Monday, 31 August 2015

STDs And Neuropathy: Is There A Link?

Today's post from Dr. John Hayes' (see link below) looks at a possible cause of neuropathy that many people find not so easy to discuss but should nevertheless to be taken seriously and that is, the link between nerve damage and sexually transmitted diseases. If you're sexually active at any age and from any section of society, you have to face the possibility that one day you may come into contact with an std. That can be uncomfortable enough but realising that std's could affect your nervous system for life may just cause you to take a little more care with what you do and how you do it. This helpful article gives you a good overview of the risks and what you can do about it - worth a read.

STD & Neuropathy  
Posted by john on June 15, 2015

Let’s be honest, STD & Neuropathy are difficult to talk about.

Ignorance is NOT bliss, in fact it’s dangerous!


• Genital Herpes (or any one of the large number of herpes-simplex viruses)

• Gonorrhea

• Syphilis

• Chlamydia

• Hepatitis B and D

• HPV (Human papillomavirus infection)

Yes, we said one or more.

Because of the way sexually transmitted diseases (STD’s) are spread, it’s not uncommon to be infected with more than one STD through a single encounter. For example, about half of the people who are infected in a single sexual encounter with Chlamydia are also infected with gonorrhea at the same time.

If you’ve been diagnosed with an STD and you’re now experiencing

• Extreme fatigue

• Headaches

• Painful, swollen joints

• Swelling in your feet, legs or hands

• Pleurisy

You may have yet another symptom from your STD to worry about – any of these diseases can cause peripheral neuropathy.

If it does, the pain, swelling or even loss of sensation won’t go away on its own. And more than just causing pain, it can be deadly if the wrong nerves are affected.

How Does A Sexually Transmitted Disease Cause Peripheral Neuropathy?

Many of these STD are caused by viruses or bacteria. Viruses and bacteria can attack nerve tissue and severely damage sensory nerves. If those nerves are damaged, you’re going to feel the pain, quickly.

The virus that causes HIV, in particular, can cause extensive damage to the peripheral nerves. Often, the progression of the disease can actually be tracked according to the specific type of neuropathy the patient develops. Painful polyneuropathy affecting the feet and hands can be one of first clinical signs of HIV infection.

Any of these viral or bacterial disorders can cause indirect nerve damage. Those damaged nerves lead to peripheral neuropathy.

Exactly What Is Peripheral Neuropathy?

Peripheral neuropathy is a condition that develops when the peripheral nervous system is damaged by a condition like diabetes, cancer or a sexually transmitted disease. When these nerves are damaged, they no longer communicate properly and all the bodily functions they govern are disrupted.

Depending upon which nerves are damaged and the functions they serve, you can develop serious or even life threatening symptoms.

Why Should You Worry About Peripheral Neuropathy?

After all, you’ve already received a devastating diagnosis when you found out you had a sexually transmitted disease. Aside from the physical discomfort, as a responsible partner you have to alter how you handle the most intimate aspect of your life.

But you should worry about peripheral neuropathy because you could develop serious problems.

If your peripheral neuropathy affects the autonomic nervous system, you could develop

• Blood pressure problems

• Heart rate issues

• Bladder or bowel control issues

• Difficulty swallowing because your esophagus doesn’t function properly

• Bloating

• Heart burn

• Inability to feel sensation in your hands and feet

Beyond being uncomfortable, any of these conditions can cause serious health issues; some can even be fatal.

How Can You Protect Yourself?

If you suspect you have a sexually transmitted disease, get medical treatment immediately. If you’re sexually active and have more than one partner, you might want to be tested even if you don’t have any of the common STD symptoms. Often patients, especially women, are infected and have no symptoms. Getting tested and finding out early on if you’re infected will make it less likely that you’ll develop peripheral neuropathy and nerve damage.

If you know you have a sexually transmitted disease and you’ve developed any of the peripheral neuropathy symptoms we mentioned earlier, one of the smartest things you can do for yourself to head off potential problems is to consult a specialist who treats neuropathy and will recognize problems quickly and act to resolve them. A great place to start is with your local NeuropathyDR® clinician. Your NeuropathyDR® specialist follows a very specific protocol specifically designed to minimize nerve damage from peripheral neuropathy.

