ‘chimera’ protein which could herald future drug treatments for chronic pain

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“Scientists have manufactured a new bio-therapeutic molecule that could be used to treat neurological disorders such as chronic pain and epilepsy.”

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The molecule was able to alleviate hypersensitivity to inflammatory pain.

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“Dr Ferrari, who is one of the lead authors of the study, said: “The toxins were split into parts so they were unable to function. Then later they were reassembled using a ‘zipping’ system so they can operate in a safe way. The re-engineered chimera toxin has very similar characteristics to Botox and is still able to block neurotransmission release, but the paralytic effect is a lot less. We then added a tetanus molecule which targets the chimera to where the pain signals travel towards the central nervous system.””

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“Dr Ferrari added: “Many painkillers relieve the pain temporarily and have various side effects. The selling point of this molecule is that the pain relief could last up to seven months….””

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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.

~~~~~

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.

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

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PeaPure – Palmitoylethanolamide for Nerve Pain or Migraine


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PeaPure is a glial modulator. It is available in Italy and the Netherlands as a food supplement and has been studied in multicenter clinical trials in Europe for several years. It is well tolerated with no side effects and is very helpful for neuropathic pain, headache, and osteoarthritis. It is anti-inflammatory and neuroprotective.

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Because it inhibits astrocyte activation and the over-expression of pro-inflammatory molecules and signals, it is being investigated in Alzheimer’s Disease.

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The mechanism of action of PEA was discovered in 1993 by Nobel laureate Rita Levi-Montalcini in her work on nerve growth factors. She found it is involved in metabolism of mast cells and published a series of papers on its self-healing effect of the body in response to inflammation and pain. Two recent publications from Jan M Keppel Hesselink, MD, PhD, and his colleagues at the Institute for Neuropathic Pain, Amsterdam, The Netherlands, describe case reports, one of which is the case of a woman with CRPS.

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The purpose of this post is to clarify dosing of PeaPure and how to take it for a sudden flare of pain. My apologies for failing to recall the source of these instructions which I believe was from the manufacturer and from here and here. The latter includes an excellent review of its mechanism.

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Description of PeaPure® 400 mg capsules
PeaPure® is a food supplement based on a natural and fatty-acid like compound.
The substance palmitoylethanolamide (PEA) is a physiologically active molecule that the body produces naturally.
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What the user should know prior to ingestion:
•    There are no known significant side effects.
•    PeaPure® can be taken simultaneously with other medicine. In case of doubt, it is recommended to first consult your doctor or a pharmacist.
•    Use during pregnancy is NOT recommended.
•    PeaPure® does not contain sugar, yeast, allergens, sorbitol, magnesium stearate, povidone or other ingredients.

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Dosage and administration – please refer to the manufacturer.

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UPDATE SEPTEMBER 2014

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It is with a heavy heart that I report this news:

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Palmitoylethanolamide is

now available only from the Netherlands,

sold as PeaPure, a food supplement.

  It is no longer able to be imported by a pharmacy, but we are hoping

that may change if we can interest a supplement manufacturer to make it available for the US.

Patent rights, attorneys are far beyond the resources of my local pharmacy.

 

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I have published this year, 2014, on the treatment of

vulvodynia and proctodynia with PeaPure and a topical cream.

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There are no studies to show us how often it may relieve nerve pain, but it is astonishing when it works. No toxicity, no side effects. Your brain makes it, plants make it. There is a growing literature on it and I have posted on some of its mechanisms. And in particular, its Anti-inflammatory, Analgesic, Neuroprotective Mechanisms.

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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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~

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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Spine Fusions: No Better Than Cognitive Behavioral Therapy & Exercise


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Spine Fusions: no better than Cognitive Behavioral Therapy and Exercise

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This reportfrom the Academy of Neurology may help guide you in decision making: 

Deaths, Complications, Higher Costs Accompany Increase in Complex Spine Fusions Among Elderly.

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“Fusion is usually performed for degenerative disc disease for chronic low back pain, but a number of studies have shown that their outcomes are no better than a combination of graded exercise and cognitive behavioral therapy.”

