More Genetic Research into Chronic Pain

Almost every month, news emerges about another research study into gene therapy for dealing with chronic pain. Today's post from sciencedaily.com (see link below) looks at research published in Nature Medicine. It has identified a gene particularly associated with pain sensitivity and talks about an amino acid which can have a direct effect on the genetic process. Genetic science is not easy for the layman to understand and talking about molecular levels will probably leave you scratching your head but you can get the general idea. Always good to know that this sort of research is going on - hopefully we will see practical results soon.

New Way to Treat Chronic Pain, Suggested by Study
ScienceDaily (Mar. 26, 2012)

Nearly one in five people suffers from the insidious and often devastating problem of chronic pain.

That the problem persists, and is growing, is striking given the many breakthroughs in understanding the basic biology of pain over the past two decades. A major challenge for treating chronic pain is to understand why certain people develop pain while others, with apparently similar disorders or injuries, do not. An equally important challenge is to develop individualized therapies that will be effective in specific patient populations.

Research published online in Nature Medicine points to solutions to both challenges. A research team led by Prof. Jeffrey Mogil of McGill University in Montreal and Prof. Michael Salter of The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, has identified a major gene affecting chronic pain sensitivity. The findings also suggest a new approach to individualizing treatment of chronic pain.

The gene that the researchers identified encodes the pain receptor known as P2X7. Specifically, the scientists discovered that a single amino-acid change in P2X7 controls sensitivity to the two main causes of chronic pain: inflammation and nerve damage.

The amino-acid change is known to affect only one function of P2X7 receptors -- the forming of pores that permit large molecules to pass through -- while leaving intact the other function, of allowing much tinier ions to flow through. Using a peptide that targets pore formation only, the researchers found that pain behaviours were dramatically reduced.

The scientists then examined genetic differences among human patients suffering from two distinct types of persistent pain: chronic post-mastectomy pain and osteoarthritis. In both cases, they found that individuals with genetically inherited low pore formation in P2X7 receptors experienced lower pain levels.

"Our findings indicate that it may be possible to develop drugs that block pores in this crucial receptor, while leaving its other function intact -- thereby killing pain while minimizing side effects," said Prof. Mogil, E.P. Taylor Professor of Pain Research in McGill's Department of Psychology.

Prof. Salter, Anne and Max Tanenbaum Chair in Molecular Medicine at SickKids, said these discoveries "point toward a new strategy for individualizing the treatment of chronic pain." Scientists from the U.S. and Israel also contributed to the study.

The study was supported by the Krembil Foundation, the Louise and Alan Edwards Foundation, the US National Institutes of Health (NIH), the Canadian Institutes of Health Research (CIHR) and SickKids Foundation.

http://www.sciencedaily.com/releases/2012/03/120326132539.htm

Glucose-Lowering Drugs for Neuropathy

Today's post from natap.org (see link below) looks at the results of a study into the possibility of non-insulin based, glucose reducing drugs being used to reduce the progression of neuropathy. These were brought to light at the recent Conference on Retroviruses and Opportunistic Infections (CROI). These drugs are widely given for the treatment of diabetes (itself a major cause of sensory neuropathy) but it seems they may well have a positive effect on the progression of HIV-related neuropathies. The article is not particularly easy to understand but then it was never meant to be - this sort of research paper isn't really designed to be light reading over the cornflakes. Hopefully, the research will lead to speedy implementation and widespread access to the drugs but as with all of these things...it may be some years yet!

Glucose-Lowering Drugs May Limit Progression to Symptomatic Peripheral Neuropathy
19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle: Mark Mascolini

Noninsulin glucose-lowering drugs may stall progression from mild peripheral neuropathy to symptomatic peripheral neuropathy, according to results of a study involving AIDS Clinical Trials Group (ACTG) A5001 participants [1]. The investigators confirmed that stavudine and didanosine heightened the risk of progression to symptomatic neuropathy--but protease inhibitors did not.

Sensory neuropathies remain the most frequent neurologic disorder associated with HIV infection and antiretroviral therapy (ART), noted Scott Evans (Harvard School of Public Health) and colleagues at other centers. Pain is the most common symptom of sensory neuropathy with HIV; other symptoms include numbness, paresthesia (tingling or pricking), and burning. There are no FDA-licensed agents for HIV-associated sensory neuropathies.

This study involved almost 1600 people in the ACTG Longitudinal Linked Randomized Trials (ALLRT), a meta-study of people enrolled in ACTG clinical trials. All these people were naive to antiretrovirals when they signed up for an ACTG trial, and all had neuropathy data recorded, including the Brief Peripheral Neuropathy Screen [2,3] administered as part of ALLRT every 48 weeks by trained personnel. Evans and coworkers defined peripheral neuropathy as "at least mild loss of vibration sensation in both great toes or absent or hypoactive ankle reflexes bilaterally relative to knees." They defined symptomatic peripheral neuropathy as peripheral neuropathy plus any bilateral symptoms.

The investigators devised two models to explore associations between peripheral neuropathy and progression to symptomatic peripheral neuropathy. The first model considered 1592 antiretroviral-naive ACTG trial participants, 80% men, 45% white, 32% black, 42% between 30 and 39 years old at first neurologic assessment, and 30% between 40 and 49. Median pretreatment viral load and CD4 count were 80,000 copies and 213. The second model considered 374 antiretroviral-naive people, 80% men, 43% white, 36% black, 30% between 30 and 39 at first neurologic assessment, and 39% between 40 and 49. Median pretreatment viral load and CD4 count were 100,000 copies and 166. Only about 10% of people in either model group had a history of injection drug use.

In the first model, people with peripheral neuropathy had a 58% higher risk of progressing to symptomatic peripheral neuropathy than did people without peripheral neuropathy (odds ratio [OR] 1.58, 95% confidence interval [CI] 1.08 to 2.29, P= 0.027). In the second model, people taking ART including didanosine or stavudine had a doubled risk of progression to symptomatic peripheral neuropathy (OR 2.16, 95% CI 1.21 to 3.85, P = 0.009). In this model using a noninsulin glucose-lowering drug cut the risk of progression to symptomatic peripheral neuropathy almost 90% (OR 0.12, 95% CI 0.02 to 0.83, P = 0.031).

Protease inhibitor use did not correlate with progression from peripheral neuropathy to symptomatic neuropathy. Neither did age, race, gender, pretreatment CD4 count or viral load, HCV positivity, or injection drug use. There was a nonsignificant trend toward an association with diabetes and neuropathy progression.

The investigators suggested that the association between glucose-lowering drugs and lack of neuropathy progression "could potentially have considerable clinical prevention effect." They cautioned that, because of the study's observational nature, the associations they identified may not be causal.

References

1. Evans S, Lee A, Ellis R, Chen H, Wu K, Bosch R, Clifford D. Progression to symptoms of peripheral neuropathy in HIV: suggested protection with use of glucose-lowering drugs. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 478. http://www.retroconference.org/2012b/PDFs/478.pdf.

2. Ellis RJ, Evans SR, Clifford DB, et al. Clinical validation of the NeuroScreen. J Neurovirol. 2005;11:503-511. http://informahealthcare.com/doi/abs/10.1080/13550280500384966.

3. Simpson DM, Kitch D, Evans SR, et al. HIV Neuropathy Natural History Cohort Study: Assessment measures and risk factors. Neurology 2006;66:1679-1687. http://www.neurology.org/content/66/11/1679.abstract.

http://www.natap.org/2012/CROI/croi_81.htm

Acupressure for Neuropathy

Today's video comes from eHow.co.uk and talks about the value of acupressure for neuropathic symptoms. As you know, acupressure and acupuncture are two different things. Acupressure doesn't use needles but uses manipulation on and around the various recognised acupressure points over the body to achieve the same effect. It may be less stressful than acupuncture and may be something a friend or family member can do after watching the video. You could call it directed massage!

Acupressure For Neuropathy -- powered by ehow

An HIV/Neuropathy Personal Story

Today's post is a video interview with a person living with both HIV and neuropathy from 1html.net (see link below). Even though everyone's story is different, personal to themselves and reveals different experiences of HIV; it will strike a chord with many people if only because of the effects stress can have on your well-being. The transcript of the video is reproduced below.




