Norway Prioritizes Healthcare for Pain – A Note on Cosmetic Breast Surgery

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Hello Norway! I need an emoji to smile welcome!

Population 5 million – therefore data on pain can be obtained

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534 readers on these pages from Norway in the four years since 2012 got me curious.

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Norway Institute of Public Health is charged to prioritize healthcare for pain.

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Impressive! Very smart.

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“Chronic pain affects about 30 per cent of the adult Norwegian population.”

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In Denmark, “chronic pain patients had four to five times 

more in-patient days in hospital than the general population.”

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Cosmetic breast implants – one in five have nerve pain for life.

Implants must be replaced every 10 to 15 years.

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Surprise note from Irish physician on Norway- see below.

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Pain is the most common reason people see a physician. Pain is the most common cause of long term sick leave and disability in Norway, and likely in every first world country. Without doubt every investment in returning people to productive health relieves the burden on the entire country.

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The most common method of treatment is analgesic drugs, and, I would add, the most cost effective.

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Pain is more common in females than males. Cosmetic breast surgery is the most common gift to girls for high school graduation in America. It was of interest to find Norway’s statistics on that:

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In a Norwegian study of young, healthy women who had cosmetic breast surgery, 13 per cent reported spontaneous pain and 20 per cent reported pain when touched one year after surgery (23).” Ahhhh, but implants are a lifetime commitment and depending on style, must be replaced every 10 to 15 years.  Is pain compounded with each overlapping surgery? Scarring? Use of arms? What further issues arise once these women require breast cancer treatment? We know that after breast cancer treatment, chronic neuropathic pain affects between 20% and 50% of women. Obesity has been linked to chronic neuropathic pain developing after breast cancer surgery.

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. 13 per cent had pain after surgery

20 per cent one year later

7 per cent more than they did immediately following surgery –

Is risk compounded when replaced every 10 to 15 years for the next 70 years?

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One in five, 20 per cent with chronic lifelong nerve pain!

Insanity

How can they know? Show them prior to surgery.

 Informed consent: view a video interview of girls who developed nerve pain.

Can it be prevented? Or treat early?

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This is neuropathic pain, the hardest to treat. Miserable.

Light touch elicits intense pain.

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We all routinely underestimate risk of surgery. For true informed consent, it would be essential to show a video interview of girls with postoperative neuropathic pain, explaining the financial cost of chronic neuropathic pain the rest of their lives, how it affects use of the arms and ability to work, how many times they must see an MD every year for pills, how it may get worse over time, what type of pills are required – this educates the surgeons too on how to diagnose and treat nerve pain with sequellae of depression, anxiety, insomnia, and how it affects everyone in their family. Everyone suffers. Many are disabled and agitated by this intense nerve pain.

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How does stress and fear affect risk of cancer and other serious medical diseases?

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We know with rodents, from John Liebeskind’s research with an Israeli team at UCLA in the mid 70’s, pain profoundly increases spread of cancer resulting in quicker death from metastases. Pain kills. He lectured nationwide on this. I posted on his message just weeks ago, December 27. “Pain kills. A malefic force.”  “…pain can accelerate the growth of tumors and increase mortality after tumor challenge.”

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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.

 

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Twenty percent! Girls don’t know. How could they?

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Does cosmetic breast enlargement at such young age

increase

potential risk of  tumorigenesis, invasiveness, metastasis?

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Trauma (surgery) activates microglia lifelong. Glia never return to baseline.

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Microglia produce inflammatory cytokines –  inflammation.

Inflammation underlies almost all known disease.

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Does breast surgery, any surgery, increase risk of other known disease?

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What does inflammation do to endometriosis and autoimmune risks in this population?

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These are purely speculative thoughts. We cannot know until it is studied longitudinally and prospectively – if ever. Large breasts are very trendy. Obesity is very common; alas it is also pro-inflammatory.

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Postsurgical sequaellae can be extremely challenging. I will try to post two case reports in the near future. They are complex, enlightening, tangled, difficult to diagnose, post-surgical cases. The senior chief of surgery at Mayo Clinic had only seen two prior cases like it in this man who had laparoscopic prostate surgery many years before. Surgical sequaellae cannot be predicted. Large scale surgery in girls for cosmetic reasons have unexpected consequences. What is their cost decades from now?

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Norway Institute of Public Health has very nice data on drugs used, graphed vs time for men and women.  

 

Chronic pain in children and adolescents

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The incidence of chronic pain in children and adolescents is poorly mapped in Norway, but the consumption of analgesics and figures from other countries suggest that chronic pain is also common in adolescence (8). In the Health Interview Survey of 2005, parents reported that 6 per cent of children aged 6-10 years and 12 per cent of adolescents aged 11-15 years had chronic pain symptoms.

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A study of 12-15 year olds in South and North Trøndelag shows that 17 per cent suffered regularly from headaches, abdominal pain, back pain or pain in arms / legs (9). Consumption of analgesic drugs among Norwegian 15-16 year olds is high and has risen considerably since 2001 (10).