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Tragically, dementia can result from extensive spine surgery. Many factors can contribute to that. If I were having spine surgery, I would look at the data of dementia following open heart surgery and the protective benefits of ketamine given prior to surgery. Ketamine can spare neuronal function. It is neuroprotective. I link to a publication on that in this post. The problem may be that so few physicians are willing to provide ketamine as they may lack information on its use, yet it is one of the safest medications we have, nontoxic and neuroprotective.

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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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Ketamine Intranasal for Rapid Relief of Pain and Depression


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Poorly managed pain can evolve into chronic disease of the nervous system

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Ketamine is an important analgesic, more important than opioids. It can dramatically reduce pain, and rapidly relieve depression and PTSD.  Please read my earlier posts here and here. And the NPR report here just after I posted this (skip to their last section). Yes, it is FDA approved and legal. One woman said:

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 ‘It was almost immediate, the sense of calmness and relaxation.

‘No more fogginess. No more heaviness. I feel like I’m a clean slate right now. I want to go home and see friends or, you know, go to the grocery store and cook the family dinner.’

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NPR again reports ketamine’s rapid relief of depression. A 28 year old man whose refractory depression began at age 15, after ketamine, says:

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‘I Wanted To Live Life’

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Stephens himself has vivid memories of the day he got ketamine. It was a Monday morning and he woke up feeling really bad, he says. His mood was still dark when doctors put in an IV and delivered the drug.”Monday afternoon I felt like a completely different person,” he says. “I woke up Tuesday morning and I said, ‘Wow, there’s stuff I want to do today.’ And I woke up Wednesday morning and Thursday morning and I actually wanted to do things. I wanted to live life.”.
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Since then, they treated him with Riluzole that is FDA approved for ALS and has one of the dirtiest side effect profiles I have ever seen in medicine with serious organ toxicity. Ketamine rarely causes mild transient side effects, usually none. It appears the concern is how ketamine is used on the street with potential for abuse. I do not see ketamine abuse in my patients, some of whom are on opioids for pain or Valium family medicines from their psychiatrist. All of those have a greater potential for abuse, also not occurring in my patients. Pain and/or depression can lead to suicide.
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About 18 months ago, researchers at Yale found a possible explanation for ketamine’s effectiveness. It seems to affect the glutamate system in a way that causes brain cells to form new connections.
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Researchers have long suspected that stress and depression weaken some connections among brain cells. Ketamine appears to reverse the process.

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It would be of interest to see a case report of the bladder problems they mention. Is this in a single drug addict who used many unknown medications on the street? Several physicians have infused IV ketamine for persons with pain for many years, in far higher doses than I prescribe, with no report of any but transient minor symptoms.

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David Barsook’s 2009 review, reference below, describes changes that cause memory loss and brain atrophy with chronic pain, in particular, Complex Regional Pain Syndrome (CRPS), and they also occur with chronic depression:

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With the onset of chronic pain (including CRPS) a number of changes in brain function occur in the human brain including but not limited to: (1) central sensitization ; (2) functional plasticity in chronic pain and in CRPS; (3) gray matter volume loss in CRPS ; (4) chemical alterations; and (5) altered modulatory controls. Such changes are thought to be in part a result of excitatory amino acid release in chronic pain. Excitatory amino acids are present throughout the brain and are normally involved in neural transmission but may contribute to altered function with excessive release producing increased influx of calcium and potentially neural death.

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Brain atrophy and memory loss has also been shown in chronic low back pain as well as in chronic depression.

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Barriers to management of chronic pain are many:

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Although opioids are effective for acute pain, effective treatment of chronic pain is often daunting, particularly neuropathic pain.

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Opioids have been shown to create pain causing imbalance in the glial cytokines that favor pain rather than relief of pain. Opioids carry the risk of opioid-induced hyperalgesia which is a severe pain sensitivity. They affect the brain and endocrine system. Opioids may fail to offer significant relief, fail to improve function, and risk misuse, abuse, diversion and death. Their costs are astronomic, insurance coverage is increasingly limited, the potential for complications may be life threatening in a hectic medical setting, side effects can be lethal, lack of physician training in use of opioids and alternatives to pain control lead to increasing deaths, addiction and diversion. It has become a national emergency and a trillion dollar war on drugs.