Transcript

Pamela Curry: Hello! My name is Pamela Curry. I became HIV positive via sexually transmitted means. I was going to a hospital to go about a procedure and they tested me for HIV and that's when I tested positive and of course I remember where it came from. Because I most of the time practiced safe sex, but he was so unpleasant that he was playing that slide and so the time over I got it from. At first I was angry, upset and that got even worse when I lost my job two weeks later because the company I worked for was self insured and unfortunately this is a right to work state. So when the paper work got to the home office, they found a reason to terminate me. Now because I want a fixed income, I have to seek out housing that will accept housing assistance for persons with HIV AIDS. And a lot of companies won't take that. So that means you have to live in somewhat less lower standard than you what may have been accustomed to before. Since testing positive -- to mention the word stress I break out into shingles. I have very severe attacks of shingles. In recent years I have felt personal neuropathy that I started at beginning. So then there are mornings where I can't get out of bed and I have to crawl to the bathroom. I was trying to compose myself and get myself to a position where people will not notice before I go venturing outside. Female Speaker: You take a number of medications?Pamela Curry: A little -- this pill twice a day. I have my medicine carrying it right here, here is about 20 pills. Some of them are -- one in particular typically causes nausea, sometimes frequent diarrhea. The most severe it comes over you just like that, but it is medication related and I know what meds call it, but I have to have them. So you deal with it the best you can. When you are HIV positive you are more susceptible to lots of infections and that includes common infections that 20 like -- Herpes, 20% population has it but not all of them, because it is not active. When you are HIV positive your immune system is compromised and you are going to have outbreaks more frequently and that will also -- I have the shingles more frequently. I have to take a higher dose of Valtrex to try to prevent it and even with the higher dose of Valtrex that doesn't mean you are not going to have a break out. It means you have to go to specialist instead of just your general practitioner and always use a protected sex. I know the current -- Administration's guidelines are to teach abstinence only and you are supposed to talk about the failure rate of condoms are 14%. But a condom only fails 14% and abstinence only, only works a 100% when it is practiced to 100%. And reality is 80% of teenagers do not continue to practice abstinence a 100% of the time. They are going to have sex and if haven't provided them with the tools to protect themselves, that become a risk.

http://www.1html.net/19360/Pamela_Curry_Hello_My_name_is_Pa.html

Neuropathy Questions and Answers for Beginners

Today's post from bismarcktribune.com (see link below) is a good basis for patients' questions and answers when they first realise something's going on with their feet. Helpful when deciding what to ask the doctor at a first appointment.

An explanation of peripheral neuropathy
Dr. Stephanie Miller | Posted: Sunday, March 25, 2012

Why do my hands and feet tingle and burn?

Peripheral neuropathy is one of the primary causes of tingling, burning and/or numbness in hands and/or feet. Nerves in the peripheral nervous system send information from the brain and spinal cord to other parts of the body and back again. If nerves are damaged, peripheral neuropathy can result. It most commonly starts in the longest nerves that reach to your toes. Depending on which nerves are affected, symptoms may vary.

Does peripheral neuropathy affect only hands and feet?

The tingling or numbness usually begins in the hands or feet but it may spread up into the legs and arms. It can turn into burning or jabbing pain. Skin may become extremely sensitive to touch. If motor nerves are impacted, muscle weakness or paralysis is possible. If autonomic nerves are affected, bowel or bladder problems may develop. Peripheral neuropathy can affect only one nerve or it may affect many nerves.

Who is at risk for peripheral neuropathy?

At least 50 percent of people with diabetes develop some form of neuropathy. Others commonly at high risk are alcoholics, who often have vitamin deficiencies due to poor dietary choices; people with autoimmune diseases such as rheumatoid arthritis and lupus; those exposed to toxic substances, certain medications, viral or bacterial infections, and nerve trauma such as repetitive sports injuries or accidents where nerves are damaged.

When should I see a doctor?

Any time you notice tingling, weakness or pain in your hands or feet, you should make an appointment with a primary care doctor or a neurologist, a doctor that specializes in disorders of the nervous system. Because peripheral neuropathy isn't a single disease, it can be difficult to diagnose. Determining the location of the nerve damage and its cause is important for successful treatment.

How does a doctor treat peripheral neuropathy?

When your doctor determines the cause of your peripheral neuropathy and treats that underlying cause, the neuropathy often improves. Several different prescription medications can reduce the pain. Your doctor will evaluate the degree of your neuropathy and work with you to find the best medications for your particular symptoms and type of neuropathy.

What can I do to reduce symptoms?

Wear soft cotton socks and shoes with good padding and support. A hand or foot massage improves circulation, stimulates nerves and may decrease pain. If you have diabetes, good control of your sugar is necessary. If you smoke, quit. Smoking affects circulation, increasing your risk of foot problems and possible amputation. Healthy eating is essential because vitamin deficiencies can cause or increase neuropathy symptoms. Preventing further nerve damage is essential. The right kind of regular exercise can reduce pain. Talk to your doctor about a healthy eating and exercise plan.

(Dr. Stephanie Miller is a neurologist at Bismarck Medcenter One Q&R Clinic. A graduate of the University of North Dakota School of Medicine and Health Sciences at Grand Forks, she completed an internship in internal medicine and a residency in neurology at Mayo School of Graduate Medicine, Rochester, Minn.)

http://bismarcktribune.com/lifestyles/health-med-fit/an-explanation-of-peripheral-neuropathy/article_feb9a1aa-736d-11e1-8ace-0019bb2963f4.html

Medical Marijuana for Neuropathic Pain

As a follow-up to yesterday's article; today's post is an informative video from videojug.com (see link below) about the various medical benefits of medical marijuana, including of course neuropathic pain. The video comes with written information which is reproduced below.

Medical Marijuana Benefits

David G. Ostrow (Medical Marijuana Doctor) gives expert video advice on: What conditions can marijuana treat?; Do most physicians believe in the power of medical marijuana to treat illness?; Why Is medical marijuana an effective way to treat nausea? and more...


What conditions can marijuana treat?

Medical cannabis has been used to treat many many conditions over the several millennia that it's been used. However, in modern day medicine - which is evidence based - I think the best science is in the area of pain reduction or analgesia. It is a non-addictive alternative to opiate drugs for peripheral neuropathy which doesn't respond very well to the typical opiate drugs. And that peripheral neuropathy is most typical in persons with HIV and/or diabetes. It's useful for the anorexia, nausea, that's directly caused by the disease or caused by medications for diseases- such as cancer chemotherapy. A number of trials have shown that it's very effective for cancer pain in terminal cancer. After that I would say multiple sclerosis is one of the areas where it's most widely used. Some people have recommended it for glaucoma, but there are some pretty potent drugs for glaucoma that are typically used and don't require ingesting a compound like marijuana or THC, so that seems to be the preferred way to use it.

Do most physicians believe in the power of medical marijuana to treat illness?

Most physicians will not admit to believing that marijuana or medicinal cannabis is useful except in very rare instances. This, I think, is the result of the misinformation and myths about marijuana and medical marijuana that have been propagated by the US government ever since the war on drugs began back in 1937. And the fact that the double blind placebo controlled study that is just now coming out and people who have spent their lives believing that marijuana is a highly addictive and dangerous substance are not likely to read or even believe that data. So I think we have a long way to go in educating America's physicians, nurses, health care practitioners about the truth and the usefulness of medicinal cannabis so that they will feel more comfortable using it. And that really is the purpose of the organization, The Medical Marijuana Policy Advocacy Project that I and others have established.

Why Is medical marijuana an effective way to treat nausea?

Medical marijuana is an effective way to treat nausea because it can be very easily titrated by the patient, most of whom only require a few puffs of smoke or a small amount of vaporized gas from marijuana. It doesn't have other side effects and it will not only treat the nausea but it will increase appetite, where anorexia often goes along with chronic nausea with cancer or chemotherapy. And so you're really getting two benefits at the same time.

How does medical marijuana help people with glaucoma?

Medical marijuana is supposed to decrease intraocular pressure which is the actual cause of glaucoma or the pathogenesis of it. The mechanism I'm not exactly sure of. It opens, it presumably opens up the canals through which the excess intraocular fluid can drain, but at the same time, we have topical agents that are very strong and very effective. They're usually prostaglandin derived compounds. And so I don't think that [unintelligible] cannabis is going to get very widely used in this area.

What do HIV and AIDS experts say about medical marijuana?

I would say that if you surveyed all the different medical specialties, it would be the HIV/AIDS and oncologists that would be most enthusiastic and positive about medicinal cannabis. At least in those states, like California, that have state sanctioned and regulated medicinal cannabis programs. The majority of patients on those programs are HIV positive patients. They use it primarily for pain relief, but the so-called side effects of euphoria, of increased appetite, well-being, etc., are just as important as the pain-relieving properties in HIV-related disease.

How is medical marijuana used in the treatment of Alzheimer's patients?

Medical marijuana is not yet in clinical trials for Alzheimer's. There's early laboratory evidence that in rats or in in vitro cultures that exposure to whole extracts and perhaps some individual components of marijuana may interfere with the formation of the amyloid deposits and fibulary tangs that are diagnostic of Alzheimer's disease. But I do not know of any clinical trials in humans that have looked at this. They would be very difficult to do because we know that Alzheimer's is a long-term chronic disease that actually begins long before there is any clinical evidence of it being there. So you would have to start with people at high risk of Alzheimer's disease and follow them for many years to determine marijuana's effectiveness there.

Is there an effective way to inhale marijuana without smoking it?

The best way health wise; and particularly for people who find that their throat or lungs are irritated by smoke from marijuana, is to vaporize it. And that is to put it in a chamber and expose it to a very high level of heat so the compounds are paralyzed or released as a gas rather than burnt. And then that gas is collected and allowed to cool. And then you just breath it as if you were breathing air from a plastic balloon, or a rubber balloon or something. And that is basically what vaporization is all about. And that's an alternative that the American Institute of Medicine is recommended. They did research on that as an alternative delivery mechanism. But the federal government has not been willing to fund those kinds of studies. Although there are some being conducted with private funds.

http://www.videojug.com/interview/medical-marijuana-benefits-2

Non-smokers Can Benefit From Cannabis-based Neuropathy Relief Too

Non-smokers and ex-smokers have often been put off trying cannabis for the relief of neuropathic pain (the laws of the land are often a discouraging factor too!) because of the potential damage to their lungs. However, using a vaporizer may well be the answer as it apparently delivers the same amount of THC, with the same biological effects, without the inhaling of tobacco, or other toxins normally associated with smoking. As always, assuming that you are able to access regular marijuana, the decision has to be made as to whether the benefits outweigh the risks. This article comes from imarijuana.com (see link below).

