Quell Neurodevice For Nerve Pain Will It Be Any Good

Today's post from diabetesselfmanagement.com (see link below) anounces another electro-stimulant device designed to reduce neuropathic pain. Not quite on the market (later this year), it reflects the growing interest in electro-neurostimulation but it has to be said that so far, results from these sorts of devices have been patchy to say the least. Maybe this one will provide more people with a positive result. It's lightweight and wearable and can be tracked with a smart phone, so these things at least stand in its favour. Time will tell.

CES Dispatches: Pain-Relieving Device for Diabetic Neuropathy
January 6, 2015 by Diane Fennell


(Quell[TM] Wearable Pain Relief Device [Photo: Business Wire])

Quell, a device that can relieve chronic pain in people with conditions such as diabetes, sciatica, and fibromyalgia, was unveiled this week at the 2015 International Consumer Electronics Show (CES), taking place in Las Vegas from January 6–9.

Roughly 60% to 70% of people with diabetes have some form of the often painful condition neuropathy (nerve damage), according to the National Diabetes Information Clearinghouse, and surveys of people with diabetes reflect rates of chronic pain ranging from 20% to 60%.

Created by NeuroMetrix, Quell is lightweight, wearable device that uses noninvasive neurostimulation technology to reduce chronic pain. The device, which has been approved by the U.S. Food and Drug Administration (FDA) for use without a prescription, can be worn both during the day and at night, and users will have the option of using their smartphone to track and personalize their pain treatment.

“Recent studies have shown that chronic nerve pain dramatically reduces the quality of life in people with diabetes,” notes Shai N. Gozani, MD, PhD, President and Chief Executive Officer of NeuroMetrix. “We believe that Quell may help many of these people reclaim their life from chronic pain.”

Quell is expected to be available for purchase by consumers later this year.

For more information, see the press release from NeuroMetrix.

http://www.diabetesselfmanagement.com/blog/ces-dispatches-pain-relieving-device-diabetic-neuropathy/

New Explanation For Diabetes Related Neuropathic Pain

Today's post from Sciencedaily.com (see link below) brings a dilemma with it. A study has shown that changes in 'dendritic spines' in the brain may play an important part in explaining neuropathic pain in diabetes-related cases! Yet nowhere does it say that this is exclusively a diabetes-related occurence. The article states that the reason why diabetes can cause neuropathy is still a mystery, so there is really no reason to assume that these changes in the nerve endings in the brain only occur in diabetes patients. We need the study to include HIV-related neuropathy and many other forms too, If the dendritic spines are not altered in other forms of neuropathy, then they have some important information but at the moment, to a layman like me, it's just not clear.
 Many people with HIV looking for information on neuropathy, may skip over articles about diabetic neuropathy because they think it doesn't apply. This is generally just not true. Most of the information about diabetic neuropathy applies to all neuropathies; it's just that diabetic neuropathy is by far the most common form amongst the general population. If you ask 99 out of a 100 diabetic neuropathy patients what their symptoms are, you'll find that they are exactly the same as your own. What the researchers mean to say is that they don't really understand the processes behind why neuropathy occurs in most of its forms and tying it to one disease depends on who their target readership is. If there are any experts out there who can explain (in relatively simple terms)  the real differences in disease-based neuropathies, please let us know - very many people are interested.

Unexpected Source for Diabetic Neuropathy Pain

ScienceDaily (May 15, 2012)

Normal dendritic spines — microscopic projections on the receiving branches of nerve cells — are shown at top compared to those of diabetic rat. At bottom, spines after receiving treatment. Yale study suggests that neuropathic pain associated with diabetes may be caused by reshaping of these spines in nerve cells, and might be treated by drugs. (Credit: Image courtesy of Yale University)

Nearly half of all diabetics suffer from neuropathic pain, an intractable, agonizing and still mysterious companion of the disease. Now Yale researchers have identified an unexpected source of the pain and a potential target to alleviate it.

A team of researchers from Yale and the West Haven Veterans Affairs Medical Center describes in the May 15 issue of the Journal of Neuroscience how changes in the structure of dendritic spines -- microscopic projections on the receiving branches of nerve cells -- are associated with pain in laboratory rats with diabetes.

"How diabetes leads to neuropathic pain is still a mystery," said Andrew Tan, an associate research scientist in neurology at the Yale School of Medicine and lead author of the study. "An interesting line of study is based on the idea that neuropathic pain is due to faulty 'rewiring' of pain circuitry."
With a growing number of diabetics, the condition represents a huge unmet medical need. Once neuropathic pain is established, it is a lifelong condition.

"Here we reveal that these dendritic spines, first studied in memory circuit processing, also contribute to the sensation of pain in diabetes," Tan said. A single neuron may contain hundreds to thousands of dendritic spines.

The Yale team led by Tan and senior author Dr. Stephen G. Waxman, the Bridget Marie Flaherty Professor of Neurology, professor of neurobiology and pharmacology,found abnormal dendritic spines were associated with the onset and maintenance of pain. They also found that a drug that interferes with formation of these spines reduced pain in lab animals, suggesting that targeting abnormal spines could be a therapeutic strategy.

Tan said that these dendritic spines in nerve cells seem to store memory of pain, just as they are crucial in memory and learning in the human brain.

"We have identified a single, key molecule that controls structural changes in these spines and hopefully we can develop therapeutic approaches that target that molecule and reduce diabetic pain," Waxman said.

Other authors on the paper are Omar A. Samad, Tanya Z. Fischer, Peng Zhao and Anna-Karin Persson,
The research was funded by the Department of Veterans Affairs.

http://www.sciencedaily.com/releases/2012/05/120515203056.htm

Shellfish Toxins For Nerve Pain

Today's interesting post is a press release from labspaces.net (see link below) and talks about something for the future of neuropathy treatment. It describes using liposomes, which are lipid spheres smaller than a red blood cell, to deliver powerful anaesthetics (sourced from shellfish) to the source of neuropathic pain. It still looks to be very much work in progress but is yet another sign that serious efforts are being made to research new nerve damage treatments and that can only be a good thing.

Putting a block on neuropathic pain before it starts

Tuesday, October 9, 2012 Thanks to Boston Children's Hospital for this article.

Using tiny spheres filled with an anesthetic derived from a shellfish toxin, researchers at Boston Children's Hospital and the Massachusetts Institute of Technology have developed a way to delay the rise of neuropathic pain, a chronic form of pain that arises from flawed signals transmitted by damaged nerves.

 The method could potentially allow doctors to stop the cascade of events by which tissue or nerve injuries evolve into neuropathic pain, which affects 3.75 million children and adults in the United States alone.

The researchers, led by Daniel Kohane, MD, PhD, of Boston Children's Department of Anesthesia and Robert Langer, ScD, of MIT, reported the results of animal studies online the week of October 8 in the Proceedings of the National Academy of Sciences.

Neuropathic pain can be long lasting and debilitating. Caused by shingles, nerve trauma, cancer and other conditions, it arises because damaged nerves send unusual signals to the spinal cord and the brain. The constant signaling effectively reprograms the central nervous system to react to any stimulus to the affected area, or even no stimulus at all, by triggering unpleasant sensations ranging from tingling and numbness to shooting, burning pain.

"Currently neuropathic pain is treated with systemic medications, but there has been significant interest in using powerful local anesthetics to block aberrant nerve discharges from the site of injury to prevent the onset of neuropathic pain," said Kohane. "Others have tried with varying degrees of success to do this in animal models using a variety of methods, but if applied clinically, those methods would require surgical intervention or could be toxic to tissues. We want to avoid both of those concerns."

The team's method combines saxitoxin, a powerful local anesthetic, and dexamethasone, which prolongs saxitoxin's effects. The two are packaged in liposomes—lipid spheres about 5.5 micrometers wide, or a bit smaller than a red blood cell—for nontoxic delivery to the site of nerve or tissue damage.

To assess whether the anesthetic-loaded liposomes (called SDLs for saxitoxin dexamethasone liposomes) might work as a potential treatment for neuropathic pain, Kohane and Langer—along with Sahadev Shankarappa, MBBS, MPH, PhD (a fellow in the Kohane lab) and others—attempted to use them to block the development of signs of neuropathy in an animal model of sciatic nerve injury. They found that a single injection of SDLs had a very mild effect, delaying the onset of neuropathic pain by about two days compared to no treatment. Three injections of SDLs at the site of injury over the course of 12 days, however, delayed the onset of pain by about a month.

The signal blockade mounted by the SDLs also appeared to prevent reprogramming of the central nervous system. The team noted that astrocytes in the spine, which help maintain the pain signaling in neuropathic patients, showed no signs of pain-related activation five and 60 days after injury in animals treated with SDLs.

"Ultimately we'd like to develop a way to reversibly block nerve signaling for a month with a single injection without causing additional nerve damage," Kohane explained. "For the moment, we're trying to refine our methods so that we can get individual injections to last longer and figure out how to generalize the method to other models of neuropathic pain.