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Complications can be greatly reduced through use of a scrupulous history and physical examination, but reimbursement is directly proportional to the shortest time spent with a patient. Will that help assessment and care?

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Individuals may have dramatically different responses to opioid therapy; some may not tolerate any, and relief must be balanced with side effects that increase as the dose increases. Patient status may change and require IV, rectal or tube delivery instead of oral formulas; drug-drug interactions may require rapid changes, and disease of kidney, liver or brain may require modifications or stopping altogether. They may increase risk of falls and cause central sleep apnea with drop in oxygen because the brain fails to give a signal to breathe.

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Chronic pain can lead to loss of sleep, hopelessness, depression, anger and other mood disorders such as panic, anxiety, hypochondriasis and post traumatic stress disorder [PTSD]. Treatment of mood disorders are shown to profoundly reduce pain perception and/or ability to cope with pain.

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Ketamine is anti-inflammatory and can reduce the need for opioid use, thus reducing the pain and side effects caused by opioids.

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Nasal ketamine is more effective than oral ketamine for pain relief; oral dosing has no effect on depression.

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Nasal delivery of ketamine is now possible due to advances in metered nasal sprayers that deliver a precise dose. No needle is required, no IV access, no travel to a specialist needed.

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You can carry pain relief with you and use it as directed when it is needed.

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Ketamine is an NMDA antagonist: it antagonizes the NMDA receptor which plays a profound role in pain systems and centralization of pain.

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Ketamine is neuroprotective and it can help other disease states as noted by Barsook, 2009:

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Besides improvement in pain, “there may be lessons from other diseases that affect the brain; it is noteworthy that acute ketamine doses seem to reverse depression and ketamine decreased prevalence of post-traumatic stress disorder (PTSD) in soldiers receiving ketamine during their surgery for treatment of their burns. In addition ketamine attenuates post-operative cognitive dysfunction following cardiac surgery that has been known to produce significant changes in cognition. [emphasis mine] The data suggest that the drug can alter or prevent other conditions based on its NMDAR activity where other drugs NMDA receptor antagonists are perhaps not as effective in these or pain conditions. Lastly, NMDA antagonists have been used in degenerative disease (and pain may be considered a degenerative disease as defined by loss of gray matter volume, see above) with mixed effects perhaps relating to how they act on specific NMDA subtypes. Taken together, ketamine may act not only on sensory systems affecting pain intensity, but also on a constellation of brain regions that are involved in the pain phentype. [sic, phenotype]”

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Side Effects

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Ketamine is more frequently used in babies and children than in adults because high doses of ketamine can induce hallucinations in the adult. Importantly, it is used in high dose in adults for treatment of Complex Regional Pain Syndrome.

Low doses, cause little or no side effects in adults. If present, they are transient and often resolve in 20 minutes. Patient who respond to ketamine report good acceptance as they find the relief of pain and/or depression far outweighs any short term minimal discomfort.

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Pain care reform is urgently needed.

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Research funding for pain is less than half of one percent of the NIH budget. More research is needed, but research on low dose ketamine for treatment of pain and depression has gone on for twenty years.

The public health crisis of untreated pain, which often results in disability, parallels the country’s struggle to halt the cost of health care. The longer a person remains with untreated pain, the less likely they are to return to work or to be employable.

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Conclusion

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Pain control requires urgent attention. It is past time to put into practice the use of this valuable medication so people can get on with life instead of being mired in chronic pain that for many risks suicide and ensures continuing decades of disability. Academic studies are usually limited by defining a predetermined dose rather than clinically titrating to effect. Thus no surprise, they find no effect as every patient will have no response until they reach their dose. And that dose, in my experience, falls into a bell shaped curve. One size does not fit all. Some respond at very low dose, others require much more, and the majority fall between.

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In my experience prescribing ketamine for ten years, only a rare person has problems. Almost all find it has returned function or significantly relieved pain. Some have been able to entirely eliminate opioids that did nothing for their pain for decades, though they dutifully returned to the MD every month to chronicle that pain. Pain continued to be rated ten on a scale of ten; patient always compliant despite side effects of constipation and often depression. My patients find the benefits of nasal ketamine far outweigh the relief of oral ketamine and at much lower doses with fewer side effects.