Same Level Of THC and Fewer Toxins with Marijuana Vaporizer
Posted on 22 November, 2011 by admin

According to researchers from the University of California San Francisco, a smokeless cannabis-vaporizing device delivers the same level of active therapeutic chemical and produces the same biological effect as smoking cannabis.

Results of a UCSF study that focuses on delivery of the active ingredient delta-9-tertrahydrocannibinol, or THC, are reported in the online issue of the journal “Clinical Pharmacology and Therapeutics.”

“We showed in a recent paper in the journal ‘Neurology’ that smoked cannabis can alleviate the chronic pain caused by HIV-related neuropathy, but a concern was expressed that smoking cannabis was not safe. This study demonstrates an alternative method that gives patients the same effects and allows controlled dosing but without inhalation of the toxic products in smoke,” said study lead author Donald I. Abrams, MD, UCSF professor of clinical medicine.

The team of researchers looked at the effectiveness of a device that heats cannabis to a temperature between 180 and 200 degrees C, just short of combustion, which occurs at 230 degrees C. Eighteen individuals were enrolled as inpatients for six days under supervision in the General Clinical Research Center at San Francisco General Hospital Medical Center. The participants received three different strengths of cannabis on different days by two delivery methods–smoking or vaporization–three times a day, under the study protocol.

THC plasma concentrations were measured along with the exhaled levels of carbon monoxide, or CO, which served as a marker for the many other combustion-generated toxins inhaled when smoking.

“Using CO as an indicator, there was virtually no exposure to harmful combustion products using the vaporizing device. Since it replicates smoking’s efficiency at producing the desired THC effect using smaller amounts of the active ingredient as opposed to pill forms, this device has great potential for improving the therapeutic utility of THC,” said study co-author Neal L. Benowitz, MD, UCSF professor of medicine, psychiatry and biopharmaceutical sciences.

Benowitz added that pills tend to provide patients with more THC than they need for optimal therapeutic effect and increase side effects.

“By a significant majority, patients preferred vaporization to smoking, choosing the route of delivery with the fewest side effects and greatest efficiency,” said Benowitz.

Co-authors include Cheryl A. Jay, MD, UCSF neurology; and Starley B. Shade, MPH; Hector Vizoso, RN; and Mary Ellen Kelly, MPH, UCSF Positive Health Program at San Francisco General Hospital Medical Center.

The study was funded by the University of California’s Center for Medicinal Cannabis Research.
Reference:University of California – San Francisco

http://www.imarijuana.com/tag/smoked-cannabis

Neuropathy and Exercise

Today's article comes from peripheralneuropathydoctor.info (see link below) which is a Kentucky medical and rehab clinic/practice website and although this blog normally rejects anything that seems like an advertisement, the advice given here is completely sound and reliable. It's very easy for neuropathy patients to give up on exercise but absolutely unwise for your health, despite the pain and discomfort that may result from activity. Doing what you can, according to your own ability, is always better than doing nothing.

Neuropathy and Exercise
March 7th 2012

If you suffer from neuropathy, you know that the pain, muscle control problems, and overall health complications can make even everyday activities harder to manage. For some, the prospect of exercising while suffering from neuropathy will seem not only unrealistic but an almost ironic misplacement of priorities. Exercise is important for everyone, though, and in sufferers of neuropathy, can help control blood sugar and actually slow down the progression and symptoms of the condition!

Exercising regularly greatly decreases anyone’s risk of diabetic neuropathy, and has been shown to control symptoms and deterioration in sufferers by elevating overall blood flow to the limbs and controlling cardiovascular atrophy. Depending on your specific type of neuropathy, areas affected, and the extent of the damage, you will have to adjust conventional workout routines to accommodate the condition. Ask your NeuropathyDR® clinician if you have questions, and be sure to consult them before beginning any workout program. Your clinician will inspect your feet and legs for signs of potential problems, and will help you make sure your shoes are properly fitted so as to avoid neuropathy-related injuries.

Additionally:
•Use silica gel or air midsoles
•Use polyester or polyester/cotton blend socks to keep your feet dry
•Avoid any workout clothes that rub against your skin in the same area.

Ann Albright of the Division of Diabetes Translation in Atlanta cautions that neuropathy patients will want to steer clear of most repetitive or weight-bearing exercise, such as running, walking, or extensive weight training (although some sources advocate weight training as beneficial, in moderation). So which exercises are the most beneficial while reducing risk?

Don’t Neglect Stretching and Core Activities…

Swimming is one of the best exercises, as it is an activity adaptable to any age, fitness level, or degree of neuropathy symptoms. Swimming is also a full-body, “no-impact” workout, and so is less harmful to your joints, legs, and feet than most other forms of exercise, without sacrificing circulation (ask any lap swimmer and they’ll tell you—swimming has no problem getting your heart rate up!) As such, it is highly recommended for almost anyone.

Bicycling, rowing, and use of a stationary bicycle are other excellent, low-impact activities that can be safely integrated into a neuropathy treatment program. Some organizations have even developed exercise programs for senior citizens suffering from neuropathy, incorporating a heavy emphasis on seated exercises.

If you don’t have regular access to facilities or equipment for more extensive exercise, there are some basic exercises you can do almost anywhere that can help your neuropathy! Here are some to try:
•For your hands, touch the pad of your thumb with your index finger, running the finger down to the base of your thumb. Then, repeat the movement with the index, middle, ring, and little fingers. Do this exercise several times.
•For your legs and feet, straighten one knee and point your foot. Flex your ankle five times, then circle your foot five times in each direction, clockwise and counterclockwise.
•To increase balance, try this exercise: from a standing position, rise up slowly on your tiptoes, and then rock backward onto your heels. Keep your knees straight, but try not to lock them.


Gentle massage & manual stimulation in the clinic helps speed recovery…


Additional precautions are vital for neuropathy patients to observe. After every workout session, patients should remember to check their feet and any relevant extremities for blisters, irritation, or sores. These could be vulnerable to infections, which themselves could elevate risk for amputation.

It is important for neuropathy sufferers to be mindful of their heart rate and blood pressure. Especially if you suffer from autonomic neuropathy, which can greatly increase risk of heart failure or cardiac arrest, be aware of your limitations when it comes to safe exercise. Don’t worry—there’s a way for everyone to exercise safely. If you have any doubts, consult your NeuropathyDR® clinician to review your workout plan.

Finally, be sure to monitor your body temperature. Neuropathy sufferers are at high risk when it comes to overheating, since some types of neuropathy can reduce the body’s ability to temperature-control. Consult your clinician if sweating seems overly profuse or the opposite, less than normal.

If you have any questions about exercising with neuropathy, contact us! We can answer your questions and help put you in touch with a NeuropathyDR® clinician who can help you in person. Have a great workout!

http://www.peripheralneuropathydoctor.info/?m=201203

Food Allergies and Neuropathy

It is mostly overlooked in articles about neuropathy but if a lack of Vitamin B12 for instance, is thought to be one of the causes of neuropathy, then why not certain food allergies too? Today's article from myiho.com, which is a Florida based neuropathy blog, (see link below) looks at the theory that certain food allergies may be primary causes of nerve damage. Aspartame, for instance, as one of the commonest ingredients of sweeteners, may surprise you.

Nutrition’s Role in Neuropathy
Posted on March 7, 2012

Neuropathy has wide variety of causes, and nutritional causes are a major subset of it. Neuropathy secondary to deficiency of Vitamin B (especially B12 and Folic Acid) is well known and one of the first suspicion in otherwise normal patients presenting with symptoms of neuropathy like numbness, pin-and-needle sensation, burning sensations, pain or loss of sensations. When it affects the nerves supplying the muscles, it may result in weakness of muscle, muscle atrophy, lack of fine muscle control which may result in many symptoms depending on which muscles are affected.

But one cause of peripheral neuropathy that is not readily thought to be associated with neuropathy is food allergy. The association between food allergy and neuropathy is often overlooked because only recently conclusive evidence from research has become available establishing a certain link between neuropathy and allergic response to certain food items. The culprits so far found to be most commonly occurring are derivatives of glutamic acid and aspartic acid, gluten, pesticides on fruits and vegetables, food coloring dyes. One very common artificial sweetener, Aspartame, is used in fruit juices, diabetic food and numerous other products. It is one of the most commonly recognized allergen triggering symptoms of neuropathy like tingling, numbness, burning sensation etc. and also affecting auditory nerve causing tinnitus. Consumption of large quantities greatly increases the chances of having the neuropathy. Often, stopping the consumption of aspartame cures the symptoms almost entirely.