Contact us today for information on the best course of treatment to make sure that once your sexually transmitted disease is cured or under control, you won’t carry the burden of nerve damage from peripheral neuropathy.

For more information on coping with peripheral neuropathy, get your Free E-Book and subscription to the Weekly Ezine “Beating Neuropathy” at

Sunday, 30 August 2015

Should Older People Take Advantage Of Available Vaccines?

Today's post from (see link below) may seem slightly off-topic as far as this blog is concerned but actually, very little publicity is given to the fact that vaccinations can be very useful for adults with other conditions, as well as children. It's important to know which vaccinations are available and whether they're available in your area. As far as neuropathy patients are concerned, the so-called shingles vaccine is generally available to older people but possibly not publicised because of rising costs in health sectors - nevertheless, it's an important vaccine if you've had or are susceptible to shingles and/or neuropathy. Other vaccines mentioned here may also be of interest to people living with neuropathy - discuss it with your doctor.

Vaccines important for adults to lower exposure to diseases  
By ALYSSA HARVEY Aug 23, 2015

When many people think of immunizations, they automatically assume they are strictly for kids, but adults need them as well.

According to the U.S. Centers for Disease Control and Prevention, the more people who are vaccinated, the lower the possible risk of anyone’s exposure to vaccine-preventable diseases.

“The challenge is keeping up with vaccines that you’ve had. People forget it’s important to keep track,” said Julie Anderson, practice manager at the Glasser Clinic.

“That’s one of the advantages of having a family doctor because we keep track of that.”

Being immunized is important even as people grow older, said Dr. Jayashree Seshadri, an internist and employee health physician at The Medical Center.

“As you get older your immunity comes down and you’re susceptible to all kinds of illnesses,” she said.

Many vaccinations will provide a booster effect, Anderson said.

“The immunity doesn’t always last forever,” she said.

World travelers need to be immunized, Anderson said.

“If somebody’s traveling to an area of the world where they might have more or different diseases than we have here then you can get vaccinations for them,” she said.

A lot of people are asking for the whooping cough vaccine, Anderson said. The whooping cough immunization, which is part of the tetanus, diphtheria and pertussis vaccine, also known as Tdap, is recommended by the CDC to be gotten in one dose and then a booster dose every 10 years.

“Sometimes kids get whooping cough, but we have a mild infection and give it to kids who have not been immunized,” said Seshadri. “It’s very important when you’re around a newborn child you are immunized for the whooping cough.”

People also ask about the shingles vaccine, Anderson said.

“If you’ve had chicken pox as a child, you’re more prone to get shingles as an adult. (Vaccines) may prevent that. No vaccination is 100 percent guaranteed,” she said. “Check with your insurance carrier to see what vaccinations they cover. Medicare covers shingles vaccine in a pharmacy setting only, and that’s in an attempt to save costs. You have to have a prescription for that.”

The shingles vaccine is recommended for people 60 and older, but the U.S. Food and Drug Administration has approved them for ages 50 and older, Seshadri said.

“The only problem is that it is a live virus vaccine, so you have to talk to your doctor about whether or not to get it,” she said.

Fever and stress can cause the dormant chicken pox to become shingles. Complications from shingles include painful lesions and nerve pain called neuropathy that lasts after the lesions heal.

“The older you get, the opportunity of getting shingles is higher. The vaccine is designed to prevent the flare ups,” she said.

“Even if you get the flare ups they’re not as severe as they could be.”

Another vaccine elderly people over 65 should think about is for pneumonia, which can cause complications and death. Younger people with certain health conditions – including diabetes, heart failure, sickle cell disease and HIV – may also be recommended to be immunized. The vaccine is given in two doses, Seshadri said. One of them has been developed in the last two years.

“Even if you were vaccinated with the old vaccine, it’s important to think about the new vaccine,” she said.

It is vital to have flu shots every year, Seshadri and Anderson agreed.

“We know that flu is a contagious infection,” she said. “It can be mild or severe and sometimes causes death.”

Other vaccines Seshadri recommended include a tetanus shot every 10 years; the meningitis shot, particularly for those who will live in a college residence hall; and the human papillomavirus shot.