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Further, while the pain relief may be short lived, some find it gets better with repeat dosing, and relief of depression may last one to two weeks with a single dose.

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References

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http://www.wjgnet.com/1007-9327/10/1028.asp  Ketamine suppresses intestinal NF-kappa B activation and proinflammatory cytokine in endotoxic rats.

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CONCLUSION: Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-a and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B.

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http://informahealthcare.com/doi/abs/10.1080/J354v16n03_03  Ketamine as an Analgesic Parenteral, Oral, Rectal, Subcutaneous, Transdermal and Intranasal Administration

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Ketamine is a parenteral anesthetic agent that provides analgesic activity at sub-anesthetic doses. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with opioid receptor activity. Controlled studies and case reports on ketamine demonstrate efficacy in neuropathic and nociceptive pain. Because ketamine is a phencyclidine analogue, it has some of the psychological adverse effects found with that hallucinogen, especially in adults. Therefore, ketamine is not routinely used as an anesthetic in adult patients. It is a frequently used veterinary anesthetic, and is used more frequently in children than in adults. The psychotomimetic effects have prompted the DEA to classify ketamine as a Schedule III Controlled Substance. A review of the literature documents the analgesic use of ketamine by anesthesiologists and pain specialists in patients who have been refractory to standard analgesic medication regimens. Most reports demonstrate no or mild psychotomimetic effects when ketamine is dosed at sub-anesthetic doses. Patients who respond to ketamine tend to demonstrate dramatic pain relief that obviates the desire to stop treatment due to psychotomimetic effects (including hallucinations and extracorporeal experiences). Ketamine is approved by the FDA for intravenous and intramuscular administration. Use of this drug by the oral, intranasal, transdermal, rectal, and subcutaneous routes has been reported with analgesic efficacy in treating nociceptive and neuropathic pain.
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http://www.ncbi.nlm.nih.gov/pubmed/15109503  Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study  Daniel Carr, et al, 2004
Crossover, 20 patients. Ketamine reduced breakthrough pain within 10min of dosing, lasting up to 60min
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http://www.ncbi.nlm.nih.gov/pubmed/15288418  Safety and efficacy of intranasal ketamine in a mixed population with chronic pain
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The intranasal route for ketamine administration has been applied only for pain of dressing changes in a single case study (Kulbe, 1998). In this patient, oxycodone and acetaminophen were ineffective to control pain during burn dressing changes in a 96-year-old woman cared for at home. She tolerated the burn dressing changes after three intranasal sprays of 0.1 ml each, in rapid succession, each containing 5 mg ketamine (15 mg total) (Kulbe, 1998).
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http://www.acutepainjournal.com/article/S1366-0071%2807%2900167-2/abstract  Safety and efficacy of intranasal ketamine for acute postoperative pain
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Ketamine delivered intranasally was well tolerated. Statistically significant analgesia, superior to placebo, was observed with the highest dose tested, 50 mg, over a 3 h period. Rapid onset of analgesia was reported (<10 min), and meaningful pain relief was achieved within 15 min of the 50 mg dose. The majority of adverse events were mild/weak and transient. No untoward effects were observed on vital signs, pulse oximetry, and nasal examination. At the doses tested, no significant dissociative effects were evident using the Side Effects Rating Scale for Dissociative Anaesthetics.
The safety profile following treatment with ketamine was comparable to that seen with placebo.
Although patients did report side effects of fatigue, dizziness and feelings of unreality more often following treatment with ketamine than following treatment with placebo, no patient reported hallucinations and the side effects were generally reported to be of mild or moderate severity, and transient. No serious adverse events were reported and the incidences of associated adverse events were comparable for ketamine and placebo. Although study medication was administered intranasally, nasal signs and symptoms were few and inconsequential. A distinctive taste, however, was reported more often following treatment with ketamine than following treatment with placebo.In conclusion this randomized, placebo-controlled, double-blind study, in 20 patients, has demonstrated that intranasal ketamine is safe and effective for BTP [breakthrough pain]. Our findings augment an early but promising literature documenting the effectiveness of nasal administration of a variety of opioids for pain management in adults (Dale et al., 2002) .
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~http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875542/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875542/  Ketamine and chronic pain – Going the distance, David Barsook, 2009

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This important paper covers essential points not mentioned by many, thus quoted at length below:

“Ketamine, brain function and therapeutic effect – neuroprotective or neurotoxic

