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. 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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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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RSD/CRPS, Multiple Sclerosis, LDN & Ketamine

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

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

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

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Thankfully a physical therapist suggested the diagnosis.

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Why is pain management not a required subject for physicians?

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

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

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Does it make you wonder why 11 were done?

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

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

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

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I will highlight only two of the new medications started.

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

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

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

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

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

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Now she indicates pain continues to improve.

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

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What is LDN?

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

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

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

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

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Naltrexone is a glial modulator.

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What’s that?!

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

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

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

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

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

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

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

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

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The material on this site is for informational purposes only.

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

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

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

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

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Ketamine IV vs Nasal Spray or Sublingual

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Patients ask me to compare IV ketamine to other routes of administration such as intranasal or sublingual. No one has done comparisons. Even if they had, every person is different and may have several pain syndromes.

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I have outlined one case below. One disadvantage of IV ketamine is the cost and the need to schedule for an IV treatment with your physician often weeks in advance. For some, this may mean setting aside two weeks to travel and make other arrangements. The alternative is carrying this low cost medication in your pocket and using as needed to relieve pain when you have pain, or to prevent pain when you know your activity will flare it.

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Ketamine is an important medication for pain.  It is considered a third line choice for pain relief, but it is almost a first line choice for Complex Regional Pain Syndrome, CRPS  – the old term is RSD. And I prescribe it for other conditions that have been refractory to treatment. But, far more than any other pain syndrome, pain from CRPS can be flared by emotional stress or minor injury and it can spread to other areas.

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Ketamine is a short acting medication. It is both analgesic and anti-inflammatory.

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Opioids create pain; ketamine not only relieves pain, it also relieves inflammation. In fact, opioids may prevent ketamine from helping at all.

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A small number of pain specialists in the USA, most at university centers, provide IV ketamine for CRPS. Not all people respond. A lucky few may get months of pain relief, but may require monthly boosters, i.e. it may be a short acting medication only during the infusion or it may offer relief for weeks or months but not years. I do not believe anyone has published comparisons showing duration of effect.

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I view ketamine as a short acting medication that requires other combination medications to “clamp” the relief and prevent pain from recurring.

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Here is a case report posted a few years ago of my patient who had 8 months of relief from IV ketamine. It was given 24 hours/day for 5 days in May 2007, followed by four hour IV boosters two days every month. Unfortunately all ketamine stopped having any effect after 8 months. I then added multiple medications that were selected because of specific mechanisms — no opioids, no ketamine — and she has been pain free since December 2009 on a single drug.

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CASE REPORT

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Today was the 5th visit in the last two weeks with an out of state patient who has had CRPS since 1999. She also has sciatic neuropathy, chronic lumbar pain after 360 degree spinal fusion, shoulder pain, and two types of headache. Medications are now significantly helping all pain syndromes.

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Before seeing me, she had had a total of 9 infusions of IV ketamine most of them given at doses of 300mg/hr — a very high dose. She had no side effects from ketamine. One of those infusions was given for 6 days over 4 hours each day. She had failed a lidocaine infusion at high dose. A spinal cord stimulator was reprogrammed 10 times, but only made pain worse.

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I then started her on a combination of medications. With addition of the first new medication, she had 50% improvement in the first 24 to 36 hours, that lasted beyond the relief from nasal ketamine that was also started. Unfortunately, on day 8, she and another family member, came down with a virus that causes headache and severe vertigo. Nevertheless, all pain is markedly better.

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With ketamine she is able to reduce pain down to 1 on a scale of 10 for a few hours. Best of all she can carry it with her and use it as needed. She no longer needs to take two weeks out of her life to schedule IV ketamine infusions.

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It will take almost 3 months to slowly increase the other medications we started. Hopefully this combination will “clamp” the pain and prevent it from increasing so that she may become pain free without needing ketamine.

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After that, if she is able to become pain free, the plan is that we will then be able to slowly remove most of the new medications we started this week and still maintain relief of pain. I will see her again in the future.

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Sierra wildflowers

Click to embiggen

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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.

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For My Home Page, click here: 

Welcome to my Weblog on Pain Management!

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Pain and the Immune System – It’s Not Just About Neurons – Naltrexone

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The Immune System and Pain

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There is a whole new way of thinking of about pain that has nothing to do with pain being

transmitted by nerve cells in well defined nerve pathways.

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In the last few years, we have learned it has to do with activation of glia and the immune system.

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Pain is a central neuroimmune activation.

There is close interaction of nerve pathways and the central immune system.

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Neuroimmune responses parallel but do not always mirror peripheral immune responses.

The differences are critical.

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The science of understanding immune cell-glia and glia-neuronal interactions is in its infancy.

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What are glia?

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Glia are cells in the central nervous system (CNS), the brain and spinal cord. Ninety percent of the cells in the CNS are glia – microglia, astrocytes, oligodendroglia, perivascular glia. Glia outnumber neurons by almost 10 to 1.