“We’re trying to catch them as kids, but if you are not vaccinated you can get them as adults,” she said of the human papillomavirus vaccine.

— For more information about adult vaccination schedules, visit the CDC website at

— Follow features reporter Alyssa Harvey on Twitter at or visit

Saturday, 29 August 2015

Living Longer With HIV And Neuropathy

Today's post from (see link below) looks at how living with HIV in 2015 can mean living a long and normal life, although there are problems that can crop up thanks to either the virus or the medication - (neuropathy is one of them). It's pretty much aimed at the success stories with HIV - those on regular treatment, who have achieved an undetectable status. However, many millions across the world do not live in this luxurious position and are denied treatment and exposed to vicious stigmas and our thoughts should always go out to them. Worth a read both for those living with HIV and those who are lucky enough not to.

HIV as You Get Older
By R. Morgan Griffin WebMD Feature Reviewed by Melinda Ratini, DO, MS

By 2013, almost 30 percent of all people with HIV were age 50 or over. This greying of the HIV population shows how well today’s HIV treatments can work.

HIV makes aging itself more complicated. But plenty of people have had HIV for years, even decades, and are doing well.

"These days, we fully expect that someone with HIV will live a long, healthy life," says Christine A. Wanke, MD, professor of medicine and director of the nutrition and infection unit at Tufts University School of Medicine. "But that means they have to plan ahead and adopt the healthy habits to stay that way, just like anyone without HIV." 

HIV and Aging: 5 Common Challenges

As you get older with HIV, you may face issues including:

1. Other conditions. Just like anybody, getting older means you're more likely to have health problems, and HIV seems to bump up the risk even more. "HIV accelerates the aging process and magnifies its effects," says John G. Bartlett, MD, professor at the Johns Hopkins School of Medicine and director of its AIDS service. So HIV may make you more likely to get heart disease, diabetes, cancer, osteoporosis, kidney problems, and other conditions.

2. Drug interactions. Since you’re already taking medicines for HIV, additional drugs for other conditions can increase the chance of interactions.

3. Loss of support. Some people become more isolated as they age. That happens more often to people with HIV, who may also be dealing with embarrassment about the condition or strained family relationships. If you're alone and disconnected, you're more likely to get depressed.

4. Changing roles. Like many people without HIV, you may be caring for your aging parents. That can add emotional and financial pressures.

5. Difficulty adjusting. "I talk to people with HIV who say, 'I didn't expect to live to middle age,'" says Brad Hare, MD, director of the HIV/AIDS clinic at San Francisco General Hospital. "'But now I'm middle-aged and I'm probably going to live another 30 years.'" Many people who got HIV long ago didn't plan for a long life, and adjusting can be a challenge. For instance, you might not have saved for a longer life.

7 Steps to Take

1. See an HIV expert. The more your health is complicated by age and other conditions, the more crucial it is to have an expert overseeing your HIV care.

2. Get good routine medical care. Specialty HIV care is not enough. Because your risks of other medical problems are higher, keep on top of your general health, says Hare. Get your annual physicals, keep tabs on your blood pressure, cholesterol, and other tests your doctor recommends.

3. Avoid drug interactions. Make certain every doctor you see knows about every medication and supplement you take, including prescription drugs, over-the-counter products, vitamins, and natural products. Doctors may adjust your medicines, dosages, or schedules to prevent interactions.

4. Improve your lifestyle. To enjoy life as you age, stay fit. Exercise regularly, and if you smoke, stop.

5. Eat a healthy diet. Go for lots of fruits and vegetables, lean proteins, whole grains, and healthy fats. "Eating a heart-healthy diet makes sense for everyone," says Bartlett. "But because people with HIV have higher risks of heart disease, it makes even more sense for them."

6. Seek support. Having a support system of family and friends is key. Make an effort to stay connected. If close friends or family have died or moved away, work on making new friends. You might also connect through a support group.

7. Get help. Call your local health department to learn about local resources for people with HIV, says Hare. Your local Council on Aging is a good place to start; it can point you toward programs and services that could help. A financial planner may also help you work on savings and expenses.

Friday, 28 August 2015

Alpha Lipoic Acid For Neuropathy And Aging!