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Treatment

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Pain is probably the most common reason for patients to seek health care (26). A Swedish study found that 28 per cent of patients in general practice had one or more medically-defined pain conditions (27) – (my patients have at least 3 or 4). Corresponding figures are found in Denmark (28), where it has also been shown that chronic pain patients had four to five times more in-patient days in hospital than the general population (29). Corresponding figures for Norwegian conditions are unavailable.

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Irish physician comments on Norway

just minutes before writing about Norway! sweet coincidence. He posted on a case report I wrote in 2010 on Complex Regional Pain Syndrome (CRPS) and low dose naltrexone, (LDN).

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Dr Edmond O`Flaherty

an hour ago

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I am a primary care physician in Ireland. I have been prescribing LDN for 9 years and it has utterly changed the lives of hundreds of people. The main conditions I see are fibromyalgia, chronic pain, MS, various cancers, Crohns/UC, chronic fatigue/ME, several other auto-immune diseases and one case of Interstitial Cystitis where a 30-year woman had “a fire in her bladder 24 hours a day” and who was due to have a cystectomy (bladder replaced by a plastic bag!) a month later than when she came to me by chance and soon became well.

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TV2 in Norway made a film about LDN in 2013 which was seen by 10 % of the population. The number using it there went from 300 to 15,000 in a few months. It is now on the website of http://www.lowdosenaltrexone.org in America and I was the only doctor outside Norway who was involved. I agreed to partake if they subtitled it in English which they did.

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.Yes

Yes. Opioids cause pain. Naltexone relieves, and often resolves pain.

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My comment:

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Based on the work posted on these pages, RSDS.org sent scientists and specialists to my office in 2010. Over two days I introduced them to eight of my patients with years of intractable chronic pain, all of whom responded to low dose naltrexone, four of whom required treatment only one month with sustained pain relief   for years! RSDS is now funding a study on LDN for CRPS at Stanford.

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Norway has well known large cities, UNESCO heritage sites and this absolutely gorgeous small seaport village Reine on an island in the Lofoten archipelago, above the Arctic Circle. It was “selected as the most beautiful village in Norway by the largest weekly magazine in Norway (Allers) in the late 1970’s” and is visited by many thousands annually. “Lofoten is known for a distinctive scenery with dramatic mountains and peaks, open sea and sheltered bays, beaches and untouched lands. Though lying within the Arctic Circle, the archipelago experiences one of the world’s largest elevated temperature anomalies relative to its high latitude. Lowest temperature ranges from 28.4 to 35.6 degrees F.  The warmest recording in Svolvær is 30.4 °C (87 °F).

 

 

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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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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!

 

 

 

 

Analgesic Response to Ketamine Linked to Circulating microRNA in Complex Regional Pain Syndrome

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Analgesic Response to Intravenous Ketamine

Is Linked to a Circulating microRNA Signature

in Female Patients

With Complex Regional Pain Syndrome

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The ability to measure Micro RNS’s (miRNA) in blood looks like it may become an important tool someday once it is available for the clinic. It could be used to predict if your condition will respond to various medications.

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MicroRNAs are emerging as important modulators of various psychiatric (schizophrenia, bipolar disorder) and neurological conditions including pain, epilepsy, cognitive dysfunction, neuronal development, structure and function. “MicroRNAs are small, non-coding RNAs that act as post-transcriptional regulators of gene expression.“  miRNA’s can be affected by morphine and affected by other drugs. It is hoped that complex clinical phenotypes may be profiled in assays of peripheral blood and may predict response to treatment such as in this study. Ketamine is given for selected patients that have failed to respond to standard treatment.

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This research was published in Pain, June 2015, by Professor Schwartzman’s group at Drexel University. Seven of his patients with Complex Regional Pain Syndrome were ketamine responders and 6 were poor responders. They note that, “Although [ketamine] treatment is generally effective, approximately 30% of patients have an inadequate response to ketamine.”

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“Stability in circulation and dysregulation in disease state are 2 features making extracellular miRNAs useful candidates for biomarker discovery. Alterations in miRNA profiles have been reported for rheumatoid arthritis and systemic lupus erythematosus as well as for painful conditions such as irritable bowel syndrome, chronic bladder syndrome, endometriosis, and migraine. Cerebrospinal fluid from patients with fibromyalgia showed differential expression of 9 miRNAs.”

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Quoting directly from the article:

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Highlights

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•We studied ketamine treatment–induced miRNA alterations in blood from patients with CRPS.
•Differential miRNA expression was observed in whole blood before and after treatment.
•Before therapy, 33 miRNAs differed between responders and poor responders.
•Lower pretreatment levels of miR-548d-5p may contribute to higher UDP-GT activity.
•Circulating miRNAs can be potential biomarkers in predicting treatment response.

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From the Abstract

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Investigation of the mechanistic significance of hsa-miR-548d-5p downregulation in poor responders showed that this miRNA can downregulate UDP-glucuronosyltransferase UGT1A1 mRNA. Poor responders had a higher conjugated/unconjugated bilirubin ratio, indicating increased UGT1A1 activity. We propose that lower pretreatment levels of miR-548d-5p may result in higher UDP-GT activity, leading to higher levels of inactive glucuronide conjugates, thereby minimizing the therapeutic efficacy of ketamine in poor responders.