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Microglia and astrocytes are immune cells that can release inflammatory responses with harmful effects on nerve cells such as inflammation, toxicity, and excitability. However, scientists are beginning to show that activation may also lead to good outcomes that are helpful for nearby glia and neurons, protecting against inflammation, toxicity and restoring normal pain signaling. In other words, they can restore balance.

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Beneficial and pathological microglia

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Neuroinflammation is a normal and necessary process in the acute phase, but not when it takes on a life of its own and creates persistent pain or disease directed against normal tissue (autoimmune response). They may fail to release protective agents (e.g. BDNF, Brain-Derived Neurotrophic Factor).

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Neuron-glia Tetrapartite Synapse

Glial activation from pro-inflammatory to anti-inflammatory state

(click image to enlarge)

Image from Milligan, E, Watkins, L. Pathological and Protective Roles of Glia in Chronic Pain,

Nature Reviews 10:23-36 (2009)

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Neuroinflammatory Disorders

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There is an growing body of evidence that shows many diverse diseases are characterized by neuroinflammation, such as Alzheimers, Parkinson’s Disease, ALS, Multiple Sclerosis, neuromuscular and myofascial syndromes and neuropathic pain, fibromyalgia, and chronic fatigue syndrome. There are research plans to show activation of glia in other conditions: Tourette’s Syndrome, dystonia, blepharospasm, and torticollis. A neuronal model no longer works to explain these conditions.

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What the heck is microglial activation and priming?

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How do glia become activated? They are always active, not activated but active, surveying their environment. Something must occur for them to become activated. Similar to a bee sting that primes your immune system, the first bee sting will not kill the person who is allergic, but BOOM! the second sting can kill. Glia can become primed by a first pain, but when pain next occurs, glia become activated and they respond faster, harder, longer.

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When activated, they change shape like amoeba and migrate to the site of injury or infection or stroke or dead cells where they proliferate, release cytokines, and phagocytose (consume) targets such as virus, dead tissue, important in wound healing. Microglia and astrocytes can release neuroexcitatory and pro-inflammatory products and growth factors for pain and hyperalgesia. See links to several recent publications on glia here, and mechanisms here and here. Microglia can repair the CNS. Or, an injury may heal and be long gone, but chronic pain may persist for years. How do we turn it off? The signal is no longer telling us about a new danger.

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The goal of research is to find ways to interact with the cascades of pro-inflammatory molecules and receptors to restore balance in the system. This is a major paradigm shift in treatment of chronic pain that has already led to many insights. Refer articles here.

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Toll Like Receptors

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Like all immune competent cells, glia have a myriad of receptors on their cell surface membranes. One of the more important are the Toll Like Receptors (TLRs) that are innate immune receptors in the CNS, discussed here. See image, below. TLRs “are key regulators of both innate and adaptive immune responses. The function of TLRs in various human diseases has been investigated….These studies have shown that TLR function affects several diseases, including sepsis, immunodeficiencies, atherosclerosis and asthma…. [They] may contribute to susceptibility to severe neonatal inflammatory diseases, allergies, and autoimmune diseases.” Other studies have shown “Toll-like receptors (TLRs) are essential in the host defense against infections. They also have functional roles in tumor progression and their ligands affect tumor cell proliferation, anti-apoptosis and immune escape. The expression or up-regulation of TLRs has been detected in various tumor cells.” “Dysregulation of these signaling pathways has severe consequences, and causes many autoimmune diseases and chronic pathological inflammation.”

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The Toll Like Receptors are not like other receptors. Not these snug little pockets where naltrexone binds. Instead the Toll Like Receptors are like an entire football field, with enormous nooks and crannies. Unlike other receptors, they have enormous interactions with many molecules and medications, e.g. naltrexone is a TLR4 inhibitor, an immune modulator, amitriptyline is a TLR4 inhibitor. And “Glial activation is now known to occur in response to opioids as well. Opioid-induced glial activation opposes opioid analgesia and enhances opioid tolerance, dependence, reward and respiratory depression.” That source is referenced here. Opioids create pain, not just the dread opioid induced hyperalgesia. Glia also contain cannabinoid receptors. Glia produce endogenous cannabinoids and they inactivate them.

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Toll-Like Receptors.

(Image courtesy of SABiosciences, click to enlarge)

Their action on IL-10 is key and more on that will be posted here later.

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Antibodies for pain?

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Some pain syndromes have been found to produce distinct antibodies.

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There is small but growing evidence that the immune system plays a role in Complex Regional Pain Syndrome, CRPS. These individuals have inflammatory markers in spinal fluid and tissue fluids. Recent studies have found antibodies against nervous system structures, specifically, “autoantibodies against an inducible autonomic nervous system autoantigen” in 30 to 40% of persons with CRPS.