Today's post from (see link below) looks at Alpha Lipoic Acid, a supplement that many people take in combination with other things to help relieve their neuropathy symptoms. It may seem a complex article but it does actually explain what Alpha Lipoic Acid does and how this benefit nerve cells (by stimulating the strength of the mitochondria (nerve energy cells). Not only this but it apparently has anti-aging properties too! This has been claimed before but most articles have avoided going into how this happens. This one attempts to explain the process. Apparently, by stimulating telomerase (protective bits at the end of chromosomes), it slows down the aging process. You'll need to read further to get more information but anti-aging is a definite added benefit for neuropathy sufferers who benefit from ALA supplementation. There is a problem however and that is that many people report no improvement whatsoever with ALA and it's not the cheapest supplement. Even in combination with Acetyl-L-Carnitine, it's very difficult to prove any suspected improvements. This may well be the fault of the supplement itself and difficulties with absorption. It's definitely worth while getting the best advice possible when buying anti-oxidant supplements such as these, so that they can be best absorbed into your system - otherwise, you may be wasting your hard-earned cash. Finally, as always with supplements - what works for one doesn't work for all and unfortunately it's often a question of trying things out over a reasonable period of time before moving on.

New anti-aging tricks from dietary supplement seen in mice
Woodruff Health Sciences Center | Aug. 20, 2015
Quinn Eastman

Shortened telomeres, the protective caps at the ends of chromosomes, are both a sign of aging and contribute to it.
Emory scientists have found that the dietary supplement alpha lipoic acid can stimulate telomerase, the enzyme that lengthens telomerase, in mouse blood vessels.

In human cells, shortened telomeres, the protective caps at the ends of chromosomes, are both a sign of aging and contribute to it. Scientists at Emory University School of Medicine have found that the dietary supplement alpha lipoic acid (ALA) can stimulate telomerase, the enzyme that lengthens telomeres, with positive effects in a mouse model of atherosclerosis.

The discovery highlights a potential avenue for the treatment for chronic diseases.

The results were published Thursday, August 20 in Cell Reports.

“Alpha-lipoic acid has an essential role in mitochondria, the energy-generating elements of the cell,” says senior author Wayne Alexander, MD, PhD, professor of medicine at Emory University School of Medicine. “It is widely available and has been called a ‘natural antioxidant’. Yet ALA’s effects in human clinical studies have been a mixed bag.”

ALA appears to exert its effects against atherosclerosis by spurring the smooth muscle cells that surround blood vessels to make PGC1 (peroxisome proliferator-activated receptor gamma co-activator 1)-alpha.

PGC1-alpha was already well known to scientists as controlling several aspects of how skeletal muscles respond to exercise. While the Emory researchers did not directly assess the effects of exercise in their experiments, their findings provide molecular clues to how exercise might slow the effects of aging or chronic disease in some cell types.

“The effects of chronic diseases such as atherosclerosis and diabetes on blood vessels can be traced back to telomere shortening,” Alexander says. “This means that treatments that can restore healthy telomeres have great potential.”

“What’s new here is that we show that PGC1-alpha is regulating telomerase, and that has real beneficial effects on cellular stress in a mouse model of atherosclerosis,” says Shiqin Xiong, PhD, instructor in the division of cardiology and first author of the paper.

Xiong and Alexander used a model of atherosclerosis where mice lacked the ApoE cholesterol processing gene and were fed a high-fat diet. In this model, mice also lacking PGC1-alpha have more advanced plaques in their blood vessels, but only in older animals, the authors show.

Consistent with the poorer state of their blood vessels, aortic cells from PGC1-alpha-disrupted mice had shorter telomeres and reduced telomerase activity. Having shortened telomeres led the smooth muscle cells to display more oxidative stress and damage to the rest of their DNA.

The authors show that introducing PGC1-alpha back into vascular smooth muscle cells lacking that gene with a gene-therapy adenovirus could restore telomerase activity and lengthen the cells’ telomeres.

Telomerase is off in most healthy cell types and only becomes turned on when cells proliferate. Because telomerase is active in cancer cells and enables their continued growth, researchers have been concerned that stimulating telomerase in all cells might encourage cancer growth or have other adverse effects.