Many more agents commonly found in food may cause allergic response which may present as neuropathy. The ones that are currently believed to be responsible for most of the cases are Azino-moto (Mono Sodium Glutamate) which is commonly used in Chinese foods, gluten found in wheat containing edible items, some coloring dyes used in foods. Not only these, but normal fully natural food items like fruits, eggs, and milk may be the cause of food allergy induced neuropathy. Often it may happen, that the tracking of the allergy causing food item may not be very simple and straightforward.

So what if your neuropathy is suspected to be due to food allergy. Main diagnostic test used is a Radioallergosorbent Test (RAST Test) which detects antibodies against “common” food allergens. Since not all antigens could be detected in 100% of cases, sometimes the treatment may involve just hit and trial in which suspected food items are stopped for few week and observed whether it alleviates the neuropathy. Also it would be advisable to stop common known allergens like aspartame, MSG, food dyes, and gluten and observe if the symptoms are alleviated by this. Also thoroughly wash fruits and vegetables before consuming, as pesticides present on them could be the cause.

If you are one of the many thousands of sufferers of Neuropathy, you know all to well that numbness and tingling is still a pain to deal with. Peripheral Neuropathy is a condition that is characterized by altered sensation or a change in motor control of a body part. The nerve becomes irritated or damaged and it no longer conducts the messages it should. If your neuropathy is left untreated, it will begin to affect your quality of life.

http://myiho.com/orlandoneuropathyblog/?m=201203

Repairing Damaged Nerves - New Developments

You may have to stretch your imagination somewhat to see how the treatments talked about in today's article from sciencedaily.com (see link below) will eventually lead to simple treatments for our sort of neuropathy. However, you can follow the logic and because these scientists are dealing with worst-case-scenarios in terms of nerve damage, it is to be hoped that certain principles may eventually be applied to less traumatic neuropathies. In our case we'll have to wait for top-down solutions. Nerve damage caused by war or accident wounds is clearly of a different order than the neuropathy we suffer from with whole bodies but one would think that all progress in nerve repair, will eventually be relevant to us.

Step Forward in Effort to Regenerate Damaged Nerves
ScienceDaily (Feb. 21, 2012)

The carnage evident in disasters like car wrecks or wartime battles is oftentimes mirrored within the bodies of the people involved. A severe wound can leave blood vessels and nerves severed, bones broken, and cellular wreckage strewn throughout the body -- a debris field within the body itself.

It's scenes like this that neurosurgeon Jason Huang, M.D., confronts every day. Severe damage to nerves is one of the most challenging wounds to treat for Huang and colleagues. It's a type of wound suffered by people who are the victims of gunshots or stabbings, by those who have been involved in car accidents -- or by soldiers injured on the battlefield, like those whom Huang treated in Iraq.

Now, back in his university laboratory, Huang and his team have taken a step forward toward the goal of repairing nerves in such patients more effectively. In a paper published in the journal PLoS ONE, Huang and colleagues at the University of Rochester Medical Center report that a surprising set of cells may hold potential for nerve transplants.

In a study in rats, Huang's group found that dorsal root ganglion neurons, or DRG cells, help create thick, healthy nerves, without provoking unwanted attention from the immune system.

The finding is one step toward better treatment for the more than 350,000 patients each year in the United States who have serious injuries to their peripheral nerves. Huang's laboratory is one of a handful developing new technologies to treat such wounds.

"These are very serious injuries, and patients really suffer, many for a very long time," said Huang, associate professor of Neurosurgery and chief of Neurosurgery at Highland Hospital, an affiliate of the University of Rochester Medical Center. "There are a variety of options, but none of them is ideal.

"Our long-term goal is to grow living nerves in the laboratory, then transplant them into patients and cut down the amount of time it takes for those nerves to work," added Huang, whose project was funded by the National Institute of Neurological Disorders and Stroke and by the University of Rochester Medical Center.

For a damaged nerve to repair itself, the two disconnected but healthy portions of the nerve must somehow find each other through a maze of tissue and connect together. This happens naturally for a very small wound -- much like our skin grows back over a small cut -- but for some nerve injuries, the gap is simply too large, and the nerve won't grow back without intervention.

For surgeons like Huang, the preferred option is to transplant nerve tissue from elsewhere in the patient's own body -- for instance, a section of a nerve in the leg -- into the wounded area. The transplanted nerve serves as scaffolding, a guide of sorts for a new nerve to grow and bridge the gap. Since the tissue comes from the patient, the body accepts the new nerve and doesn't attack it.

But for many patients, this treatment isn't an option. They might have severe wounds to other parts of the body, so that extra nerve tissue isn't available. Alternatives can include a nerve transplant from a cadaver or an animal, but those bring other challenges, such as the lifelong need for powerful immunosuppressant drugs, and are rarely used.

One technology used by Huang and other neurosurgeons is the NeuraGen Nerve Guide, a hollow, absorbable collagen tube through which nerve fibers can grow and find each other. The technology is often used to repair nerve damage over short distances less than half an inch long.

In the PLoS One study, Huang's team compared several methods to try to bridge a nerve gap of about half an inch in rats. The team transplanted nerve cells from a different type of rat into the wound site and compared results when the NeuraGen technology was was used alone or when it was paired with DRG cells or with other cells known as Schwann cells.

After four months, the team found that the tubes equipped with either DRG or Schwann cells helped bring about healthier nerves. In addition, the DRG cells provoked less unwanted attention from the immune system than the Schwann cells, which attracted twice as many macrophages and more of the immune compound interferon gamma.

While both Schwann and DRG cells are known players in nerve regeneration, Schwann cells have been considered more often as potential partners in the nerve transplantation process, even though they pose considerable challenges because of the immune system's response to them.

"The conventional wisdom has been that Schwann cells play a critical role in the regenerative process," said Huang, who is a scientist in the Center for Neural Development and Disease. "While we know this is true, we have shown that DRG cells can play an important role also. We think DRG cells could be a rich resource for nerve regeneration."

In a related line of research, Huang along with colleagues in the laboratory of Douglas H. Smith, M.D. , at the University of Pennsylvania are creating DRG cells in the laboratory by stretching them, which coaxes them to grow about one inch every three weeks. The idea is to grow nerves several inches long in the laboratory, then transplant them into the patient, instead of waiting months after surgery for the nerve endings to travel that distance within the patient to ultimately hook up.

http://www.sciencedaily.com/releases/2012/02/120221125018.htm

Targeting Neuron Memories to Treat Neuropathy

Today's post from Sciencedaily.com (see link below) looks at how traces of pain can be remembered by the brain. We're all familiar with the pain someone feels in a limb that has been removed or lost and this is basically because the brain remembers a 'reality', as if the limb were still there. Scientists are looking at how the manipulation of the protein kinase PKMzeta could possibly lead to a 'switching off' of the pain memory associated with nerve damage. If the protein can be targeted to block certain pain pathways, who knows what treatment possibilities may emerge.

Neuron Memory Key to Taming Chronic Pain, New Research Suggests
ScienceDaily (Feb. 13, 2012)

For some, the pain is so great that they can't even bear to have clothes touch their skin. For others, it means that every step is a deliberate and agonizing choice. Whether the pain is caused by arthritic joints, an injury to a nerve or a disease like fibromyalgia, research now suggests there are new solutions for those who suffer from chronic pain.

A team of researchers led by McGill neuroscientist Terence Coderre, who is also affiliated with the Research Institute of the McGill University Health Centre, has found the key to understanding how memories of pain are stored in the brain. More importantly, the researchers are also able to suggest how these memories can be erased, making it possible to ease chronic pain.

It has long been known that the central nervous system "remembers" painful experiences, that they leave a memory trace of pain. And when there is new sensory input, the pain memory trace in the brain magnifies the feeling so that even a gentle touch can be excruciating.

"Perhaps the best example of a pain memory trace is found with phantom limb pain," suggests Coderre. "Patients may have a limb amputated because of gangrene, and because the limb was painful before it was amputated, even though the limb is gone, the patients continue to feel they are suffering from pain in the absent limb. That's because the brain remembers the pain. In fact, there's evidence that any pain that lasts more than a few minutes will leave a trace in the nervous system." It's this memory of pain, which exists at the neuronal level, that is critical to the development of chronic pain. But until now, it was not known how these pain memories were stored at the level of the neurons.

Recent work has shown that the protein kinase PKMzeta plays a crucial role in building and maintaining memory by strengthening the connections between neurons. Now Coderre and his colleagues have discovered that PKMzeta is also the key to understanding how the memory of pain is stored in the neurons. They were able to show that after painful stimulation, the level of PKMzeta increases persistently in the central nervous system (CNS).

Even more importantly, the researchers found that by blocking the activity of PKMzeta at the neuronal level, they could reverse the hypersensitivity to pain that neurons developed after irritating the skin by applying capsaicin -- the active ingredient in hot peppers. Moreover, erasing this pain memory trace was found to reduce both persistent pain and heightened sensitivity to touch.

Coderre and his colleagues believe that building on this study to devise ways to target PKMzeta in pain pathways could have a significant effect for patients with chronic pain. "Many pain medications target pain at the peripheral level, by reducing inflammation, or by activating analgesia systems in the brain to reduce the feeling of pain," says Coderre. "This is the first time that we can foresee medications that will target an established pain memory trace as a way of reducing pain hypersensitivity. We believe it's an avenue that may offer new hope to those suffering from chronic pain."