"We also need to see whether it is safe to block nerve activity in this way for this long," he continued. "We don't want to inadvertently trade one problem for another. But we think that this approach could be fruitful for preventing and treating what is really a horrible condition."

http://www.labspaces.net/124304/_Putting_a_block_on_neuropathic_pain_before_it_starts_

Puffer Fish Poison For Nerve Pain

Today's post from smithsonianmag.com (see link below) talks about yet another poison (tetrodotoxin) from the animal world which may turn out to be useful in the struggle to control nerve pain. This time it's the Simpson's favourite - the Puffer fish, which kills a handful of trainee chefs every year. It's not such a stretch as you might think. Most animal poisons work by attacking the nervous system of their victims, so it's logical to assume that with modification, these poisons can be used to develop drugs which will act positively on the nervous system itself. Along with spiders, snakes, scorpions and others, this is the latest toxin which may be the answer to relentless nerve pain and that of course, affects all people living with neuropathy. Watch this space.

Pufferfish’s Deadly Toxin Could Help Chemo Patients
By Mary Beth Griggs smithsonian.com June 27, 2013

Researchers in New Jersey are working on an experimental drug that they hope will provide pain relief to cancer patients going through chemotherapy. The drug uses tetrodotoxin, the neurotoxin found in pufferfish.

Cancer is awful. And treatments for cancer, including chemotherapy, can be incredibly painful. Even the treatments for the pain, usually opioids like morphine, can be debilitating, with side effects like dizziness, vomiting, constipation and addiction.

Because of this, medical researchers are very interested in developing alternatives to opioid medications. Researchers at the John Theurer Cancer Center at Hackensack University Medical Center, in New Jersey, are working on an experimental drug that they hope will provide pain relief to cancer patients going through chemotherapy. The drug uses tetrodotoxin, the neurotoxin found in pufferfish.

In a statement, lead investigator Dr. Samuel Goldlust said, “Tetrodotoxin has been found to be 3,000 times more potent than morphine without the negative side effects of opioids.”

Tetrodotoxin is better known for providing a dangerous allure to foodies who enjoy living on the edge. Even though pufferfish contain enough of the toxin to kill 30 people, they are considered a delicacy—delicious if prepared correctly, deadly if not.

From io9:

chefs have to be trained for two years, during which they will eat many of the fish that they themselves prepare. And make no mistake, people do die from fugu poisoning. About five people a year make puffer fish their last meal, and many more get violently sick from it. It’s not a pleasant way to go.

The poison, tetrodotoxin, is actually produced by the bacteria that the fish allows to colonize its various parts. Tetrodotoxin is a neurotoxin, meaning it takes out the nervous system as it moves through the body. This may sound like a relatively painless death, with the brain going offline quickly. That’s not the case. The toxin starts with the extremities. The first place people notice it is in the lips. Then the fingers. There’s a tingling numbness, and a loss of control. This is a sign that it’s time to get to the hospital. The toxin moves inwards from there, taking out the muscles, often causing weakness, while paradoxically bringing on vomiting and diarrhea. Then tetrodotoxin hits the diaphragm. This is the large, muscular membrane in the chest that lets the lungs breathe in and out. The respiratory system is paralyzed while the person is still fully conscious. Eventually the toxin does get to the brain, but only after the person involved has felt their body being paralyzed completely, entombing them inside. Even then, some people aren’t lucky enough to completely lose consciousness. There are people who report being conscious, either occasionally or continually, throughout their coma.

The same qualities that make tetrodotoxin so deadly—taking out parts of the nervous system—are being harnessed by these researchers to block pain signals from parts of the damaged nervous system from getting to the brain. Forty percent of patients undergoing chemotherapy report having this kind of pain, and it is one of the more common reasons that patients will cite as a reason they choose to stop chemotherapy.

Dining on pufferfish, though, isn’t even remotely a good idea for chemo patients: The treatment developed by Goldlust and WEX Pharmaceuticals uses 300 times less toxin than is found in a single puffer fish and has a very long way to go before it is available to patients. It’s currently in a phase II trial (one of about 100-300 people, according to the FDA, which looks at how effective—and, extra key in this case, how safe—the drug is) and is being tested specifically on its ability to treat patients with “chemotherapy-induced neuropathic pain”—pain caused when chemotherapy treatment damages parts of the nervous system.

There’s two more phases after this, one before and one after the drug goes to market. Only about a third of experimental drugs make it through phases I and II of testing, and phase III is the most expensive and lengthiest part of the FDA approval process. But when dealing with painkillers, particularly painkillers that are based on deadly neurotoxins, it certainly makes sense to take the time to make sure the treatment is safe.

 http://www.smithsonianmag.com/smart-news/pufferfishs-deadly-toxin-could-help-chemo-patients-3446252/#hvJxYvYMcFAsV2B2.99

The Pitfalls Of Caring For Someone In Chronic Pain

Today's post from paincommunity.org (see link below) is a very useful article describing how difficult it can be to be a care giver for someone living with chronic pain. As many of you will know, neuropathy pain can reduce the quality of someone's life dramatically but not only the patient suffers. Their family and friends and the person who has had the responsibility of primary care thrust upon him or her, has to learn to adapt to a whole new relationship scenario and that can be very difficult indeed. Via the writer's own personal experiences, this article sums up the main problems and gives some hints as to how to learn to cope. Certainly worth a read if you're in that position, either as patient or carer.

“Angry, Sad and Frustrated”– The Unspoken Feelings of a Caregiver
Posted by Jim Stemple | March 19, 2014

As a caregiver to a very special lady for the last 20+ years I have learned it is ok to be angry and frustrated. This understanding did not come overnight.
Here is what I learned.
 
1: Chronic pain comes along and turns the lives of everyone involved upside down. Everything you knew is no more. Your life isn’t your life anymore, it is now a life filled with uncertain days and nights. You see the pain doesn’t only affect the person living with pain, it affects all those around them. It affects the whole household and those close to them outside the home. I may not live with chronic pain myself but I do live with someone who does and I am affected on so many different levels.

All the plans you had made for the future are put on hold or forgotten about. You find that each day life can and does throw something new at you and your loved one. It can be breakthrough pain, it can be a new health issue, insurance problems, finding a provider or just plain old frustration that threatens to blow the top of your head off.

The stress of not being able to know from day to day what the pain is going to decide to do to your loved one is over-whelming some days. As a caregiver you constantly worry what each day will bring.
 
2: Sometimes the one who is living with pain doesn’t realize how much it affects those around them. You see they are so consumed with trying to deal with the pain each day that sometimes they forget about the ones around them. The one living with pain will feel as if their partner/ caregiver doesn’t care enough, is angry at them or doesn’t believe that they “really have pain”.

But you know, it isn’t that at all. We, as caregivers, are pulled in so many directions that sometimes we think our heads may spin off of our necks. We do not know if we are coming or going—I know that I have felt that way.

3: For many partners/caregivers the financial stability of the family is always on your mind. For some families you lose the 2nd income that you were dependent on when your loved one is no longer able to work due to the pain. This can and does cause much discomfort and friction within the family. You don’t lay the blame on your loved one because they are unable to work but you cannot help but to feel frustrated at what the pain has done to your family and your dreams.

So what is the secret to success?

Over the years I have found that the most important thing is to communicate. It is ok for the caregiver to lose it once in a while. It is ok to be angry, sad, frustrated and overwhelmed. Share what you are feeling with your family or loved one. Let them know that you aren’t feeling all these things because of them, you are feeling all of this because of the situation—the pain and what it has done to the family and the one for whom you care so deeply.
Communicate with each other.

It is a two-way street. Share those feelings rather than holding on to the frustration, fear and anger. You are borrowing trouble that you nor your loved ones need, if you do not remain open. Holding in those nasty feelings may come back and haunt you– one day you are going to blow and it is not going to be pretty. Don’t wait until the fuse is lit because then things are said that hurt your loved one. Things that cannot be taken back no matter how much you wish you could.

I have been guilty of opening my mouth in frustration and saying some very hurtful things to her. Things that I didn’t mean and things that I wish I could take back more than anything. I am thankful because she knows that it is the anger and frustration talking and she can and does let my slips of hurtful words roll on by her and doesn’t dwell on them.

Trust me, we were not always like that but over the years we have learned to understand that the pain can make each of we say things that we truly don’t mean. We have learned that the pain is a vixen waiting for the right moment to spring forward and turn our lives in to a “he said, she said” fight of the century.

As a caregiver, I have found times where I feel torn between providing for the family and being there when I am needed. This push and pull really sucks! My job consists of taking me out of state each week. There are Mondays that I want nothing more than to stay at home and comfort her. Yet, I know that this will not happen, as I must be the provider which means leaving her and heading out to work. It doesn’t matter how much pain she is in. I have to leave her and go to work.