As a way to boost PGC1-alpha in cells more conveniently, Xiong and Alexander turned to alpha lipoic acid or ALA. ALA is a sulfur-containing fatty acid used to treat diabetic neuropathy in Germany, and has previously been shown to combat atherosclerosis in animal models.

Treating isolated smooth muscle cells with ALA for one day could both stimulate PGC1-alpha and telomerase, the authors found. ALA’s effects on vascular smooth muscle cells could also be seen when it was injected into mice. Xiong and Alexander say they are now investigating the effects of ALA on other tissues in mice. They have not observed increased cancers in ALA-treated mice, but say more thorough investigation is needed to fully assess cancer risk.

“While ALA is present in many foods and its effects in animal models look promising, it may be problematic for clinical use because of its poor solubility, stability and bioavailability,” Xiong says. “We are designing new ways to formulate and deliver ALA-related compounds to resolve these issues.”

Co-authors include assistant professor Lu Hilenski, PhD, Nikolay Patrushev, MD and Farshad Forouzandeh, MD, PhD.

The research was supported by the National Heart, Lung and Blood Institute (HL60728) and as part of a Program of Excellence in Nanotechnology (HHSN268201000043C).

Thursday, 27 August 2015

Vast Numbers Of Americans Live With Daily Chronic Pain

Today's post from (see link below) looks at the huge numbers of Americans living with chronic pain on a daily basis. From this, you can also assume that similar proportions apply to many other first world regions and this highlights how ironic it is that nations with the best health services and facilities still have such a high proportion of chronic pain sufferers. A possible cause of this could be put down to lifestyle choices but most neuropathy patients will agree that their pain is a secondary result of another disease or condition. The article talks about the majority of these 25 million having back and joint pain but given that we know that 20 million Americans are living with neuropathy, they will all be experiencing some form of pain, or uncomfortable symptoms. Makes you wonder what the cross-over statistics really mean. Nevertheless, 25 million American chronic pain sufferers means 25 million people receiving medication of one sort or another and over a long period of time. The problem is obvious!

25 Million U.S. Adults Struggle With Daily Pain 
TUESDAY Aug. 18, 2015, 2015

 Pain is widespread in much of America, with more than 25 million adults -- 11 percent -- suffering on a daily basis, a new national survey reveals.

And approximately 14 million adults -- roughly 6.4 percent -- experience severe pain, which can be associated with poorer health and disability, researchers found.

Other national studies of chronic pain have yielded similar results, said study author Richard Nahin, an epidemiologist with the National Center for Complementary and Integrative Health at the U.S. National Institutes of Health (NIH).

"What makes this study unique is that I also looked at how often adults have mild pain," he said.

Nahin found that about 54 million adults -- nearly one-quarter -- reported "mild," but not incapacitating, pain.

Whether pain is increasing nationally is difficult to say, Nahin said. But the good news is that roughly half of those living with severe pain indicated in the survey that they were nevertheless in good or excellent physical health overall.

And even better news: The poll found that 44 percent of American adults say their lives are pain-free.

The estimates are based on the responses of nearly 9,000 adults who took part in the 2012 National Health Interview Survey. The poll is conducted annually by the U.S. Centers for Disease Control and Prevention.

The NIH says more Americans are affected by pain overall than are touched by diabetes, heart disease and cancer combined. Also, chronic pain is the leading cause for long-term disability.

Nahin said joint pain and back pain are the most common sources of discomfort.

"About one-third of all adults have joint pain in a given year, and a bit more than a quarter of all adults have back pain," he said.

For the study, published in the August issue of the Journal of Pain, Nahin asked survey participants about the frequency and intensity of pain experienced in the preceding three months. He coded reported pain into five categories of severity, based on persistence and the degree to which it was "bothersome."

About one in 10 adults experiences "a lot" of pain, researchers found, and nearly 56 percent reported some pain in the preceding three months.

Overall, the researchers found that whites, women, and the elderly were more likely than others to report relatively severe pain.

The survey also found that adults experiencing the most severe levels of pain are likely to be more disabled, in worse overall health, and in need of more health care, compared with people dealing with relatively mild pain.

For those looking to mitigate chronic pain, Nahin said various health approaches can be tried with -- or in place of -- prescription painkillers. Many people turn to yoga, massage and meditation to relieve pain, for example.