Other contributing researchers on this study include Andre Laferrière, Mark H Pitcher, Anne Haldane, Yue Huang, Virginia Cornea, Naresh Kumar, Fernando Cervero (all from the Alan Edwards Centre for Research on Pain at McGill) and co-author Todd C Sacktor (State University of New York Downstate Medical Center).

This research was supported by grants from Canadian Institutes of Health Research (CIHR), the Louise and Alan Edwards Foundation, National Institutes of Health (NIH) and an Astra-Zeneca/AECRP fellowship.

http://www.sciencedaily.com/releases/2012/02/120213154141.htm

It's OK to Treat HIV-Related Pain

Today's article from pain.com (see link below) discusses the fact that, as a general rule, HIV-related pain is not treated as well as it could be. There is a reluctance to treat pain with stronger drugs (opiates etc) either because they may be addictive, or because it's too expensive, or because it's culturally unpopular. Yet most pain can be controlled with careful administration of drugs (some neuropathy sufferers may disagree) and there's really no reason for patients to suffer unduly, or feel that they have to live through the pain. It's important to remember that we're talking about pain that lasts more than a few months (chronic pain) and not the everyday aches and pains that most people have.

Are HIV/AIDS Patients Undertreated for Pain?
December 15, 2011

Not all HIV/AIDS patients will suffer from chronic pain problems, but studies suggest that the prevalence of chronic pain is high in HIV/AIDS patients, with over half of HIV/AIDS patients reporting complaints such as chronic headaches, severe abdominal pain and peripheral neuropathy. The treatments for HIV/AIDS have improved drastically since the beginning of the HIV/AIDS epidemic, with antiretroviral drugs extending the lives of infected patients. These drugs transformed a diagnosis of HIV/AIDS from a death sentence into a struggle with a serious, yet manageable condition. The question still remains: Are the pain complaints of HIV/AIDS patients being addressed to the fullest potential, or are HIV/AIDS patients undertreated for pain?

Studies examining this question have come to the conclusion that pain is indeed undertreated in HIV/AIDS patients, even in developed countries with modern hospitals and the available resources to treat pain. It appears as though the two main agents we have for treating pain related to HIV/AIDS, opioid pain medications and antidepressant medications, are both prescribed to HIV/AIDS patients less than would be expected. Opioid pain medications, also called narcotics, are very effective at treating all types of pain except pain due to nerve damage. Antidepressants and certain types of anti-seizure medications are more effective for neuropathy and some chronic pain conditions in which narcotics are not a good long-term pain management solution. When rates of pain treatment in HIV/AIDS and cancer patients are compared, HIV/AIDS patients receive far less treatment for pain than cancer patients, even though prevalence rates for pain are similar in both diseases.

There are a lot of different reasons that can explain why pain is grossly undertreated in HIV/AIDS patients. In some cases, patients may not understand that their pain can be treated and effectively managed, so they might not seek help for their pain complaints. They may feel as though it is necessary to suffer through pain if you have HIV/AIDS and that nothing can be done about it, even though this is not true. Other patients may fear the side effects of pain medications or becoming addicted to narcotic pain medications. Other possibilities include the patient feeling as though they already have to take too many medications and that this may harm them, and lack of communication between the doctor and the patient. In some cases, the cost and availability of the medications may be an issue. Doctors may also fear being punished for prescribing pain medications to patients too often. Overall, the reasons why pain is undertreated in HIV/AIDS patients vary depending on many factors, but things can be done to improve the situation, including better communication between doctors and patients about pain management.

In undeveloped and developing countries, the situation is even worse for treatment of HIV/AIDS and the management of the pain involved with the disease. For example, in Kenya, HIV/AIDS treatment statistics have actually improved in a very short period of time. Twenty-five percent more people with HIV/AIDS have access to antiretroviral drugs in Kenya in 2011 than they did in 2010. Obviously, efforts to increase the availability of these drugs for HIV-infected people in Kenya has paid off. However, the availability of drugs such as morphine in tablet form for pain relief is incredibly low. Because of this, many HIV/AIDS patients can manage their disease with antiretroviral drugs, but their pain may go completely untreated regardless of the severity of the pain. There are also commonly issues with HIV-infected children suffering from chronic pain; doctors are reluctant to use morphine to treat a child, even if it means that not doing so will mean that the child has to live with chronic pain that could have been managed.

Palliative care and pain management are extremely important components of treatment for HIV/AIDS patients all over the world. Since there are so many different reasons why pain is undertreated in HIV/AIDS patients, there is no quick solution to the problem. However, improved communication between doctors and patients and increased availability of pain medications can improve the situation.

http://pain.com/library/2011/12/15-hivaids-patients-undertreated-pain/

Do Statins Cause Neuropathy?

There are other posts about statins and neuropathy on the blog (see list on the right) but this one from suite101.com (see link below) explains the problem clearly and poses the question as to whether statin drugs used to lower cholesterol are actually increasing problems for the nervous system. If you already have neuropathic problems, it's probably not a good idea to begin taking statin drugs but it's always advisable to discuss it with your doctor, especially if you have high levels of unhealthy cholesterol.

Statins Linked to Peripheral Neuropathies
Cholesterol Drugs Linked to Peripheral Neuropathies: Apr 2, 2010
Kathryn Picoulin

Statin drugs were considered the magic pill to reverse cardiovascular disease, but the serious side effects are mounting up enough to question if they're worth it.

More than 16 million people in the US, and more than 18 million around the world are currently taking statin drugs to lower their cholesterol levels. The first statin drug was approved in 1987. There are seven forms of statin drugs being prescribed around the world. The eighth statin drug, Baycol, was recalled in 2001 four years after its approval by the FDA due to the serious side effects and many lawsuits.

Lipitor, the world’s top selling statin drug brings in more than $12.7 billion a year. It is 100% synthetically made compared to most of the other statin drugs that are made from fungi. Mevacor (lovastatin) is derived from the Aspergillus fungus. (Statin Answers 2006-2010) Mevastatin, the source to make pravastatin, is derived from a strain of penicillin.

Statins work by blocking the enzyme in the liver that is involved in making cholesterol. This causes less cholesterol to be made. However, cholesterol is a vital substance required for the function of every cell in the body including the neurological system. Lowering cholesterol levels lower than what the body needs may end up causing more harm than good.

Research Studies Linking Statins to Peripheral Neuropathies

Current research has linked the use of statin drugs to the development of peripheral neuropathies. Peripheral neuropathy is a condition that develops from progressive damage to the peripheral nerves and affects the hands, feet, legs and arms. Common symptoms are loss of feeling in feet and or hands with some tingling, numbness and pain often causing unstable gait. There are more than 100 different forms of peripheral neuropathies identified so far.

Numerous studies have reported that peripheral neuropathies often developed in subjects that used statin drugs for a period of one to seven years. The incidence rate is one in 2200 persons and is often permanent even after stopping the statin drug.

Researchers studied over 500,000 individuals taking statin drugs. They found that taking statin drugs for one year increased their risk of developing neuropathies by 15%, after two years the risk rose to 26%.

Researchers at the Montreal Neurological Institute at McGill University found that statin drugs prevent the repair of the myelin sheath. (The American Journal of Pathology). Myelin is like a conductive insulator of the nervous system delivering messages between the brain and the rest of the body. Myelin is composed of more than 80% cholesterol and up to 20% protein. Cholesterol works to maintain the integrity of the myelin sheath.

Not long after statin drugs became global and after noting an increased rate of peripheral neuropathies in subjects using statin drugs a group of researchers reviewed 460,000 residents in a Danish community. They excluded all subjects with systemic illnesses that were prone to developing peripheral neuropathies as well. They found that people who took statin drugs were 14 times more likely to develop peripheral neuropathies than those who were not. Current research has increased the number to 16 times the risk. (Journal of the American Academy of Neurology)

Alternative Treatments Decrease Symptoms of Neuropathy

There are several alternative treatments that may help decrease the symptoms of peripheral neuropathies. Vitamins E, B1 and B12 have been shown to diminish tingling and pain stemming from neuropathy. B12 helps to maintain the integrity of the myelin sheath that protects nerves.

Alpha lipoic acid (found in spinach, broccoli potatoes and organ meats), omega-3 fatty acids and GLA (gamma linolenic acid) have all been shown in studies to reduce the symptoms of peripheral neuropathies and increase better blood flow to the areas of damage.

Evening primrose oil (contains GLA) was tested in three double blind studies. The finding showed mild improvement in the symptoms of neuropathy.

Studies at the University of Maryland Medical Center showed that acetyl-L-carnitine (L-carnitine) helps to not only diminish the symptoms of peripheral neuropathy but also helps the return of regular sensations in the extremities. L-carnitine is naturally found in peanut butter, dairy products and red meat; however, supplements of L-carnitine are more concentrated.

Acupuncture has been effective in most cases in easing the pain associated with peripheral neuropathies.

1. Journal of the American Medical Association (JAMA); “Vitamins for Chronic Disease Prevention in Adults,” Clinical Applications, Robert H. Fletcher, MD,MSc; Kathleen M. Fairfield, MD,DrPH

2. JAMA. 2002;287:3127-3129.

http://kathryn-picoulin.suite101.com/statins--linked-to-a-new-side-effect-a221061

Peripheral Neuropathy and the Brain (Vid)

An interesting and clearly explained video by Dr, David Schiller, talking about what is happening and where it occurs in the brain, when you have neuropathy. Not too long but now you will know where your burning or tingling or numbness is being registered and why the brain is confused.