Yes, there are times she gets angry at me as she wants me there with her. It isn’t that I can really do anything to make the pain better. It is just knowing that she isn’t alone. I understand that but I am helpless to do anything about it. Even though she gets upset, I know she understands that if I could, I would never leave her alone.

As a caregiver, don’t you feel pulled and pushed in a hundred different directions at the same time? Do you find yourself angry, sad and frustrated because you want nothing more than to help your loved one? Would you take the pain from them in a heartbeat? I know I would. After all, I feel it was my job to protect her and help make her life a fairy tale come true.

The pain changes all that but remember even though you are angry, sad and frustrated you can make the world of difference for your loved one by just being there for them. You can make a difference by just listening, by holding their hand or giving a gentle hug when they need it the most.

Help find the humor in this world of pain and share it with them. You will be surprised how much laughter can help both of you. My special gal tells people all the time that if she had a penny for every time I have made her laugh we would be millionaires. That makes me smile.
Here is the pearl:

Remember the pain affects the whole family unit and it is up to everyone in that unit to make the best of the situation. Sure, you can choose to be miserable, depressed and find yourselves fighting all the time. A better option is to choose to communicate with each other and find the love, laughter and the ability to still see all that is good in your lives. Live the life that you want to live and refuse to let the pain destroy what means the world to you.

http://paincommunity.org/angry-sad-frustrated-unspoken-feelings-caregiver/

The Shoe Problem For Neuropathy Sufferers

Today's post from pamspaulding.net (see link below) is a personal story of a woman trying to find the best shoes to suit her neuropathy symptoms. Many people will identify with her problems and although the suggestions are of American shoe brands, it does highlight the fact that we need to find footwear that is both reasonably stylish and comfortable and supportive. That's not an easy task!

When you have neuropathy-damaged feet, good (cute) shoes are hard to find. 
Posted by Pam Spaulding Saturday, June 8, 2013

 The stereotype is that lesbians wear "comfortable" shoes, as in unfashionable, or maybe work boots, I have no idea.

 Anyway, this lesbian has serious neuropathy in both feet. I've had insulin-dependent diabetes for 30 years, and thankfully my eyes and kidneys -- usual targets of long-term damage -- are fine, unfortunately the feet are what took the damage. My blood sugars have been in good control, but it's hard not to have some long-term effects having diabetes for this long. BTW, it runs on both sides of my family -- both of my parents had adult-onset but were not obese. My brother is fine; I seemed to be the one to get all of the horrid metabolic and immune disorders passed down. Even my RA, according to my rheumatologist, was spawned through the genes; my mom had sarcoidosis, which is in the same auto-immune family.

 Anyway, it's hard to describe what neuropathic pain feels like -- it's simultaneously numbness paired with extreme sensitivity at times to the touch, such as feeling like you're walking on hot coals, or someone is stabbing you with little knives on the soles of your feet. The duality of this is both frustrating and annoying because it can ramp up at any time. The worst-case scenario is an attack of it at night -- I've had pain so bad that even having the sheet touch my feet under the covers was excruciating.

 On the other hand, my feet are nearly completely numb to hot or cold, which can be dangerous. Burning hot water feels only warm on them; ice barely registers as cold. The numb aspect also makes it easy to slip in the shower, since my feet don't have the correct sensation to grip the wet floor well. I have to have bath mats all over the floor to make it to my slippers.

 One of the few topical things that help is capsaicin, derived from hot peppers. Mostly this is used by folks with osteoarthritis. In treating neuropathy, the heat sensation generated by it cancels out/breaks up the neuropathic signals causing the pain. Kate tried using it on a sore muscle and she couldn't bear the burning sensation; I barely feel anything warm on my feet, but after about a half-hour, some of the worst burning subsides and I'm able to finally sleep.

 But back to shoes... 

 Almost all my old shoes -- nice dress shoes, sandals -- had to be tossed out over the last couple of years because they either 1) hurt my feet by causing neuro-pain, or 2) didn't provide enough shock absorption to prevent knee and hip pain that I have from RA. What's left to wear? Well, lots of styles that look like Grandma Shoes. At this point, the only brand I trust to be comfortable are Easy Spirit's Athletic family. At least they come in all sorts of cool colors and styles.

 I took a risk on one shoe that looked kind of cool -- the Naturalizer BZees Mary Jane (right). While they aren't dress shoes or sneakers, they fall into middle ground for me. I'll wear these to work or out on the weekend. I've learned that comfort comes before style at this point. It's really not a choice.

 One of the brands that up until this about a year ago that I could reliably trust were Jambus and J-41s. I wore one pair last week and boy did I pay for it. They seemed comfy enough -- they have memory foam insoles -- but the next day my left knee and hip hurt so bad that I was limping for two days. I had to fall back on my trusty Easy Spirit Mary Janes to get enough support and shock absorption. I was crestfallen. I love those J-41s. I wanted to make a bargain with myself that I can still wear them in some limited way...oy.


 http://www.pamspaulding.net/2013/06/when-you-have-neuropathy-damaged-feet.html

Verging On Obese Get Ready For Neuropathy!

Today's post from mdedge.com (see link below) is so short, you might wonder why it appears here at all. It may be short but at the end of a festive season for many (if only it were festive for all!) where vast quantities of food have been eaten and waistlines have been irreversibly expanded, you may want to spare a thought for the potential consequences. Have you seen the latest statistics about obesity in the population!!! Of course, over eating and regularly eating the 'wrong' sort of food can lead to diabetes and the commonest cause of neuropathy is diabetes but the message here is much wider than that. This study shows that obese people are prone to nerve damage, irrespective of their glucose and blood sugar levels, so the message is clear - obesity is to be avoided at all costs, for all sorts of health reasons. Unfortunately, neuropathy doesn't frighten people until they have it and then it's too late! We've not even reached New Year's Eve yet, after a crazy year in human history, so before you go on that last food binge before 2017 (it's never the 'last' one), try to make and stick to a New Year's resolution before it sticks to your waistline and brings you nerve damage which you'll regret for ever!
 

Causes of Polyneuropathy in an Obese Population
JAMA Neurol; ePub 2016 Oct 31; Callaghan, et al November 15, 2016

The prevalence of polyneuropathy is high in obese individuals, even those with normal glucose levels, with diabetes, prediabetes, and obesity being the likely metabolic drivers, a recent study found. This cross-sectional study included 102 obese participants (mean age 52.9 years; 45 [44.1%] with normoglycemia, 31 [30.4%] with prediabetes, and 26 [25.5%] with type 2 diabetes), and 53 lean controls. 

Researchers found:
The prevalence of polyneuropathy was 3.8% in lean controls (n=2), 11.1% in the obese participants with normoglycemia (n=5), 29% in the obese participants with prediabetes (n=9), and 34.6% in obese participants with diabetes (n=9). 

Age (OR, 1.09), diabetes (OR, 4.90), and waist circumferences (OR, 1.24) were significantly associated with neuropathy in multivariable models. 

Prediabetes (OR, 3.82) was not significantly associated with neuropathy.

Citation: Callaghan BC, Xia R, Reynolds E, et al. Association between metabolic syndrome components and polyneuropathy in an obese population. [Published online ahead of print October 31, 2016]. JAMA Neurol. doi:10.1001/jamaneurol.2016.3745.

Commentary: Polyneuropathy can range in severity from bothersome, with intermittent tingling and numbness, to severe and disabling. We are familiar with it as a long-term complication of diabetes as well as occurring sporadically in patients without diabetes. We are beginning to recognize that many of the sporadic cases in patients without diabetes may be due to prediabetes and obesity. A previous paper in Diabetes Care demonstrated that evidence of polyneuropathy was found in 49% of a large cohort of patients with prediabetes and that progression of glucose intolerance over 3 years predicted a higher risk of peripheral neuropathy and nerve dysfunction.1 The lack of relationship to prediabetes reported in the current paper is likely due to the relatively small numbers of patients with prediabetes in the study, since the hazard ratio for polyneuropathy with prediabetes was 3.8. The current paper expands these non-diabetes related risk factors for peripheral neuropathy to include obesity as well as diabetes. —Neil Skolnik, MD
Lee CC, et al. Peripheral neuropathy and nerve dysfunction in individuals at high risk for type 2 diabetes: The PROMISE cohort. Diabetes Care. 2015;38:1-8. doi:10.2337/dc14-2585.

http://www.mdedge.com/jfponline/clinical-edge/summary/diabetes/causes-polyneuropathy-obese-population

Milnacipran Savella An Option For Neuropathic Pain

Today's post from prohealth.com (see link below) looks at the effectiveness of Milnacipran (brand names Savella, Ixel) in treating pain stemming from various neuropathic conditions; in this case concentrating on fibromyalgia but including peripheral neuropathy in most of its forms. You may not have heard of Savella because it's certainly not as widely prescribed as other serotonin–norepinephrine reuptake inhibitors (SNRI) like Duloxetine (Cymbalta) but from reading this article and appraisal, it certainly seems to be a viable alternative. This is especially true if you consider that they claim that there are far fewer mood disorders as side effects and as many patients on other anti-depressants will testify; that's a mighty big plus. This thorough article looks at the reasons why these medications are prescribed for nerve pain and the story of Savella itself. It's interesting to see how getting the process of approval from the American FDA works. As with any neuropathy treatment however; what works for some doesn't work for others, therefore these drugs should always be regarded as being alternatives for each other and if one group doesn't work for you, you move on to something else.