With the onset of chronic pain (including CRPS) a number of changes in brain function occur in the human brain including but not limited to: (1) central sensitization ; (2) functional plasticity in chronic pain and in CRPS; (3) gray matter volume loss in CRPS ; (4) chemical alterations ; and (5) altered modulatory controls. Such changes are thought to be in part a result of excitatory amino acid release in chronic pain. Excitatory amino acids are present throughout the brain and are normally involved in neural transmission but may contribute to altered function with excessive release producing increased influx of calcium and potentially neural death. Here lies the conundrum the use of an agent that potentially deleteriously affect neurons that may already be compromised but may also have neuroprotective properties by mechanisms that include reducing phosphorylation of glutamate receptors resulting in decreased glutamatergic synaptic transmission and reduced potential excitotoxicity . Alternatively, ketamine may affect glia regulation of glutamate and inhibit glutamate release within glia. However, by whatever mechanism ketamine acts on CRPS pain, there does seem to be a dose/duration effect in that longer doses at levels tolerated by patients seem to prove more effective in terms of the duration of effects.

So what could be happening in the brain and what is required to alter brain systems and reverse the symptomatic state? Ketamine may diminish glutamate transmission and “resets” brain circuits, but it seems that a minimal dose and/or duration of treatment is required. Alternatively, ketamine may produce neurotoxicity and damage or produce a chemical lesion of affected neurons. These two issues are important to be understood in future trials. Reports from patients who have had anesthetic doses have included prolonged pain relief for many months. While the authors did not address issues such as the effect of dosing duration or repetitive dosing at say 6weeks, they did show a level of efficacy based on NNT that equals or betters most drug trials for this condition.”

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“Conclusions

As a community we have a major opportunity to define the efficacy and use of a drug that may offer more to CRPS (and perhaps other) patients than is currently available. This is clearly an opportunity that needs urgent attention and a number of questions remain to be answered. For example, is ketamine more effective in early stage disease? How does ketamine provide long-term effects? Further controlled trials evaluating dose, duration, anesthetic vs. non-anesthetic dosing are needed. Few of us really understand what it is like to suffer from a chronic pain condition such as CRPS. Ketamine therapy may be a way forward that can be brought into our clinical practice through further controlled studies that will allow for appropriate standards for use in patients.”

 

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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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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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Ketamine


Ketamine for persons with severe pain

cancerIn special circumstances, I may suggest a trial of low dose oral ketamine. It is formulated by a compounding pharmacist as an oral suspension. It is safe to use without significant adverse effects, though you may experience transient symptoms lasting 20 to 40 minutes after the first few doses. For most people, it may relieve pain when all other methods have failed, possibly including total pain relief with no side effects in patients who have then been able to discontinue all opioids.

Keep all your medicine, opioids and ketamine, in a lock box to prevent abuse by others. This is a Schedule III drug like Vicodin.

Achieving control of chronic pain requires a partnership

based upon trust and effort

Requirements: I will work closely with you on ketamine and ask you to keep a log of pain before each dose and 30 minutes after. In addition, for the first week I ask that you log blood pressure and heart rate before each dose and 30 minutes after. This requires that you see me in the office one week later. If you have any questions or problems, I ask that you call me the same day, whether it be weekend or holiday. If you are unable to keep these logs before and after the dose, and the appointment one week later, the trial will be discontinued. You have no authority to continue without my consent.

Blood Pressure: Usually no change occurs in blood pressure. Some have reported that ketamine lowers their blood pressure and they are lightheaded when they stand up. If your blood pressure drops or if you are lightheaded, be very cautious as that may lead to fainting and brief loss of consciousness. Anytime a person faints, that could result in potentially serious injury such as hip fracture, other fractures, bleeding or brain injury if you strike your head. Your blood pressure should be above 100 when standing.  Ketamine has been reported to increase blood pressure and pulse, but I have not found that to occur with these doses.

Side Effects: Ketamine has a very narrow therapeutic window for pain control. This means that once you find the dose that relieves pain, a very slight increase in dose may produce intolerable side effects. Unfortunately some patients reach a dose that produces side effects before they experience any pain relief.

Most patients have no side effects with the low doses used by this protocol, though some may have mild symptoms lasting up to 40 minutes. If you do, then try decreasing the dose a small amount.

It is possible but rare that you may experience severe, frightening hallucinations or may feel you are outside the body observing it do things, called a dissociative reaction.

These side effects are dose related and have been short lasting, usually no longer than 40 minutes.  The antidote is Ativan.

Steps to follow: Read all steps carefully before you begin

  • Take ketamine 30 minutes prior to your other pain medication