Atripla and Neuropathy?

Today's post from doublecheckmd.com (see link below)is a bit worrying for Atripla users. Not usually on the list of anti retrovirals that can cause neuropathy, after reading this detailed break down of the drug, you may want to discuss the issue with your HIV-specialist. You may need to look a few terms up to find out what they refer to.

Atripla efavirenz/emtricitabine/tenofovir

Atripla may cause peripheral neuropathy (damage to nerves - may cause pain, numbness, tingling, weakness, loss of muscle control, burning, loss of feeling, dizziness, vision problems, digestive tract problems, bloating, constipation, urinary incontinence, incomplete bladder emptying; symptoms may start in the hands or feet) in more than 5% of people.
This drug may also cause the following symptoms that are related to peripheral neuropathy:
• Lack of energy/fatigue in 9% of people
• Burning, prickling, tickling or tingling in more than 5% of people
• Hepatitis
• Jaundice
• Liver failure
• Liver injury
• Low potassium levels
• Muscle destruction/damage
• Muscle weakness
• Nerve damage in more than 5% of people
• Numbness of the arms/legs
• Numbness or tingling in more than 5% of people


Medical Source Information
Words in italics indicate symptoms related to peripheral neuropathy.

Musculoskeletal side effects have included arthralgia and myalgia in at least 5% of patients receiving emtricitabine or tenofovir. Arthralgia, myalgia, and myopathy have been reported during postmarketing experience with efavirenz. Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, and myopathy have been reported during postmarketing experience with tenofovir.
Rhabdomyolysis, osteomalacia, muscular weakness, and myopathy may occur as a result of proximal renal tubulopathy.

Renal side effects have included new onset or worsening renal impairment with tenofovir. Renal insufficiency, renal failure, acute renal failure, Fanconi syndrome, proximal renal tubulopathy, increased creatinine, acute tubular necrosis, nephrogenic diabetes insipidus, and interstitial nephritis (including acute cases) have been reported during postmarketing experience with tenofovir.

Rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, and hypophosphatemia may occur as a result of proximal renal tubulopathy.

Nervous system side effects (Grades 2 to 4) have included dizziness (8%) and headache (6%). Selected side effects of moderate to severe intensity have included impaired concentration and somnolence in greater than or equal to 2% of efavirenz-treated patients. Nervous system symptoms of any grade and regardless of causality (53%) included dizziness (28.1%), insomnia (16.3%), impaired concentration (8.3%), somnolence (7%), abnormal dreams (6.2%), hallucinations (1.2%), amnesia, agitation, euphoria, depersonalization, confusion, abnormal thinking, and stupor during clinical trials of efavirenz in combination with other antiretroviral agents. These symptoms were mild in 33.3%, moderate in 17.4%, and severe in 2% of patients. Therapy was discontinued in 2.1% of patients due to these side effects. Paresthesia and peripheral neuropathy (including peripheral neuritis and neuropathy) have been reported in at least 5% of patients receiving emtricitabine or tenofovir. Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor, and tinnitus have been reported during postmarketing experience with efavirenz.

The most common side effects (any severity; greater than or equal to 10%) reported during a clinical study of efavirenz, emtricitabine, and tenofovir included diarrhea, nausea, headache, fatigue, dizziness, depression, insomnia, abnormal dreams, and rash. The most significant side effects associated with efavirenz are nervous system symptoms, psychiatric symptoms, and rash.

Other side effects (Grades 2 to 4) have included fatigue (9%). Pain (moderate to severe intensity; 2% or greater) has been reported with efavirenz. Fever, pain, and back pain have been reported in at least 5% of patients receiving emtricitabine or tenofovir. Asthenia has been reported during postmarketing experience with efavirenz and tenofovir. Contraceptive failure (with an implantable hormonal contraceptive) has been reported during postmarketing experience with efavirenz.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Efavirenz, emtricitabine, and tenofovir may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired. Call your doctor at once if you have any of these other serious side effects: signs of liver damage - nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); urinating less than usual or not at all; fever, chills, body aches, flu symptoms; unusual thoughts or behavior, severe depression, extreme fear, thoughts of hurting yourself or others, hallucinations; severe blistering, peeling, and red skin rash; or seizure (convulsions). Less serious side effects may include: dizziness, drowsiness, anxiety, depressed mood; headache, tired feeling, ringing in your ears, vision problems; sleep problems (insomnia), confusion, strange dreams, forgetfulness; mild nausea, vomiting, diarrhea, loss of appetite, upset stomach; darkened skin on the palms of your hands or the soles of your feet; joint pain, back pain; numbness or tingly feeling; runny or stuffy nose, cough; or changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist). This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Hepatic side effects have included elevated AST (greater than 180 units/L in males and 170 units/L in females; 3%) and ALT (greater than 215 units/L in males and 170 units/L in females; 2%). Elevated bilirubin (greater than 2.5 times ULN) has been reported in up to 3% of patients treated with emtricitabine or tenofovir. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogs, including tenofovir, in combination with other antiretrovirals. Hepatic enzyme increase, hepatic failure, and hepatitis have been reported during postmarketing experience with efavirenz. Hepatic steatosis, hepatitis, and increased liver enzymes (primarily AST, ALT, and gamma glutamyl transferase) have been reported during postmarketing experience with tenofovir. Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and hepatitis B after discontinuation of emtricitabine or tenofovir and were associated with liver failure and liver decompensation in some of the emtricitabine-treated patients.

Metabolic side effects have included hyperglycemia (greater than 250 mg/dL; up to 2%), altered serum glucose (less than 40 mg/dL or greater than 250 mg/dL; up to 3%), and elevated fasting cholesterol (greater than 240 mg/dL; up to 22%), creatine kinase (greater than 990 units/L in males and 845 units/L in females; up to 9%), serum amylase (greater than 175 units/L; up to 8%), fasting triglycerides (greater than 750 mg/dL; 4%), and alkaline phosphatase (greater than 550 units/L; 1%). Elevated pancreatic amylase (greater than 2 times ULN; up to 3%) and serum lipase (greater than 2 times ULN; up to 3%) have been reported in up to 3% of patients treated with emtricitabine or tenofovir. Increased body weight has also been reported. Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. Hypercholesterolemia and hypertriglyceridemia have been reported during postmarketing experience with efavirenz. Hypokalemia, lactic acidosis, and hypophosphatemia have been reported during postmarketing experience with tenofovir.

Hypokalemia and hypophosphatemia may occur as a result of proximal renal tubulopathy.

Side Effects to Watch
Watch closely for the following side effects and notify your physician immediately should any of these develop:
•Abnormal heart rate, fluttering in the chest, weakness, faintness, dizziness or loss of consciousness (signs of a serious condition called "torsade de pointe or QT prolongation" in which irregular heartbeats occur)
•skin rash

Lab and Diagnostic Tests
If certain symptoms develop, ask your physician whether you need the following lab tests or other diagnostic tests (if you've not already had them):
•Monitor phosphorus, creatinine and liver function tests
•EKG - if abnormal heartbeats (rapid slow or irregular) develop
•creatinine clearance - check before starting treatment
•Monitor blood tests closely

http://doublecheckmd.com/EffectsDetail.do?dname=Atripla&sid=83796&eid=2089

Herniated Discs and Neuropathy

Yet another one of the possible causes of Neuropathy is discussed in this article from umr145.com (see link below). It is written by Dr. John Hayes jr, who has his own much publicised medical clinic and practice and has been featured before on this blog. If you have back problems, it is useful general information and certainly something to consider in discussions wih your doctor.

Why Herniated Discs Can Cause Neuropathy
December 2nd, 2011

Have you been diagnosed with a herniated disc?

If so, you probably have the usual symptoms:
Low backache
Numbness (if the disc is actually pressing on a nerve)
Leg pain

Those symptoms are no surprise.

But what may be a surprise are other symptoms:
Severe, sharp, electric shock-like, shooting pain
Deep burning or cold in the feet or legs
Numbness, tingling or weakness in the feet and legs that doesn’t go away
Radiating pain down the legs and into the feet
Muscle spasms and deep muscle pain

And those symptoms could be caused by neuropathy – a condition you probably never heard of until you developed a herniated disc.

So Why Does a Herniated Disc Cause Neuropathy?

A herniated disc alone may not cause you that much pain. The pain you experience is caused by the disc putting pressure on the spinal cord and on nerve roots. The location and intensity of the pain you experience depends on which nerves are affected by the disc and where it’s putting pressure.

Let’s say the disc is putting pressure on nerves that lead to your feet. You will probably feel pain and numbness in your feet. The longer the pressure is on the nerve, the more the nerve will be damaged. That nerve damage can lead to neuropathy in your feet.

The same applies to the nerves in any other part of the body. If your disc is putting pressure on nerves that affect that part of the body, you’re in danger of developing nerve damage and neuropathy wherever the nerves are affected.

If you have any of the neuropathy symptoms we listed above, you need to see your doctor, preferably your local neuropathy clinician, as soon as possible. The longer you let the nerve damage go untreated, the more likely the damage will be permanent.