Fibromyalgia – The Savella Story
By Cort Johnson • www.ProHealth.com • September 7, 2015

Milnacipran (brand names: Savella, Ixel) is the third and last drug the FDA approved for the treatment of fibromyalgia in the United States. The fourth serotonin–norepinephrine reuptake inhibitor (SNRI), to be introduced in the U.S., Savella stops the reuptake of serotonin and norepinephrine in the nerves synapses – making more of those neurotransmitters available to the central nervous system. Savella is the most “balanced” SNRI in that it increases serotonin and norepinephrine equally. Unlike other SNRI’s it does not affect dopamine levels.

SNRI’s are usually considered antidepressants (although they are also often used to treat anxiety, obsessive compulsive disorder and ADHD) but two SNRI’s, Savella and Cymbalta (Duloexetine) have also been shown to be effective in treating chronic pain in some patients without mood disorders.

Several kinds of antidepressants (including TCA’s), in fact, are now commonly used to treat many kinds of pain including arthritis, central pain syndrome, fibromyalgia, low back pain, migraines, nerve damage from diabetes (diabetic neuropathy), and nerve damage from shingles (postherpetic neuralgia). Lower doses than used in depression are usually sufficient.

Pain Modulation

Different nerve pathways in the central nervous system can promote or inhibit pain. Reduced activity of the pain inhibition circuits appears to be the major problem in FM. The pain reducing circuits originating in the brainstem are loaded with neurons that respond to serotonin and norepinephrine. By increasing serotonin or norepinephrine levels, antidepressants may be reinvigorating the pain inhibiting circuits in the brainstem – thus lowering pain levels.

Antidepressants may also block receptors (histamine, NMDA, a-adrenergic) involved in pain processing, effect ion channel activity, (weakly) stimulate opioid receptors and may even affect immune regulation. Some recent animal model evidence suggests that Savella and similar drugs may enhance the effectiveness of microglial inhibitors such as minocycline.

It’s possible, even likely, that nerve pain and depression have an overlapping pathophysiology. Similar neurotransmitters, HPA axis, autonomic nervous system and immune alterations can be found in each.

The Savella Fibromyalgia Story

Savella has been the least of the big three drugs for FM. Cymbalta has been FDA approved for six conditions in the U.S., Lyrica for four and Savella for only one. Cymbalta is expected to challenge Lyrica for the top FM drug in sales, with Savella far, far behind.

Savella’s approval record is rather mixed, as well. Savella is FDA approved for treating fibromyalgia but not depression. Rather confusingly, it is not approved for fibromyalgia in Europe but is widely used for depression. It is approved for treating FM in Australia.

One of the advantages of getting FDA approval for a drug is that the drug tends to get more study. Since 2009, Savella has sparked numerous studies, with increasing studies in the last couple of years.

A 2010 review indicated that Savella can be effective in managing pain and improving fatigue and cognitive dysfunction as well as depression.

Side effects were limiting, however, with almost 25% of patients dropping out of clinical trials because of them. (Twelve percent of patients taking the placebo dropped out.)

One milnacipran review noted that most side effects vanish after a week or two and that slowly uptitrating the drug helps. The doctors recommended starting with 12.5 mg once daily in the morning for one week, then increasing to 25 mg once daily in the morning for 2 weeks, and then 50 mg once daily in the morning. In some patients they may add a evening dose.

Because milnacipran is the only FDA approved FM treatment shown to improve symptoms of fatigue and cognitive dysfunction in phase 3 clinical trials, they recommended using it in patients with brain-fog problems. They also noted that “many patients who have previously failed to respond to either of the other two indicated medications can have an excellent therapeutic response to milnacipran.”

A 2012 Cochrane Review, however, was not quite as enthusiastic. It stated that the drug does provide moderate pain relief (30% reduction) in about 40% of patients, but that placebo provided about a similar reduction to about 30% of patients. (The placebo response rate in chronic pain tends to be high. A later analysis found that almost 20% of FM patients on placebo in 18 studies experienced a 50% in reduction in pain.) In contrast to placebo, though, studies indicate that milnacipran (or Savella or Ibex) does appear to maintain its effectiveness long term.

A 2012 study found that the presence or absence of depression had little effect on milnacipran’s effectiveness in FM; i.e., the drug was effective or not independent of whether a patient was suffering from depression. Milnacipran was also associated with some weight loss (in a rather overweight FM population) over two years of treatment.

A long term analysis of 3,000 FM patients over 11 years, however, found that the FDA approved drugs for FM provided little extra benefit compared to past treatments (NSAID’s and opioids). Interestingly, as the FDA drugs came on line, opioid use in FM continued to increase; almost 50% of FM patients were using mild to strong opioids (mostly mild) by the end of the study. As the use of tricyclic antidepressants such as amitriptyline dropped (27-15%), the proportion of patients who were using Lyrica or the FDA approved antidepressants by the end of the study rose dramatically (about 40%). The new drugs increased costs for the patients, but study found that the clinical benefits of the new drugs were limited with 2-5% reductions in pain and no increases in functionality.

A large three-year study, however, found that 70% of FM patients on milnacipran reported themselves “much improved” or “very much improved.”

Meanwhile a quite small study found no significant differences in pain reduction or cognitive improvement between milnacipran and placebo. The home of the NIH institute for FM, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) got into the act by funding a CBT/milnacipran study that found “moderate benefits” to combining the two therapies.

Doctors had earlier reported that milnacipran was often effective in some FM patients who didn’t do well on other FM drugs. That report was largely borne out in a 2013 study that found that 33% of patients who did not respond to duloxetine (Cymbalta) were classified as responders to Savella.

By 2013 the drug industry was clearly tiring of meta-analyses finding rather low clinical benefits to their drugs. Researchers associated with major drug companies penned a review suggesting that these analyses “do not always tell the full story” and that some benefits had been missed.

A large 2013 study continued the push-back from the drug industry. A large study lead by an Eli Lily researcher found that patients using FDA approved drugs or tricyclic antidepressants reported “satisfaction with overall treatment and their fibromyalgia medication (46.0% and 42.8%, respectively)”. They also reported “modest improvements” and high rates of medication use.

Attempts to broaden the reach of milnacipran ensued. It proved to be helpful in reducing the frequency of migraine and headache, two common issues in FM, in a 2014 study. A 2014 analysis of three studies found that milnacipran did indeed improve fatigue significantly (30% reduction in fatigue) in about 15-20% of patients. A meta-analysis, however, suggested Savella was no better than placebo at reducing neuropathic pain.

Finally, the first pediatric study of milnacipran in FM had mixed results. The trial – co-authored by Lucinda Bateman – suggested the drug may improve symptoms of FM in kids at about the same rate as it does in adults, but the authors had so much difficulty enrolling pediatric patients that the trial was halted early.

Targeting Patients That Benefit – the Next Step

People with FM have had mixed results on Savella. That’s true for all FDA approved drugs for FM (and probably for all the recommended treatments for it). Lyrica, in particular, has a bad reputation for side effects – including the dreaded weight gain. (For Savella nausea seems to be the biggest problem.)

Realizing they have a PR problem, drug companies are trying to fine-tune who they are giving their drugs to. A recent study “Is the efficacy of Milnacipran predictable?” may be a harbinger of what’s to come. An analysis of three large trials revealed that one subset of FM patient benefited the most from Savella. It found that FM patients with high pain intensity, low anxiety or catastrophizing,
absence of major sleeping problems’ and significant physical limitations in the daily life did best. It suggested that if you have significant levels of anxiety (or catastrophizing), relatively low levels of pain and major sleeping issues you’re probably not going to benefit much from Savella. On the other hand, if you can get your anxiety and sleep under control – you might.

There are no magic bullets for FM but a 30-40% reduction in pain is nothing to sneeze at. People with fibromyalgia trying Savella might want to do two things

Consider whether you fit the above group

if you don’t, take steps to alleviate any of the above factors that might keep you from benefiting from Savella. 
Use the very slow ramp up period suggested by the doctors (see above) 

About the Author: Cort Johnson has had ME/CFS for over 30 years. The founder of Phoenix Rising and Health Rising, Cort has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort's and other bloggers' work at Health Rising.

http://www.prohealth.com/library/showarticle.cfm?libid=21248

Small Foot Wounds A Threat For Neuropathy Sufferers

Today's post from reuters.com (see link below) again addresses diabetics as being the target audience but as so often, this article applies to everyone with neuropathic foot problems, irrespective of the cause. It looks at a Dutch study showing how dangerous small wounds on the feet can be if neglected. This especially applies to neuropathy patients experiencing numbness on their feet. The likelihood is that wounds may go unnoticed and rapidly become ulcerated and infected. It goes on to advise people to pay special attention to footwear and daily foot care, something which may seem obvious but is easily forgotten in the daily struggle to get by.