  • For the first dose, remain seated or lie down for 20 minutes after you take the dose to avoid risk of falling. Do not take the dose and walk around.
  • A few persons have had severe imbalance lasting 10 or 20 minutes. This has resolved after the first few doses in those persons. It may not happen to you, so test with caution. If it has not occurred at the first dose, it is unlikely to occur at all.
  • Follow the dosing guidelines in the log I give you and which I repeat in this next step:
    Begin with 0.25 mL and increase by increments of 0.25 mL every 6 hours or longer than 6 hours, until you have some pain relief. Do not increase that dose or dosing interval.

Example: begin 0.25 mL, then 0.5, next 0.75, 1.0, 1.25, 1.5, 1.75, 2.0

If you have had no effect on pain by 2.0 mL, schedule an appointment for further instructions.
If your pain decreases only 1 or 2 points, that is your dose.  It will NOT get better by increasing the dose.  Stop increasing.

  • If you have intolerable side effects, you may use 1 or 2 Ativan tablets immediately as an antidote, and every 30 minutes, up to 5 of them.
  • CAUTION: Be alert to the opioid-sparing effects of ketamine!

This means that if ketamine relieves your pain, you do not need to take the opioid as that would be an opioid overdose and may cause serious side effects.

Reduce or temporarily stop your opioid medication if pain is gone after using ketamine.

This is why you take ketamine 30 minutes before the opioid. Some people have been able to completely stop all opioid medication due to pain relief from ketamine alone.

  • CAUTION: Do not drive for 6 hours after a dose.

This is for the protection of you and others. You may not be aware of very subtle side effects.

  • You may take a dose every 6 hours, or longer than 6 hours. Less is more.

If ketamine loses its effect, stop use for 2 or 3 days, then resume. It can be a fickle drug.  That is why increasing the dose causes loss of effect.

Some take ketamine only before sleep. If you do that, use it 30 minutes before sleep in order to log its effect and take blood pressure/pulse before and after. Continue this initially until further changes are approved.

Ketamine was approved for use as an anesthetic by the FDA in 1970

It’s use for pain is “off label” as it was approved only in high doses for anesthesia. It has been used safely in babies. Unlike opioids, it does not depress breathing or bowel function, and usually does not depress cardiovascular function. Since the late 1980’s, numerous scientific articles have been published on its use as a third line choice for some pain conditions; there are few double blind control studies, one is listed below. If you search ketamine on various internet search engines you find it is abused by addicts just as other drugs are. You find medical articles when you search the literature using Google Scholar or PubMed in the National Library of Medicine. If you find a medical article with adverse effects, let me know. I have spoken to leading brain and psychiatric researchers who have verified there are no lasting side effects from its use.

Many publications on ketamine use multi-day infusions at much higher dosages than the oral dosages in my protocol. Drexel University has treated over 3,000 patients with infusions of 40 mg/hour for 5 days with no lasting adverse effects. Even higher doses than that are used for surgical anesthesia. Ketamine is a powerful tool for treating pain.

Medical Publications


You can click and download each reference in blue below

High dose ketamine improves neurological outcome after stroke in rats, Reeker et al, Canadian J Anesth 47:572-578, 2000

Ketamine, Pasero C, McCaffery M, Amer J Nursing, 105:60-64, 2005
An excellent review, more clinical, easier to read than some more technical papers

Ketamine in Chronic Pain Management: An Evidence Based Review, Hocking & Cousins, Anesth Analg, 97(6):1730-1739, 2003This nine page article is the best comprehensive review of ketamine’s use in almost every known pain condition including post stroke pain.  Easier to read; a catalogue of pain syndromes and references.

Ketamine Stops Aura in Familial Hemiplegic Migraine, Neurology, 55:139-141, 2000 Two mechanisms may account for this. First, ketamine can increase cerebral blood flow, which may counteract the marked hypoperfusion induced by cortical spreading depression, as observed in migraine with aura. Second, in experimental animals, ketamine accelerates the  restitution of neuronal function after hypoxia.

Ketamine oral use in 8 chronic pain patients, Canadian J. of Anesthesia, 2004


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The Reflex Sympathetic Dystrophy Association library has many articles on RSD, CRPS and ketamine. Remember most of the articles are written for scientists and physicians.

From their library I particularly recommend the first article, below.  The last two are very technical but important new research.


Expectations of Pain: I Think, Therefore I Am, Jones-London M, National Institute of Neurological Disorders and Stroke

For pain mechanisms, read
Beyond Neurons: Evidence that Immune and Glial Cells Contribute to Pathological Pain States, Watkins L and Maier SF, Physiology Review. 2003;82:981-1011.

For pain mechanisms, read
Complex Regional Pain Syndrome (CRPS): Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-I (reflex sympathetic dystrophy),  Oaklander AL et al., Pain. 2006;120:235-243.

There is no link to the following double blind controlled research publication:

Mercadante S, Arcuri E, Tirelli W, Casuccio A. Analgesic effect of intravenous Ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. J Pain Symptom Manage 2000;20:246-252. Mercadante et al compared intravenous infusions of Ketamine (0.25 and 0.5 mg/kg) with placebo in a double-blind, crossover study of 10 cancer patients with neuropathic pain.

Please note that the free Adobe Acrobat Reader is needed to read some references.

You can download the free reader now.