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In 2010, a small study found that intravenous immunoglobulin (IVIG) can provide relief in a tiny percentage of patients. IVIG potentially interferes with those autoantibodies and reduces, i.e. downregulates, the inflammatory cytokines that are important in mechanisms of pain and hyperalgesia in the brain and the body. This study has many limitations but it is a first for IVIG.

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JJ Van Hilten et al have found HLA antigens associated with Complex Regional Pain Syndrome with fixed dystonia. “Our results encourage future studies to evaluate the role of HLA-B62 and HLA-DQ8 in different subtypes of CRPS.” This gene family has important immunologic functions.

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And, epidemiology studies show that persons with CRPS are more likely to have asthma.

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The study of glia is in its infancy but it is growing rapidly in many directions. There are drugs that can distinguish activated glia for targeted treatment, new methods of visualizing glia, new sites for pharmacologic intervention, and nanotechnology to deliver medication directly to the inflammation. ` More will come provided there is philanthropic support for this work. It is heartbreaking that NIH contributes less than half of 1% of its research dollar to pain.

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My thanks to the Reflex Sympathetic Dystrophy Syndrome Association, RSDSA.org, for sponsoring a workshop on Glia and Neuroinflammation that brought together the world’s foremost scientists and provided a unique forum for them to interact and learn from each other.

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It is hoped that their next workshop this year will be on imaging glia. We need to extend the work that has barely begun.`

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The material on this site is for informational purposes only.

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

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

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RSD – Complex Regional Pain Syndrome – A Case Report

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Rational Polypharmacy

Naltrexone is a remarkable drug for intractable pain

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I first saw this RN in June 2006.

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She is now 60 years old.  She was an OR scrub nurse for almost 30 years, but was disabled for the last 5 years before seeing me. She had Reflex Sympathetic Dystrophy [RSD] of both legs with “arthritis” of the feet/ankle that felt like she was “90 years old” with cold allodynia. Allodynia is pain from a stimulus such as light touch or a breath or air that is not normally painful. Imagine a light touch that feels like severe nerve pain, one of the most disturbing pains a person could have. The temperature of her feet was 81 degrees, hands 92 degrees.

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Pain of both feet felt like a vise grip, gnawing, penetrating, “like broken bones in the feet,” variable at different times but always worse as the day progressed, with a crushing sensation that penetrated through foot and ankle. She was unable to tolerate socks or anything on her feet after 5 pm, unable even to tolerate air on the area, unable to tolerate coolness below waist, but felt hot above waist. She wore a blanket and covers on the hottest 120 degree days, and forced herself to tolerate touch at the legs in order to desensitize them, as we instruct patients to do. She felt constant tingling numbness of the soles of feet for 3 years, with weakness, stiffness “almost solid” like a block. Spasm in soles of feet had resolved the last 6 months before seeing me.

Pain ranged from 2 to 9 on a scale of 10, where 10 is the worst pain imaginable, worst after 5 pm. Average pain was 3. It interfered with sleep at times, and she used a tented frame to keep blankets off her feet, preheated the bed to avoid any coolness, and avoided cold under all circumstances. In the morning, the joints felt like she had a broken ankle. She would massage the feet with lotion, put on alpaca socks, and slowly begin to walk. Then tried to mobilize the joints. Walking made pain worse though walking had always been a favorite activity.~

Before seeing me she had had more than 10 sympathetic blocks, was hospitalized 11 days due to headache from prednisone 60 mg that had been trialed to relieve her pain. She had been prescribed Procardia to relieve the “vascular” disease that she did not have but the drug led to gangrene of the gall bladder; she had been prescribed almost every “adjuvant” used to relieve pain and as much as 9 grams of Neurontin daily, all of this to attempt to relieve the severe pain in her legs and feet.

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This is how she got better

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When I first saw her in 2006, I prescribed low dose oral ketamine that gave relief lasting up to 3 hours from each dose. She then requested referral to Dr. Schwartzman, chief of neurology at Drexel University in Philadelphia, for continuous 5 day ketamine infusion that was done May 2007. She was pain free but it completely lost effect after 8 months, despite booster infusions every 4 to 6 weeks for 4 hours daily over 2 days during those 8 months. After insurance the cost out of pocket was $45,000 in 2007 alone. Dr. Schwartzman had nothing more to offer after it failed and said most patients have relief for less than 6 months if at all.

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In March 2007, I started her on a combination of Namenda 55 mg daily with lamotrigine 350 mg daily that relieved 90% of the pain, but once every 6 to 8 weeks she needed 12.5 to 25 mg low dose oral ketamine for breakthrough pain. Even more rarely, she used oxycodone 10 to 20 mg.