 

Minor foot wounds a major threat for diabetics
By Krystnell Storr NEW YORK Mon Apr 14, 2014   (Reuters Health) - For people with diabetes, one foot ulcer is very likely to lead to another, according to a new study that finds even minor lesions create a major risk of more severe foot wounds.

The best defense, Dutch researchers say, is to treat even minor sores carefully and to protect feet from pressure and injury with specialized footwear.

"I hope medical specialists, and other health care practitioners will use this knowledge and implement it in clinical practice," said senior author Sicco Bus, staff scientist with the Academic Medical Center at the University of Amsterdam.

People with diabetes often lose feeling in their feet as a result of nerve damage, known as neuropathy. The lack of sensation makes diabetics prone to injure their feet without realizing it, and allows small wounds to grow into serious ulcers that can eventually lead to infection or gangrene.

In the U.S., 26 million Americans have diabetes. Every year, 65,700 of these patients have lower-limb amputations.

Past research has shown that having had a foot ulcer is a significant risk factor for having more of them.

"Ulcer recurrence is a debilitating condition for the patient, risking further complications such as infection and amputation, and influencing loss of patient mobility and quality of life," Bus told Reuters Health.

To find out what factors most strongly predict who will develop foot ulcers, Bus and his colleagues analyzed data from a large trial of specialized footwear for diabetes patients with nerve damage in their feet (see Reuters Health article of January 24, 2013 here: reut.rs/1ewrG4F).

For the new analysis, the researchers focused on 171 participants, all of whom reported having a foot ulcer at least 18 months before the study began. For a period of 18 months, each person was checked for new ulcers every three months, and interviewed about their daily habits.

The pressure on their feet while walking barefoot and in the special footwear was also measured. During one week, sensors in the shoes reported how often the participants wore their shoes and how many steps they took.

During the study period, 71 people developed ulcers on the soles of their feet, 41 of them as a result of unrecognized "trauma," Bus and his colleagues report in the journal Diabetes Care.

Among those 41, the people who had minor lesions when the study began were nine times more likely than those who didn't to develop an ulcer. Often the wounds were in the same place as a previous ulcer, suggesting there was ongoing pressure or injury happening at that spot, according to the researchers.

Patients who wore shoes customized to the pressure points of their feet, however, had a 57 percent lower risk of developing a new ulcer compared to those who didn't.

Currently, to prevent ulcers, doctors and nurses have to check the feet of diabetic patients every day for wounds or use specialized tools for determining pressure points that might be prone to blisters.

"Some diabetics wear wounds on their feet kind of in the same way that a person might wear a hole in their sock, but for a diabetic, this hole gets infected and often leads to an amputated foot," Dr. David Armstrong, a professor of surgery at the University of Arizona, told Reuters Health.

"(Neuropathy) is a massive problem, it's silent, and it doesn't hurt, even in instances of gangrene. It's no one's fault, but no one pays attention to it. This study opens up avenues for prevention," said Armstrong, who was not involved in the research.

The protective effect of customized footwear seen in the study highlights the benefits of personalized healthcare in high-risk patients, noted Dr. Lawrence Lavery, a professor of surgery at the Texas A&M Health Science Center College of Medicine and the Scott and White Memorial Hospital in Temple, Texas.

Private insurers will have to step up to pay the expense, Lavery said. "This is something that is well worth investing in."

SOURCE: bit.ly/1iBJUCL Diabetes Care, online April 4, 2014.

http://www.reuters.com/article/2014/04/14/us-foot-diabetics-idUSBREA3D0UJ20140414

Is Virtual Reality Hypnotherapy A Treatment Option For Neuropathic Pain

Today's post from tandfonline.com (see link below) is a fascinating subject and of possible value for neuropathy patients looking for potential future options regarding their own treatment. It concerns a case study of a patient who has already undergone multiple standard neuropathy treatments without success and contacted one of the authors with a view to trying Virtual Reality Hypnotherapy. Her fascinating story and experiences are shown below and open up the possibility of sophisticated hypnosis being a very useful and possibly standard tool in the treatment of nerve pain in the future. As always, it's assumed cost will be a determining factor.

Virtual Reality Hypnosis In The Treatment Of Chronic Neuropathic Pain: A Case Report 
Brent J. Oneal, David R. Patterson, Maryam Soltani, Aubriana Teeley, and Mark P. Jensen1,2 Volume 56, Issue 4, 2008

The publisher's final edited version of this article is available at Int J Clin Exp Hypn

See other articles in PMC that cite the published article.

Abstract

This case report evaluates virtual reality hypnosis (VRH) in treating chronic neuropathic pain in a patient with a 5-year history of failed treatments. The patient participated in a 6-month trial of VRH, and her pain ratings of intensity and unpleasantness dropped on average 36% and 33%, respectively, over the course of 33 sessions. In addition, she reported both no pain and a reduction of pain for an average of 3.86 and 12.21 hours, respectively, after treatment sessions throughout the course of the VRH treatment. These reductions and the duration of treatment effects following VRH treatment were superior to those following a trial of standard hypnosis (non-VR) treatment. However, the pain reductions with VRH did not persist over long periods of time. The findings support the potential of VRH treatment for helping individuals with refractory chronic pain conditions.

Hypnotic analgesia has become an increasingly important aspect in the treatment of clinical and experimental pain (Lang et al., 2000; Montgomery, DuHamel; Redd, 2000) and has been used on virtually every type of pain (Patterson; Jensen, 2003). Patterson and Jensen reviewed 29 randomized, controlled studies of hypnotic analgesia and concluded that (a) the evidence supporting the efficacy of hypnotic analgesia is strong, and (b) hypnotizability is usually related to outcome in studies that measure this variable. With respect to the importance of hypnotizability, one potential strategy for increasing the impact of hypnosis is to make hypnotic induction less effortful. We hypothesized that by providing visual stimuli for a patient during hypnosis treatment and giving the patient an illusion of “sinking into a virtual world,” the induction would require less concentration and mental effort from the patient and therefore might be more effective than standard hypnosis. As Patterson, Tininenko, Schmidt, and Sharar (2004) posited, using computer-generated stimuli to capture and to guide the patient's attention may not only make the induction less effortful but also more widely available, given that such a treatment would not require the presence of a clinician trained in hypnosis.

Although there have been few attempts to apply computer-generated hypnosis to clinical situations, results from a recent study on procedural pain revealed that hypnosis delivered through immersive virtual reality (VR) was very effective in reducing patients' reported pain and anxiety and may have reduced the need for opioid analgesics (Patterson, Wiechman, Jensen, Sharar, 2006). Immersive VR hypnosis (VRH) isolates patients from the outside world. With VR, patients have the illusion of going inside the three-dimensional computer-generated environment. Because VR is designed to be a highly attention-grabbing experience, it reduces the amount of attention available to process pain and instead maximizes the person's ability to narrowly focus on a hypnotic induction thereby facilitating dissociation of pain. The goal of creating VRH was to develop a three-dimensional, immersive virtual reality technology that could guide the patient through the same steps that are used when hypnosis is induced through an interpersonal process.

While there is a recent interest in using VR as a medium for hypnosis, this application is relatively new and has primarily been applied to acute procedural pain. The purpose of this case study was to expand the use of VRH to the treatment of a patient with chronic neuropathic pain, and, to our knowledge, it is the first research of its kind. In addition, in the present study, we were able to compare the results of the current trial of VRH to the results of a previous trial of standard hypnosis (non-VR) treatment that was conducted with the patient a few years earlier by one of the investigators. We hypothesized that this patient would have a significant reduction in pain and achieve a greater and longer lasting reduction in pain with VRH than standard (non-VR) hypnosis.

Case History

The patient was a 36-year-old female with a 5-year history of C4 tetraplegia and upper extremity neuropathic pain. She had no psychiatric history and was otherwise healthy. Approximately 5 years prior to the initiation of VRH treatment, she was injured as the passenger in a motor vehicle crash and spent close to 4 months in a major regional trauma center. Since that time, she has participated in both inpatient and outpatient rehabilitation and has worked closely with medical staff through a major regional multidisciplinary pain clinic. She described her pain as a constant burning sensation along the lateral aspects of her shoulders, medial arms, and proximal/anterior forearms, which was worse in her left arm. She was unable to wear clothes with sleeves as those garments increased her pain. She was also unable to be outdoors when there was any wind or precipitation due to her pain. In addition, her pain was very sensitive to temperature, and if the temperature was more than a few degrees above or below 73° F, her pain intensified. Finally, she also reported significant sleep difficulties secondary to her pain.