~~~~~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. ~~~~~

Lumbar Epidural Injections & Sympathetic Nerve Blocks


Nerve Block Therapy for Low Back Pain: Show Me the Money and the Science, is the title of an article published in 2002, in the American Pain Society journal Pain.  The author reviewed current studies and questioned the value of lumbar epidural injections and sympathetic nerve blocks.

The scientific evidence to prove efficacy simply was not there.  More importantly, even with fluoroscopy and accurate placement of the needle, the solution reached the desired area only 26% of the time.  The author called for research to test efficacy.

From the current review, we must conclude that lumbar epidural steroid injections and sympathetic nerve blocks produce a large amount of money, with very little science to support their application. Does this mean they are useless? Obviously not; these techniques have some value in acute pain management and should not be completely abandoned. However, their use as a mainstream ( almost knee-jerk ) intervention for acute or chronic low back pain does not appear to be at all justifiable at the scientific level.

The fundamental recommendation is quite obvious. Those pain specialists who use these techniques on a regular basis need to support and initiate some clinical research trials that adequately test these procedures’ efficacy. Without this, the routine application of epidural steroid injections and lumbar sympathetic nerve blocks for acute or chronic low back pain is not evidence based. Therefore, when can it be recommended remains an empirical question.

More recently in March 2007, the American Academy of Neurology studied the issue in depth and published  Practice Guidelines on the Use of Epidural Steroid Injections to Treat Radicular [sciatic] Lumbosacral Pain.

They also found no Level A quality research and did not recommend routine use:

Based on the available evidence, the Therapeutics and Technology Assessment subcommittee concluded that

1) epidural steroid injections may result in some improvement in radicular lumbosacral pain when assessed between 2 and 6 weeks following the injection, compared to control treatments (Level C, Class I-III evidence). The average magnitude of effect is small and generalizability of the observation is limited by the small number of studies, highly selected patient populations, few techniques and doses, and variable comparison treatments;

2) in general, epidural steroid injection for radicular lumbosacral pain does not impact average impairment of function, need for surgery, or provide long-term pain relief beyond 3 months. Their routine use for these indications is not recommended (Level B, Class I-III evidence);

3) there is insufficient evidence to make any recommendation for the use of epidural steroid injections to treat radicular cervical pain (Level U).

This subject will be an intense topic of interest for the Anesthesiology Subcommittee at the annual meeting of the American Pain Society that meets in San Diego May 2009.   At best, epidural injections and nerve blocks are temporizing measures.  If the first one is less than effective, they are often done in a series of three.  One risk of frequent steroid injections is osteoporosis.

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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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