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Perspective

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This study suggests the usefulness of circulating miRNAs as potential biomarkers. Assessing miRNA signatures before and after treatment demonstrated miRNA alterations from therapy; differences in miRNA signature in responders and poor responders before therapy indicate prognostic value. Mechanistic studies on altered miRNAs can provide new insights on disease.

 

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From the Discussion

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Ketamine is also considered to be the prototype for a new generation of glutamate- based antidepressants that can alleviate depression within hours of treatment. Several biological measures have been explored to characterize treatment response and to gain insight into mechanisms underlying the rapid antidepressant effects of ketamine. A plasma metabolomics study in patients with bipolar depression suggested that the basal mitochondrial b-oxidation of fatty acids differed between responders and nonresponders to ketamine. Other studies have shown differences in baseline plasma concentrations of D-serine, serum levels of interleukin 6, and plasma levels of Shank3, a postsynaptic density protein involved in NMDA receptor tethering and dendritic spine rearrangement.

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Differences in the ability to metabolize ketamine because of interindividual differences and pharmacogenetic factors have been proposed to contribute to the varied responses to ketamine therapy and its clinical outcome. Similar conclusions have been drawn for patients with depression; plasma from patients with treatment- resistant bipolar depression who had undergone a single 40-minute infusion of a subanesthetic dose of ketamine showed that although NK is an initial metabolite, it is not the major circulating metabolite. This again suggests that other downstream metabolites of ketamine may play a role in the pharmacological effects of the drug. It is also known that (2S,6S)-hydroxynorketamine is an active and selective inhibitor of the a7 subtype of the nicotinic acetylcholine receptor; this activity was shown to contribute to the pharmacological responses associated with the antidepressant activity of (R,S)-ketamine. We postulate that in patients with CRPS, 1 factor contributing to resistance is an altered pharmacokinetic profile produced by enhanced elimination of active metabolites downstream of NK, which is mediated by hsa-miR-548d-5p. However, because we have relied on indirect evidence of a higher percentage of direct/indirect bilirubin in poor responders, indicating increased UDP-GT enzyme activity, additional studies investigating hydroxynorketamine and its downstream metabolites along with their glucuronide conjugates in plasma and urine will provide direct evidence for the role of miR-548d-5p in mediating response to ketamine therapy in responders and poor responders.

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They noted a significant difference in body weight between responders and nonresponders (heavier), but not in duration of disease and analgesic response to ketamine. Toward that end, they will publish separately upon

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… investigating the link between miR-34a, which showed 28-fold reduction in poor responders relative to responders (Table 2), and the neuroendocrine system….

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From the Conclusion

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Our studies showed that miR-548d-5p can regulate UDP-GT but not CYP3A4, suggesting that UDP-GT activity in responders and poor responders may be mediated by differences in the level of circulating miR-548d-5p. Lower levels of miR-548d-5p in poor responders before treatment could result in higher UDP-GT activity, leading to the production of more inactive glucuronide conjugates and faster elimination of active ketamine metabolites downstream of NK. Thus, the levels of hsa-miR-548d-5p could minimize the therapeutic efficacy of ketamine and pain relief. Differences in miRNA signature can thus provide molecular insights distinguishing responders from poor responders. High failure rates of drugs targeted to treat neuropathic pain warrant changes in approaches. Studies targeting well-defined patient populations for clinical trials will play a crucial in developing drugs that may be efficacious in a subset of patients. Extending this approach to other treatment and outcome assessments might permit stratification of patients for maximal therapeutic outcome.

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How frustrating it is for patients and family who must cope with an intractable condition such as pain or Bipolar Disorder or treatment resistant Major Depression that has failed all commonly prescribed medications. For all of them, we need changes in approach.

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“High failure rates of drugs targeted

to treat neuropathic pain

warrant changes in approaches.”

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Perhaps scientists reading this would comment upon how it may relate to tolerance as it differentially occurs in those receiving intermittent ketamine vs continuous intravenous infusion.

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Dysregulation of miRNA’s has been shown in psychiatric disorders including depression and schozophrenia, neurodevelopmental disorders, cognitive dysfunction,  epilepsy, chronic pain states with implication for the cause and treatment of these disorders.

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Research targeting miRNA’s as novel treatment for depression has shown that chronic fluoxetine, repeated electroconvulsive shock therapy, and acute ketamine have the capacity to alter hippocampal miRNA levels.

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It is hoped these tests may be available someday clinically as the cost of off-label treatment not covered by insurance is a great burden for those already disabled by intractable pain or treatment resistant depression.

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PUBLIC WARNING

warning reprinted with permission of Demitri Papolos, MD
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Ketamine is a controlled substance.
Administered improperly, or without the guidance of a qualified doctor,
Ketamine may cause injury or death.
No attempt should be made to use Ketamine
in the absence of counsel from a qualified doctor.

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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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This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

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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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