She has tried many treatments for pain management over the years, including multiple medications, physical therapy, massage therapy, acupuncture, Tibetan sound therapy, meditation, and electrical stimulation. Also, as noted above, she participated in a clinical trial of standard (non-VR) self-hypnosis training (Jensen et al., 2005, 2008). She reported that all of those treatments had been relatively unhelpful in the reduction of her pain.

Regarding past medications, this patient has tried over 15 medications to help her with pain management, including oxycodone, methadone, oxcarbazepine (Trileptal), venlafaxine (Effexor), diazepam (Valium), lorazepam (Ativan), pregabalin, mexiletine, and triazolam. She used to meet with her physician through the multidisciplinary pain clinic once every 3 weeks for pain management. However, for the year prior to the time that this study began, she had been meeting with that professional about once every 2 months.

During this study, the patient was taking the following medications: Diazepam 5 mg SID for sleep and pain; oxcarbazepine 300 mg SID for pain; trazodone 100–150 mg SID for sleep; mexiletine 150 mg BID for pain; venlafaxine 150 mg in am/75 mg in pm for pain; and tolterodine (Detrol LA) 4 mg SID for treatment of an overactive bladder.

Procedure

The patient became known to us after she contacted one of the authors with an interest in virtual reality distraction after hearing about this in the media. She was told that virtual reality distraction is not well suited for chronic pain but also that we could provide virtual reality hypnosis to see if this might be of benefit for her. The first two authors met with the patient to explain the study and VRH treatment. She consented to participate. The measures and data collection procedures for this study were very similar to those used in a previous trial of standard hypnosis (Jensen et al., 2005). Baseline and follow-up data was obtained from the patient by telephone interview. In order to determine the longer-term effects of having participated in VRH, the patient was asked to take a hiatus from treatment for a 1-month period. During that time one of the authors contacted her on a weekly basis by telephone to assess her comfort with the treatment hiatus and she was told that at any time during the break, if her pain became too intense, she was welcome to return to VRH sooner than the 1-month timeframe. Session logs were completed with the patient before and after each VRH session. The treatment outcome measures analyzed for this case report included average pain intensity and pain unpleasantness, as well as amount of time (in hours) the patient experienced a reduction or absence of pain between treatment sessions. The patient was also administered the Stanford Hypnotic Clinical Scale (SHCS; Morgan; Hilgard, 1978–1979) in order to assess level of hypnotizability.

The patient participated in a total of 33 VRH treatment sessions over the course of 6-months. All sessions occurred in a private office at a regional trauma medical center in Seattle, Washington. All sessions involved the patient receiving an audio recording of a hypnotic induction, suggestions for pain relief, and then alerting while drifting through a three-dimensional computer-generated virtual world called SnowWorld (See Patterson, Tininenko, Schmidt, Sharar, 2004; Patterson et al., 2006 for details of SnowWorld). Between sessions, the patient was encouraged to practice self-hypnosis regularly by using the compact disc that was given to her with the audio of the VRH protocol. In other words, she could listen to the audio version of the hypnosis at home, but did not have the visual stimuli available during the at-home practice sessions. She was also asked to complete daily diaries of her pain, unpleasantness, and frequency of home practice throughout the 6-months of treatment. She e-mailed the diaries to the first author of this article.

The VRH program began by having the patient hovering at the top of the snow canyon while an audiotape of the hypnotist's voice prepared the patient for what she would experience during the virtual hypnosis. After approximately 6 minutes of instruction, she began a 6-minute descent in the “snowy” 3-D canyon and she experienced herself as floating by numbers (1 through 10, in order) and was instructed to deepen her relaxation as she passed by each number. At number 10, she was told that she was in her most relaxed state and had descended deep into the canyon. At that point, she experienced herself hovering above the lake and was given about 18 minutes of audio posthypnotic suggestions. That was followed by approximately 10 minutes of alerting as she ascended back up the “snowy” 3-D canyon and floated by numbers (10 through 1, in order).

The Nature of Hypnotic Suggestions

Although the exact transcript of the hypnotic suggestions is too long to report, we will provide examples of the content. First, there was an introduction to the lake. The lake was described to the patient, and she was encouraged to become increasingly absorbed in the scene and to let her body relax. Then the program addressed her mind and how it could be a tremendous resource to help her feel safe and comfortable. The next section discussed how pain affects her life. An example of this dialogue is, “Part of you knows what it takes to feel more comfortable, to allow you to heal faster. It is there, it's just that it only comes to you, to your awareness, during certain times of your life, and what you realize is that this part of your mind is going to become present in your life during this time of healing, or during the time when you are undergoing pain.” The following segment dealt with asking the patient to imagine a time before the trauma. She was then instructed to recall images from a time in the past when she had positive experiences and to remember how comfortable she felt then.

After she was asked to recall positive images and experiences from her past, she was directed to move forward in time and to continue to see positive images of herself functioning well. She was told that images from the past and from the future should start to have a strong connection. Then the patient was given suggestions for sleeping better through the night, and it was also suggested that any exercises she engages in would become easier. It was recommended that she change the experience of her pain to a sense of coolness or numbness, or even forget about it altogether. She was also guided that as her pain improved she would find the ability to continue doing things that make her feel better, such as increasing her movement and participating more in life. The lake segment concluded by giving the patient a chance to engage in any other experiences or images that she might like to have, or to give herself positive suggestions of her own. She was then provided a period of silence for her to do that. The final suggestion focused on the fact that her comfort would be far greater when she took off the VR helmet than it was before she started the session.

Outcome Measures

The outcome measures analyzed for this study included pre- to posttreatment through 1-month follow-up of average pain intensity and pain unpleasantness. These outcome measures were the two that demonstrated significant effects in the original hypnosis only (non-VR) study that this patient previously participated in (Jensen et al., 2005). Both outcome domains were assessed at each outcome assessment point by contacting the patient four times within a 7-day window, and asking her to rate her usual pain intensity and pain unpleasantness over the past 24 hours on 0 (no pain; not bad at all) to 10 (the most intense pain sensation imaginable; the most intense bad feeling possible for me) Numerical Rating Scales. The four ratings for each outcome domain were then combined into composite measures of average pain intensity and pain unpleasantness.

In addition, the patient rated pain intensity and unpleasantness before and after each VRH session, using the same 0 to 10 Numerical Rating Scales described. These ratings were averaged into separate composite scores. That is, the pre- and postsession pain intensity and pain unpleasantness ratings were averaged for both the first 10 sessions and also all 33 sessions of VRH. Developing the composite scores from the first 10 sessions of VRH allowed for a direct comparison between VRH and the standard (non-VR) hypnosis trial, which included 10 sessions of treatment. The final outcome measure was the amount of time (in hours) that the patient experienced a reduction or absence of pain between treatment sessions. In the same manner as described above, these ratings were averaged into separate composite scores (VRH-33 sessions, VRH-first 10 sessions, standard hypnosis-10 sessions).

Outcome Data

Relative to the pretreatment baseline, the patient's ratings of average pain intensity and pain unpleasantness were not significantly different from her posttreatment or 1-month follow-up ratings. This outcome was similar for both the current VRH study as well as the hypnosis (non-VR) study that was conducted in 2004–2005. See Table 1 for the patient's average pain intensity and pain unpleasantness ratings pre/posttreatment as well as at 1-month follow-up for both the VRH and hypnosis (non-VR) treatments. In other words, VRH did not create lasting changes in the patient's pain perception.



Table 1


Means and SDs of Average Intensity of Pain and Pain Unpleasantness at Pretreatment, Posttreatment, and 1-Month Fallow-Up for VRH and Hypnosis Treatments

However, when investigating pain levels immediately after treatment, the patient's average pain intensity levels and pain unpleasantness ratings from pre- to posttreatment session, there was a 36% reduction in her average pain intensity and a 33% reduction in her average pain unpleasantness from pre- to post-VRH (see Table 2). As explained above, in order to directly compare the VRH and hypnosis (non-VR) ratings, the first 10 sessions of the VRH treatment were compared to the 10 sessions of hypnosis (non-VR) treatment that this patient had previously completed. See Table 2 for a depiction of the VRH 10-session and the hypnosis (non-VR) 10-session ratings. This patient reported an average of 25% pain intensity reduction and 20% pain unpleasantness reduction over the course of the first 10 sessions of VRH, compared to an average of 7% pain intensity reduction and 15% pain unpleasantness reduction over the course of the 10-session hypnosis (non-VR) treatment.



Table 2

Means and SDs of Presession to Postsession Intensity of Pain and Unpleasantness of Pain for 33-Sessions of Virtual Reality Hypnosis (VRH33), 10-Sessions of Virtual Reality Hypnosis (VRH10), and 10-Sessions of Hypnosis (Hyp10)

With respect to the duration of pain decrease between treatment sessions, this patient reported an average of 12.21 hours of pain reduction and 3.86 hours of being pain free over the course of the 33 sessions of VRH treatment. For the first 10 sessions of the VRH treatment she reported an average of 8.5 hours of pain reduction and 4.3 hours of being pain free, compared to an average of 1 hour of pain reduction and 0 hours of being pain free over the course of the 10-session hypnosis (non-VR) treatment (See Table 3).