Treatment Options

When you’re diagnosed with a herniated disc and develop neuropathy, the first goals of treatment are:
Pain relief – first and foremost
Address any weakness or numbness in your feet, legs and lower back
Prevention of additional injuries

Find a clinician with extensive experience in treating herniated discs and the accompanying neuropathy issues. Your local neuropathy specialist is an excellent place to start.

More than 90% of patients with herniated discs and neuropathy (if treated early on) will improve within 6 months without surgery. But you need to get in to the doctor and start treatment at the first sign of problems.

Once you get in to see your clinician, the treatment protocol will be adapted to address your particular issues. For the most part, you can expect:
Bed rest followed by increased, prescribed and controlled activity
Chiropractic manipulation to get the spine back into proper alignment and take pressure off the herniated disc and nerves
Treatment with the correct treatment system to open up nerve channels and stimulate nerve repair
Exercises to reduce your pain and strengthen the muscles in the back
Dietary counseling to address any other underlying medical issues you may have

Contacting a specialist today for information is the best course of treatment to make sure that you’re herniated disc and compressive neuropathy are treated properly and promptly. Save yourself years of back pain misery.

Neuropathy patients, doctors and physical therapists can find lots more about the neuropathy treatments and systems of Dr John Hayes Jr by going to http://neuropathydr.com. Peripheral neuropathy doctors, physical therapists and patients will find more information as well as post comments and questions at this site as well.

http://www.umr145.com/why-herniated-discs-can-cause-neuropathy.html

Why the Capsaicin Patch was Rejected for HIV/Neuropathy Sufferers

Today's interesting post from Poz.com (see link below) looks once again at why Qutenza was recently rejected for general release to HIV-related, neuropathy patients by the American FDA. Doctors can still prescribe it but you'll have to pay for it yourself - it won't be covered by insurance. This applies to the United States only and your own territory may have different rules but many countries follow the advice of the FDA. Another article discussing this question can be found by clicking here. Although many commentators are painting the FDA as the bad guys, it's not as clear cut as you may think.

Qutenza Still a Prescription for Pain
by Tim Horn

The FDA probably will not approve Qutenza as a treatment for HIV-associated peripheral neuropathy, but the novel pain patches can still be prescribed for anyone who might benefit from them. For many, however, it will ultimately come down to a question of cost and insurance reimbursement.

Few experts in the HIV community truly expected February 9, 2012, to end the way it did. Though there were lingering questions regarding the effectiveness of Qutenza, a novel patch to manage the debilitating symptoms of HIV-associated peripheral neuropathy, it was expected that the U.S. Food and Drug Administration’s Anesthetic and Analgesic Drug Products Advisory Committee would recommend the drug for approval. But alas, the committee unanimously voted against green-lighting what was on track to be the first treatment approved for one of the most common complications among people living with HIV.

Unfortunately, the agony of defeat won’t end with the FDA’s anticipated decision to follow its advisory committee’s decision. Without approval, the estimated 100,000-plus Americans living with painful HIV-associated peripheral neuropathy will continue lacking a new, potentially useful treatment to choose from.

Or will they?

Qutenza is commercially available in the United States, thus it can be prescribed and applied “off label” by health care providers, particularly for patients who either aren’t benefiting from or tolerating other unapproved and largely unproven therapies. But a challenge does remain: Getting health insurance providers to pay for patch and the procedure.

What Went Wrong?

Chili peppers and mustards have been used for centuries in topical balms to treat chronic pain. Only during the past few decades, however, have scientists figured out how capsaicin—the chemical that gives chilies their pungency—works as an analgesic: It depletes a neurochemical called substance P responsible for transmitting pain.

NeurogesX, based in San Mateo, California, has spent several years testing capsaicin in skin patches to treat a variety of chronic pain conditions. In May 2009, Qutenza, the company’s lead candidate designed to deliver a high concentration of capsaicin to affected areas, was approved for peripheral neuropathic pain in non-diabetic adults throughout Europe. Six months later, it was approved by the FDA to relieve the pain of post-herpetic neuralgia, a serious complication that can occur after a bout with shingles.

Qutenza’s proven usefulness for these indications pointed to tremendous potential for HIV-associated peripheral neuropathy. This was good news for people living with the condition—and for their health care providers, who for years have had very limited success using oral medications with significant side effects, notably anti-seizure medications and narcotic pain relievers. And according to an analysis published by the peer-reviewed online scientific journal PLoS One in 2010, Qutenza was one of only three treatments for peripheral neuropathy with proven efficacy in clinical trials. The others were smoked marijuana—a highly controlled substance and not widely available legally—and recombinant nerve growth factor, an expensive product with important side effects that isn’t approved for any indication.

Unfortunately, Qutenza’s effectiveness didn’t hold up under review by the FDA or its advisory committee. “The singular problem was the efficacy data in the clinical trials,” says David Simpson, MD, a professor of neurology at Mount Sinai School of Medicine in New York and a lead Qutenza researcher with a long history of scientific dedication and care for people living with HIV and various neurological problems. “Though there was some evidence of efficacy [in the first clinical trial], it was not by any means a home run. If a second study showed similar or better results, then I suspect there would have been approval.” But it was not meant to be, Simpson explains further, noting that the second study failed to meet the FDA-required standard of efficacy. And while post-study analyses “made the data look a little better,” Simpson adds, it wasn’t enough to carry Qutenza over the finish line.

“I was disappointed for sure,” Simpson says. “Many of the folks that have worked with this drug have treated patients clinically, and several of my patients gave testimonials at the hearing about how this drug helped them so much.”

FDA and advisory committee reviewers also seemed crestfallen. “Bob Rappaport [director of the FDA’s Division of Anesthesia, Analgesia and Addiction Products] said publicly that he was extremely disappointed in the result,” Simpson adds. “The advisory committee appeared that they very much wanted to approve this drug for HIV neuropathy, and they struggled with how to deal with the issues on the table.”

According to Simpson, it largely came down to precedents. “The FDA and the panel were very clear that they were concerned about setting a precedent, in that there needs to be sufficient efficacy for approval. Their concern was if they lowered the bar for this drug, it could set a precedent for any other drug coming down the pipeline that could argue, ‘Well you were easy on Qutenza, and that got approved with lower efficacy than usual, why can’t you do the same?’”

What’s Next?

The FDA has until March 7 to decide whether to approval NeurogesX’s supplemental new drug application for Qutenza for HIV-associated peripheral neuropathy—but the other shoe is fully expected to drop by that date. This will not, however, have any effect on the patch’s approval for post-herpetic neuralgia in the United States.

Qutenza can be prescribed for people living with HIV and peripheral neuropathy. “Off-label” prescription practices are common. After all, the various other agents used by people struggling with HIV-associated peripheral neuropathy are only approved for other indications.

In the HIV clinical trials, patches were applied for 30, 60 or 90 minutes, with the 30-minute application being the basis of NeurogesX’s approval request. The company also proposed that treatment “may be repeated every three months or as warranted by the return of pain.”

“I have used this drug off label for HIV neuropathy as well as for other neuropathic pain syndromes, and by no means does everyone respond,” Simpson says. But he adds, “there are a significant number of very good responders and some excellent responders like one of the patients that gave a testimonial at the [February 9 advisory committee] hearing. I believe his pain intensity level went from 9 to 2”—on a scale of 1 to 10—“and he said it changed his life; he couldn’t go out of the house before using it, and now he can go out of the house. So those kinds of dramatic effects are certainly compelling, and for patients with often little or no alternatives, certainly this is an option.”

The problem is cost. The wholesale price is set at $675 for a one-patch treatment kit and $1,350 for a two-patch treatment kit—which would probably be the minimum required, as HIV-associated peripheral neuropathy affects both feet and may require more than one patch on each foot for necessary coverage. And that doesn’t include the cost associated with application, which must be done by health care providers who rarely work for free.

Because of Qutenza’s questionable efficacy in clinical trials, compounded by its hefty price tag and associated application costs, Simpson explains that insurance reimbursement isn’t promising, but not a forgone conclusion. “Patients often have to pay out of pocket,” he says. “Some insurers are a bit more liberal and will approve it, but I think that without the FDA approval, it certainly will not help the rates of reimbursement.”

Public payers are, unfortunately, restrictive when it comes to medications and devices being prescribed off label. “Medicare,” Simpson offers as an example, “is almost uniformly disapproving any off-label use. My experience is they only approve for post-herpetic neuralgia and will reimburse for that.”

Medicaid reimbursement closely mimics Medicare coverage. As for AIDS Drug Assistance Programs (ADAPs), which are already stretched financially and unable to offer lifesaving antiretrovirals to all who need them, the lack of FDA approval will likely make it difficult for advocates to push for the Qutenza’s inclusion on ADAP formularies.

There is a glimmer of hope for those covered by private insurance policies. “Some commercial payers will occasionally approve the use of the drug in off-label use like HIV,” Simpson says.