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In October 2008, adding naltrexone 1 mg by mouth, she became pain free. Since then she has not needed anything for breakthrough pain and on 3/5/09, she reported that her last use of ketamine and oxycodone occurred with the addition of low dose naltrexone.

 

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In 2009, she hiked 30 miles down the Grand Canyon and back up in 3 days.

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Naltrexone was later increased to 4.5 mg as she completely tapered off lamotrigine.

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By December 2009, the RSD was 98% better and she reported that it was not pain anymore. Medications then were naltrexone 12.5 mg at bedtime and Namenda 55 mg daily in divided doses. She had just a “remnant” of a little buzz, but no crushing except when active, late in the day.

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A few months later she slowly tapered off Namenda with no increase in pain; and in October 2010, on my advice she tapered naltrexone 12.5 mg from daily to every third day. There has been no increase in pain but she is reluctant to discontinue naltrexone for fear that RSD may recur.

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She hikes 2 miles 3 to 4 times a week, does Iron Mountain once a week, does “Silver Sneekers” exercise 1 hour 3 times a week and sleeps well 8 to 10 hours a night without a sleeping pill.

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She remains on low dose naltrexone as her sole medication for this

previously disabling neuropathic pain syndrome~

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She has returned to part time work and spends a few weeks a month traveling the world, hiking, volunteering, sightseeing.

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Research funding is needed to view whether we can detect

activated glia in the spinal cord, as discussed here.

If there are no signs of activated glia, she may feel reassured that the condition has resolved.

Naltrexone is an immune modulator.

The site of action of naltrexone is at the Toll-like receptor (TLR4) attached to the cell surface membrane of glia.

The ability to view activated glia would help greatly in treatment of so many conditions including neuropathic pain.

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Naltrexone

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I have found that naltrexone is a remarkable medication for various pain conditions, and going through the steps of rational polypharmacy may be very rewarding for some patients though at times it may work all on its own. It has caused me to completely reassess how I approach the treatment of intractable pain – not just RSD or CRPS but arthritis, sciatica and various forms of mechanical pain. And it has led to further changes in the timing and dosing of naltrexone based upon the experiences patients have reported back to me over the years. It is hoped that further research will lead to better understanding of how naltrexone acts upon pain pathways. Surprisingly we already know quite a fair amount.

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My deepest gratitude to Dr. Jau-Shyong Hong, Chief of Neuropharmacology at NIH, whose many generous discussions, emails and research publications have helped me to understand it’s profound anti-inflammatory effect in the central nervous system through its actions on microglia. I previously posted a discussion of mechanisms of naltrexone and dextromethorphan in greater detail here. Naltrexone and dextromethorphan are classified as morphinans, morphine-like. They suppress Superoxide, a free radical that destroys neurons which may cause or contribute to Alzheimers and Parkinsons Disease. That research goes back to the late 1980’s and continues to grow. Phase II studies with morphinans are now being done on those conditions. Studies are also going on now with naltrexone/Wellbutrin combination for weight loss. The drug is called Contrave, from Orexigen Therapeutics Inc. and the dose I believe is 32 mg naltrexone – I do not know how they decided upon that dosage.

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In my experience, naltrexone is a very benign drug at these low doses, though colleagues who prescribe 400 mg for the FDA approved use at that high dose may see some liver toxicity. I always begin at 1 mg or 4.5 mg, depending upon whether or not the patient is a slow drug metabolizer, i.e. may lack one of the CYP P450 chromosomes for metabolizing drugs. I have long suspected it also has an effect on the hypothalamus because a few patients with profound postmenopausal hot flashes have reported that is no longer a problem and that their husbands simply cannot believe the bonus, and this may explain the effect upon appetite that Orexigen has found. At higher doses than I generally use there may be some constipation which is treatable. It may cause vivid dreaming in some, and a small percentage may have insomnia for a few days. Pharmacology and safety is discussed here.

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Stay tuned. I’ll be adding more case reports of different pain conditions in the near future. They are truly fascinating. It has changed my entire approach to treating pain.

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Cost

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Wouldn’t it be nice if NIH funded more for pain research? Imagine how much money that would save the country and save the lives of each person with disability who could recover? As I posted here, the American Pain Society has shown that NIH spends 0.67% of its budget on pain research – less than 1% – though 10 to 20% of the population in the US suffers from chronic pain, an estimated 60 million Americans, and pain conditions are more prevalent among the elderly.

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I am told by my pharmacist that perhaps 70% of the time insurance will approve coverage for compounded low dose naltrexone. It is very affordable but some insurance carriers deny payment for naltrexone. Medicare will not pay for compounded medication either. Compare this low cost compound to the wholesale price for 100 tablets of Oxycontin, $1300, which may not be relieving pain – then multiple that by 2 or 3 each month for one patient. Imagine if the $22 billion of federal money for health insurance technology, for software which is untested and will expire in a few years, instead went into NIH funding for pain research. What a lovely thought.

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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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