Table 3

Means and SDs of the Duration (in Hours) of No Pain and Reduced Pain Throughout the Course of 33-Sessions of Virtual Reality Hypnosis (VRH33), 10-Sessions of Virtual Reality Hypnosis (VRH10), and 10-Sessions of Hypnosis (Hyp10)

Finally, on the Stanford Hypnotic Clinical Scale (Morgan; Hilgard, 1978–1979), the patient received a score of 2, placing her in the low to low-moderate range of hypnotizability.

Discussion
 
This report represents our first attempt to apply immersive virtual reality hypnosis to treat chronic neuropathic pain in a woman with a spinal cord injury who had not responded to any form of prior treatment. The patient's subjective ratings of pain intensity and pain unpleasantness showed an immediate reduction that averaged 36% and 33%, respectively, from pre- to post-VRH treatment. In addition, the amount of time that this patient experienced no pain or a reduction of pain over the course of the 33 VRH-treatment sessions averaged 3.86 and 12.21 hours, respectively. Furthermore, when compared to hypnosis alone (non-VR), this patient experienced a greater reduction in pain intensity and pain unpleasantness as well as longer lasting freedom from pain throughout the course of treatment with VRH.

The fact that this patient's pretreatment ratings of pain intensity and pain unpleasantness were not significantly different from her posttreatment and 1-month follow-up ratings of pain intensity and pain unpleasantness suggests that VRH treatment was helpful for her on a time-limited basis, that is, on average, 12.1 hours. The relatively short-lived effect of VRH in this patient's case is consistent with recent research suggesting that although hypnosis may not “cure” a person's chronic pain, it can be an important part of a person's plan to manage chronic pain on a daily basis (Jensen et al., 2008). In other words, hypnosis can provide many patients with a means of coping with pain, much like they might use medications (that also provide only short-term relief), but without the negative side-effects of those medications. In fact, research suggests that hypnosis can provide many beneficial “side effects” (e.g., improved well-being, improved sense of control over pain, improved sleep, etc.) that can contribute to a patient's quality of life over and above its effects on pain (Jensen et al., 2006).

Thus, even though some patients (about between 20%–30%, cf. Jensen et al., 2008) with chronic pain can experience substantial and long-term reductions in average daily pain following hypnosis treatment, many more patients than this report some relief of pain via hypnosis, view it as helpful and continue to use it up to 12 months following treatment. Therefore, although the patient in this case report was not “cured” of her pain, which would have been surprising given the refractory nature of it, she did achieve meaningful benefits through the use of VRH that lasted for many hours. Furthermore, while overall pain measurements did not change substantially, observation of means suggests that the directions of changes were in the direction anticipated. Specifically, overall ratings went down during the treatment period rather than baseline and then increased again during the month with no treatment.

The findings that this patient, who has suffered from severe and chronic neuropathic pain for over 5 years and has tried a myriad of other interventions, including over 15 medication trials, achieved a significant and lasting reduction in her pain throughout the course of VRH treatment is extremely promising. It was interesting that the patient went through the efforts to come to the hospital for months; given her spinal cord injury this was logistically difficult for her. It was also noteworthy that she reported that she benefited more from the induction when it was paired to the visual stimuli, rather than presented simply through audiotape. She also chose to resume treatment after a 1-month no-treatment period requested by the investigators. During one of the final VRH sessions before the treatment hiatus, this patient indicated that over time she was learning how to control her pain better, largely due to the experience that she has received through virtual reality hypnosis.

It was also noteworthy that the patient scored low on a scale measuring hypnotizability. Although the Stanford Hypnotic Clinical Scale is a screening measure, it has been reported to have good correlations with the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C; Bryant, Guthrie, Moulds, Nixon, and; Felmingham, 2003). The fact that the patient had a good response to the virtual reality hypnosis with a relatively low hypnotizability score is encouraging to us. Our hope is that this technology will be most useful to patients that do not have a high level of hypnotizability. Specifically, it may be that providing attention-grabbing stimuli that matches the suggestions may help patients become more absorbed in the process when this does not come naturally.

We maintain that this patient's chronic neuropathic pain is a challenging clinical problem with no easy solution. This report is provided after 6-months of treatment, with an empirical hiatus of no treatment. Our hope is that with repeated treatment, the pain relief experienced by the patient will last for greater, and hopefully more extensive, periods of time.

There are several limitations to this case report. As with a study of this design, we are not controlling for historical factors that might have influenced the patient's pain perception; randomized controlled studies are necessary to control such extraneous variables. One of the biggest threats to validity is not knowing if the patient reported pain reductions simply to please the investigators. However, we should note that she was willing to report no reductions in pain over several periods during the study. Further, although historical confounds are always a consideration, it is difficult to argue that the drops in pain that occurred over almost all of the 33 treatments were attributable to anything other than the intervention. The activity required to travel to the hospital was more likely to exacerbate than to reduce pain in itself. Finally, this technology used in the intervention was novel and has not yet been refined for use. In spite of these drawbacks, however, we view the pain reductions that occurred with VRH, especially in light of previous poor response to other treatments, as promising and indicate that additional investigation of virtual reality hypnosis for chronic pain is warranted.

Footnotes

1This article was supported by grants from the National Institutes of Health (R01 GM42725-09A1 and R01AR054115-01A1) as well as with gifts or grants from the Paul Allen Foundation, Scan Design by Inger and Jens Bruun Foundation, Gustavus and Louise Pffiefer Research Foundation, and other private donors. The software expertise necessary to design the immersive virtual reality delivery system was provided by Hunter Hoffman, Ph.D., at the University of Washington Human Interface Technology Lab as well as Ari Hollander at Imprintit.com.

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http://www.tandfonline.com/doi/abs/10.1080/00207140802255534?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed#.U5_rnbFqQUM

Stem Cell Injections For Nerve Pain

Today's post from eurekalert.org (see link below) could potentially be as important an announcement as any other so-called neuropathy breakthroughs of the last few years. if only it were as simple as the title suggests. One of the major causes of nerve pain is the disintegration or degeneration of the myelin protective sheath around nerves. As with electrical wiring, if the insulation material is damaged (in this case, myelin), the live wire is exposed, causing short-outs etc. Finding something that can repair myelin at the point of damage, would be a major discovery in the fight against neuropathic pain and other symptoms. This article suggests that they may have found exactly that and by simply injecting certain cells extracted from bone marrow, the myelin sheath can be restored, thus blocking off the cause of pain. Whoopee! However, now come the disclaimers! As always with this sort of news, we discover that the research is only at the lab animal testing stage and that this particular form of stem cell therapy is closer to theory than practical application. This means that once more hopes are raised but the reality is that we're still years away from practical treatments. Okay, we'd rather hear about good news in the research field than be kept in the dark but there should always be a subtitle in heavy print, warning the neuropathy patient that they shouldn't start planning to restore their full and busy lives just yet. It's the nature of the beast!
 

Stem cell injections improve diabetic neuropathy in animal models 
Public Release: 23-Jun-2015 Putnam Valley, NY. (June 23, 2015)

 Bone-marrow-derived mesenchymal cells promote blood vessel growth and re-myelination of peripheral nerves
 
Cell Transplantation Center of Excellence for Aging and Brain Repair

 - Diabetic neuropathy (DN) is a condition in which perpetually high blood sugar causes nerve damage, resulting in a myriad of symptoms such as numbness, reduced ability to detect painful stimuli, muscle weakness, pain, and muscle spasms. DN affects up to 60 percent of patients with diabetes, is often the cause of foot ulcers, and can ultimately result in amputations. There is no curative therapy for DN, but a recent study carried out by a team of researchers in the U.S. and Korea has found that laboratory animals modeled with DN can experience both angiogenesis (blood vessel growth) and nerve re-myelination following injections of mesenchymal stem cells derived from bone marrow (BM-MSCs).

Their study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1386_Han_et_al

The researchers used mesenchymal stem cells, which can be easily isolated from a variety of sources, such as adipose (fat) tissues, tendons, peripheral blood, umbilical cord blood, and bone marrow. MSCs derived from bone marrow (BM-MSCs) have been among the most successfully transplanted cells, offering therapeutic benefits for a wide range of conditions, from serious burns to cardiovascular diseases, including heart attack and stroke.

In this study, laboratory rats modeled with diabetes were randomly assigned to BM-MSC or saline injection groups 12 weeks after the induction of diabetes. The non-diabetic control group of rats was age- and sex-matched. DN was confirmed by latency in nerve conduction velocity tests.