A key for health care providers is knowing what to say to insurance companies during reimbursement pleas. “I can’t say I’m an authority on this, and I can only speak from my experience from writing letters and speaking to medical directors of insurance companies,” Simpson says in prefacing his experience in this regard. “I tell them the facts. First, that there is no FDA-approved drug for this affliction. Second, that the majority of studies and most of the medications that we use for other [forms of] neuropathic pain have shown negative results in HIV neuropathy. Third, there are at least some data to support efficacy in HIV neuropathy, particularly from C107 [the first Phase III clinical trial reviewed by the FDA]. Fourth, there is a very low risk of this drug. Finally, there are a significant number of patients who have responded very well.

“With that information,” Simpson concludes, “some of the insurance companies have been supportive and have reimbursed.”

http://www.poz.com/articles/hiv_neuropathy_qutenza_401_21975.shtml

Cancer Treatment and Neuropathy

Unfortunately, more and more people living with HIV are being confronted by various forms of cancer. This may be due to the fact that many more people are surviving and living longer with the virus and are therefore meeting diseases more associated with older patients. The point is that cancer treatment is also a well-known cause of neuropathy. The chemotherapy is the culprit though by no means everybody who undergoes chemo also contracts neuropathy as a result. That said, it will be difficult for doctors with an HIV and cancer patient to establish the cause of the nerve damage - it could be the virus itself, or the HIV medication, or the chemotherapy, or a host of other reasons.
Today's article from the NCI Cancer Bulletin of cancer.gov (see link below) is written by Brittany Moya del Pino (an article writer specialising in cancer discussions). It will be familiar to everybody already suffering from neuropathic problems but looks at it from a slightly different angle to those you may be used to on this blog.

Chemotherapy-induced Peripheral Neuropathy
by Brittany Moya del Pino

It usually starts in the hands and/or feet and creeps up the arms and legs. Sometimes it feels like a tingling or numbness. Other times, it’s more of a shooting and/or burning pain or sensitivity to temperature. It can include sharp, stabbing pain, and it can make it difficult to perform normal day-to-day tasks like buttoning a shirt, sorting coins in a purse, or walking. An estimated 30 to 40 percent of cancer patients treated with chemotherapy experience these symptoms, a condition called chemotherapy-induced peripheral neuropathy (CIPN).

CIPN is one of the most common reasons that cancer patients stop their treatment early. For some people, the symptoms can be mitigated by lowering the dose of chemotherapy or temporarily stopping it, which diminishes the pain within a few weeks. But, for other patients, the symptoms last beyond their chemotherapy for months, years, or even indefinitely.

“Peripheral neuropathy can be an incredibly debilitating side effect,” explained Dr. Ann O’Mara, head of NCI’s Palliative Care Program in the Division of Cancer Prevention. “We can’t predict who will come down with it or to what degree they will get it. So there are a lot of questions around this issue, in terms of preventing and treating it.”

Outside of clinical trials, CIPN symptoms are commonly managed in a manner similar to other types of nerve pain—that is, with a combination of physical therapy, complementary therapies such as massage and acupuncture, and medications that can include steroids, antidepressants, anti-epileptic drugs, and opioids for severe pain. But these therapies have not demonstrated true efficacy for CIPN, and virtually all of the drugs to treat peripheral neuropathy carry side effects of their own.

Life with Neuropathy

Cynthia Chauhan is a patient advocate who is very active in the cancer community. She participates with several boards and committees that advise NCI-sponsored clinical trial groups, including the North Central Cancer Treatment Group and the Southwest Oncology Group, and she is co-chair of the Patient Advocate Working Group for the Translational Breast Cancer Research Consortium. She is also very familiar with the burden of peripheral neuropathy and the shortcomings of current treatments.

A two-time cancer survivor, Ms. Chauhan lives with peripheral neuropathy that arose spontaneously—called idiopathic neuropathy—nearly 15 years ago. Her symptoms include shooting pains, fiery numbness, and tingling in her hands and feet, as well as a lack of sensitivity to temperatures. Her mother developed chronic CIPN during her treatment for stage IV ovarian cancer and, because of the pain, has terrible difficulty sleeping. “But without the drugs that caused her neuropathy, she would not have survived,” Ms. Chauhan said. “So she uses that knowledge to balance the negative aspects.

“I’m an optimist by nature,” Ms. Chauhan continued. “I like to focus on what I have, rather than what I don’t have, and I can still walk and use my hands—I’m an artist, so my hands are important to me. That I can still use them is very positive.”

She has tried several medications for her neuropathy, and all of the systemic drugs caused unbearable side effects. Today she manages her pain with Lidoderm patches and the practice of guided imagery and meditation, which she says function mostly as distractions for the pain. “Nothing ever stops it. It’s a 24-7 issue with me. I know that drugs work for some people, and if you can find effective medications under the care of a really knowledgeable physician, that’s great,” she said. “But more basic and translational research is critical for those of us who are living with the condition.”

Understanding the Pain

NCI’s Symptom Management and Health-related Quality of Life Steering Committee, of which Ms. Chauhan is a member, met in Rockville, MD, last year to discuss these issues. This steering committee is one of several that advise NCI as it works to improve the efficiency of clinical trials so that proposed treatment hypotheses can be translated more quickly into new screening, treatment, and prevention options for patients.

What actually causes CIPN, on the cellular and tissue level, is still largely a matter of speculation. There is evidence that nerves can become sensitized because the concentration of salts in the fluid surrounding them changes, or because the channels that use these salts to trigger nerve impulses become dysfunctional. These or other changes may actually damage the structure of nerves.

Because the underlying etiology may vary according to the chemotherapy agent and from patient to patient, more research with animal models is needed, in addition to clinical trials, to try to define the causes of CIPN and identify means to prevent or alleviate it, said Dr. Charles Loprinzi, the Regis Professor of Breast Cancer Research at the Mayo Clinic in Rochester, MN, who chaired the steering committee meeting.

“We need a multi-pronged approach,” he explained. “If we can better understand what causes CIPN in animals and which antidotes might be helpful for preventing and treating it, that doesn’t necessarily mean that [the antidotes] will be exactly the same in humans, but it will allow us the opportunity to screen promising compounds. Ones that successfully alleviate the symptom profiles in animals can be advanced to clinical trials in humans.”

Getting the Right Measures

“I’ve been very lucky not to develop this before now, actually…It’s likely just a side effect of the chemotherapy treatment that I’ve been receiving for the past 10 weeks (Taxol). And that’s why we’re taking a break from chemo this week,” Dr. Susan Niebur wrote in 2007 of her experience with peripheral neuropathy on her blog Toddler Planet, where she documents her experience as a mother and survivor of inflammatory breast cancer.

“Hopefully the week off will allow my system some time to recover and the pain to diminish. Already, my legs are responding more to me (no more wheelchair!) and I can feel my left foot. My right foot and leg, up to the knee, is still tingling and painful to the touch, but I hope that will also resolve in the next few days.” More than 2 years after finishing her chemotherapy, Dr. Niebur still has some residual neuropathy in her right foot and occasionally in her hand, but she wrote in an e-mail that it’s primarily a numbness now, “and a bother more than anything else.”

Patient-reported outcomes (PROs) during and after chemotherapy, such as those Dr. Niebur described, will be an important part of future research on CIPN. A tool that was developed by NCI and that is routinely used to record adverse effects from cancer treatment in clinical trials, the CTCAE, “is not adequate to help us fully understand this condition,” said Dr. Loprinzi. “As opposed to having a health care provider summarize the symptoms of a patient, it is much preferred to have patients more directly record their symptoms.”

PROs commonly include substantially more detailed and accurate information for a variety of symptoms. The steering committee identified several tools, including a 20-item patient questionnaire called the EORTC-QLQ-CIPN20, which appear to better capture this level of information.

Clinical Research Ahead

Several new agents have shown positive effects in pilot studies in patients with CIPN or neuropathy related to diabetes or HIV, and the steering committee has recommended that some of the more promising of these be pursued in larger placebo-controlled randomized clinical trials. Some of these trials are already enrolling patients, while others are still in the planning stages. More information about these trials can be found on NCI’s Web site.

For treating the pain associated with CIPN, agents that appear promising include the antidepressants duloxetine and venlafaxine, which are both serotonin/norepinephrine-reuptake inhibitors. Another promising agent is a topical compound of the muscle-relaxant baclofen, the antidepressant amitriptyline, and the analgesic ketamine.

For preventing the onset of CIPN, the committee recommended further clinical testing of intravenous calcium and magnesium, which reduced CIPN symptoms by approximately half compared with a placebo in one trial involving patients receiving oxaliplatin; a peptide called glutathione, which is thought to bind to heavy metals and has shown promise in small trials in patients who are treated with platinum chemotherapies; acetyl-L-carnitine, a substance that was effective in animal models and in patients with diabetes and HIV; and the antioxidant alpha-lipoic acid.

Pharmacogenomic studies will also, it is hoped, help guide the identification of patients who are more or less likely to develop CIPN. One such study is being planned at the Mayo Clinic to determine how a variation in genes that control taxane and carboplatin metabolism may affect a person’s risk of getting CIPN.

“I’m a relatively conservative person, in terms of how I practice medicine and research,” said Dr. Loprinzi. “But I’m excited about this area. We’re just starting to tap it. Over the next few years, as study results become apparent, I’m reasonably confident that one or two, or possibly more, of these agents will be shown to be beneficial for patients.”

http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/022310/page6