"We investigated whether local transplantation of BM-MSCs could attenuate or reverse experimental DN by modulating angiogenesis and restoring myelin, the electrically insulating substance surrounding nerves that is reduced by DN," said study co-author Dr. Young-sup Yoon, Professor at the Department of Medicine, Division of Cardiology at Emory University School of Medicine. "In this study we have provided the first evidence that intramuscular injected BM-MSCs migrate to nerves and can play a therapeutic role."

According to the researchers, their findings indicate that intramuscular injection of MSCs resulted in an increase of multiple angiogenic and neurotrophic factors associated with blood vessel growth and subsequently aided the survival of diabetic nerves, suggesting that BM-MSC transplantation restored both the myelin sheath and nerve cells in diabetic sciatic nerves.

"We identified several new mechanisms by which MSCs can improve DN," said the researchers. "First, we demonstrated that numerous engraftments migrated to and survived in the diabetic nerves. Second, we demonstrated a robust increase in vascularity. Third, we found the first evidence that MSCs can directly modulate re-myelination and axonal regeneration."

The researchers concluded that DN, for which there is no other therapeutic option, can be an "initial target for cell therapy" and that transplantation of BM- MSCs "represents a novel therapeutic option for treating DN."

"Currently, the only treatment options available for DN are palliative (focused on alleviating pain) in nature, or are directed at slowing the progression of the disease by tightly controlling blood sugar levels, "says Dr. John R. Sladek, Jr., Professor of Neurology, Pediatrics, and Neuroscience, Department of Neurology at the University of Colorado School of Medicine. "This study offers new insight into the benefits of cell therapy as a possible treatment option for a disease that significantly diminishes quality of life for diabetic patients. Safety and efficacy for human application must be evaluated to further determine the feasibility of BM-MSC transplantation for treatment of DN."

Contact: Dr. Young-sup Yoon, Professor of Medicine, Department of Medicine, Division of Cardiology, Emory University School of Medicine, 101 Woodruff Circle, WMB 3009, Atlanta, GA 30322, USA.
Phone: 404-727-8176
Email: yyoon5@emory.edu
Fax: 404-727-3988

Citation: Han, J. W.; Choi, D.; Lee, M. Y.; Huh, Y. H.; Yoon, Y-S. Bone marrow-derived mesenchymal stem cells improve diabetic neuropathy by direct modulation of both angiogenesis and myelination in peripheral nerves. Cell Transplant. Appeared or available on-line: May 13, 2015.

The Coeditors-in-chief for CELL TRANSPLANTATION are at the Diabetes Research Institute, University of Miami Miller School of Medicine and Center for Neuropsychiatry, China Medical University Hospital, TaiChung, Taiwan. Contact, Camillo Ricordi, MD at ricordi@miami.edu or Shinn-Zong Lin, MD, PhD at shinnzong@yahoo.com.tw or David Eve, PhD or Samantha Portis, MS, at celltransplantation@gmail.com

News release by Florida Science Communications http://www.sciencescribe.net

http://www.eurekalert.org/pub_releases/2015-06/ctco-sci062315.php

Problems With Legalising Marijuana For Neuropathy Pain

Today's post from inforum.com (see link below) is really a local news story but is symptomatic of the arguments surrounding marijuana as a medical drug. Rational argument and scientific evidence seems to strongly suggest that marijuana is one of the most effective pain medications for people living with severe neuropathy, yet outdated laws both local and national stand firmly in the way. Sometimes the punishments for possession are so severe that people are discouraged from using something that will relieve their pain. Slowly but surely, official attitudes are changing but it's a slow and painful process as this story from North Dakota illustrates.

Backers fire up attempt to get medical marijuana legalized in ND
By Helmut Schmidt on Jan 21, 2015 .

FARGO – If you ask Rilie Morgan, it’s time for North Dakota to make medical marijuana legal.

The affable silver-haired financial planner, who goes by his middle name, Ray, has neuropathy.

The neurological affliction has for the past two years given the 64-year-old Fargo man constant tingling in his feet and calves, sometimes punctuated by sharp shooting pains.

“It’s like when your hand or foot falls asleep and you get a tingling sensation. It’s constant. It’s 24/7,” Morgan said.

“If your mind is busy, then it’s not too bad. But once in a while there is some pain, a shooting pain that’s like, ‘Wow! Where did that come from?’ ” he said. “You always know it’s there.”

Morgan, a partner in a Fargo financial firm, said a painkiller he uses can cause liver damage. He used morphine for several months after a back surgery. That’s a route he doesn’t want to take again.

He said medical cannabis may make the pain “a little more tolerable. I’d like to explore the possibility anyway.”

State Rep. Pamela Anderson, a Fargo Democrat, has taken up Morgan’s cause, and introduced House Bill 1430 on Monday.

The bill would allow patients and caregivers to possess up to 2½ ounces of cannabis – or products such as cannabis oils, beverages, vapors, extracts, ointments or pills – for medical use.

It also has a provision that allows people who have obtained a prescription for medical marijuana to cultivate up to six marijuana plants.

The bill lists a number of ills eligible for treatment: cancer, glaucoma, HIV, hepatitis C, amyotrophic lateral sclerosis (Lou Gehrig’s disease), Crohn’s disease, ulcerative colitis, agitation due to Alzheimer’s disease and post-traumatic stress disorder.

Conditions that lead to wasting, severe debilitating pain or nausea, seizures, or severe and persistent muscle spasms, including those characteristic of multiple sclerosis are also listed, with an option for more to be added.

HB 1430 was crafted from information on what other states have done to regulate medical marijuana that was provided by the Council for State Governments, Anderson said.

She said she’s heard from people suffering from glaucoma, multiple sclerosis or seizures who would support legalizing medical cannabis in North Dakota.

To date, 23 states and the District of Columbia allow the use of medical cannabis, including neighboring Minnesota and Montana.

Rep. Kathy Hawken, R-Fargo, a co-sponsor of the bill, has her own connection to the issue – a son who suffers from seizures.

“More than one neurologist has said that if he could, he would prescribe medical marijuana,” Hawken said. “They think it does work.”

She said the bill contains controls on medical marijuana products from farm to pharmacy.

But she’s unsure of its fate – at least this year.

“I think it is something that will eventually pass. This session? Well, stranger things have happened,” Hawken said. “Realistically, at least the discussion will start.”

The 29-page bill provides for:
Exemptions from prosecution for the possession, manufacture or sale of medical marijuana for those licensed, and for people certified as in need of medical marijuana by a physician.
Creating a system to license manufacturing and distribution of medical marijuana products.
Criminal penalties for violating provisions of the medical marijuana law.
Protections from discrimination in schooling and housing for medical cannabis users, unless allowing the use would violate federal law or regulations.

Rep. Eliot Glassheim, D-Grand Forks, another bill sponsor, said he used to smoke a joint now and then 30 years ago.

“It seems to me the whole hysteria was misplaced,” Glassheim said.

Now, he’s being treated for cancer.

“It’s not in remission, but it’s not spreading. I feel OK,” he said. He understands that others dealing with the side effects of cancer treatments could benefit from having medical marijuana available as an option.

“I certainly could imagine a situation where you’re nauseous or where you’re in unbearable pain,” Glassheim said.

Supporting the bill, “just seemed to me to be a rational thing to do,” he said.

Glassheim expects some resistance.

“It may have to wait until next session. I expect it will pass one of these days,” he said. “It’s one of these bills people have to get their minds around.”

Morgan, meanwhile, is plan a trip to Arizona to test-drive the idea of becoming a snowbird as he nears retirement. Arizona also allows medical cannabis to treat a number of ailments, he said.

But he will hop on a plane to Bismarck to testify for HB 1430, he said.

“I think medical marijuana has been understudied” for its efficacy, Morgan said. “I think it’s time to explore the options and let pharmaceutical companies see what they can come up with. It’s time.”

Other sponsors of HB 1430 are Andrew Maragos, R-Minot; Marvin Nelson, D-Rolla; Mary Schneider, D-Fargo; and Marie Strinden, D-Grand Forks.

Lower pot penalties?

Another House bill aims to lower penalties for college students caught with small amounts of marijuana on campus.

HB 1394, sponsored by Reps. Lois Delmore, D-Grand Forks, Thomas Beadle, R-Fargo, Kim Koppelman, R-West Fargo, and Hawken, would make the possession of one-half ounce to a full ounce of marijuana a Class B misdemeanor, down from its current designation as a Class B felony.

Possession of less than a half-ounce of marijuana would be charged as an infraction, rather than as a Class B misdemeanor.

If someone is found guilty of possession of an ounce or less of marijuana, the bill also calls for the conviction to be sealed by the court after two years if there are no further drug possession convictions.

Delmore said the bill is designed to make sure that the mistake of smoking pot in a dorm or elsewhere on campus isn’t one that haunts a student the rest of their lives.

“If you have something like that on your record, you have a hard time getting a job” or housing, she said.

http://www.inforum.com/news/3661275-backers-fire-attempt-get-medical-marijuana-legalized-nd