"Evidence-based clinical practice guidelines from the American College of Physicians and the American Pain Society found good evidence that cognitive behavioral therapy, exercise, spinal manipulation and interdisciplinary rehabilitation are all moderately effective for chronic or subacute [lasting more than four weeks] low back pain," Nahin noted.

In addition, American College of Rheumatology guidelines advocate tai chi, acupuncture and/or walking aids for knee arthritis, he said.

People in search of a pain plan will often need to mix it up, said Dr. Edward Michna, director of the Pain Trials Center at Brigham and Women's Hospital in Boston, and a board member of the American Pain Society.

"Certainly not all pain requires opioids," Michna said, referring to narcotic medications such as hydrocodone (Vicodin) and oxycodone (OxyContin, Percocet).

"They have a role to play, of course," he added. "But what is needed is an individualization of care and a multidisciplinary approach that might include physical therapy, mind-body therapy, alternative medicines of various kinds, and other types of nonnarcotic medications."

The best treatment "will usually be a combination of these things. There is no one right answer," said Michna, who was not involved in the study.

More information
There's more on pain management at the American Chronic Pain Association.

Posted: August 2015

Wednesday, 26 August 2015

Got Neuropathy? Will It Get Better Or Worse?

Today's post from (see link below) asks the question we all want to know and provides the answer, that none of us, including the doctors, know whether our nerve damage will get worse or not. They also don't know if it will improve, yet for some people it does. Some patients seem to get better only for the symptoms to return some time later, maybe in a different place and maybe much worse than before. It's that sort of disease unfortunately and at the moment there's not a damn thing we can do about it except hope we will find the right medication for us that will reduce the symptoms and make life bearable. Of course doctors can predict outcomes but not to any certainty and it is often left to the patient to negotiate his or her way through the minefield of neuropathy medications and treatments. That's character building!

Will My Neuropathy Get Worse?
By LtCol Eugene B Richardson, USA (Retired) BA, MDiv, EdM, MS28 

One issue neuropathy patient’s face is the fear that their neuropathy will grow progressively worse. Neurologists call this a progressive polyneuropathy. The truth: no one really knows if your neuropathy will worsen, stay the same or disappear. A neurologist shared that this may have more to do with the underlying cause of the neuropathy, genetics, and heaven only knows, issues.

I speak of this very fear in chapter twelve, Focus, in the DVD “Coping with Chronic Neuropathy”, and if you have not viewed this chapter, I suggest that you do so. The viewing will provide a better perspective.

Neuropathy patient fears are often increased by the coming and going (remitting and relapsing) of neuropathy symptoms. These patterns are a medically confirmed fact and also occur in many other chronic illnesses. Better recognized are the same patterns for some forms of MS (Multiple Sclerosis)!

Neurologists confirm that there are acute neuropathies that come on suddenly and then the symptoms disappear. In other neuropathies symptoms occur, disappear and then return at the same level. Other neuropathies occur, disappear and then return at increased levels and in more places of the body. Others come, go and then go away for years only to return with a vengeance!

The chronic neuropathies (affect one set of nerves) and polyneuropathies (affect many nerves), which increase for years are often referred to as progressive polyneuropathies. The mystery is increased as there seems to be no rhyme or reason for these patterns. The only thing I noticed is that when I increased activity, I have increased burning, pain or other symptoms and I neurologist tell me that this is due to making damaged nerves work.

For years between the emotional highs when my symptoms remitted (“Hurrah, they’re gone!”) and the emotional lows when they relapsed (“Oh no, they’re back!”), I was tempted to worry that my symptoms were going to worsen and guess what, they did! But one has to ask the question, did the energy spent on worry change anything? No! What I re-discovered was what I learned in Sunday school. It was better to spend my time and energy finding a doctor who was trained (neuromuscular neurologist) in the clinical approaches to neuropathy then to waste energy on worry. I needed a doctor, not worry, to focus on my symptoms. I needed a doctor working with me as a partner, while treating the symptoms and looking for the TYPE and/or CAUSE. Why finding the type of neuropathy important? Because as Dr. Latov in his book tells us, this can often point in the direction of a cause! I needed a medical Sherlock Holmes, not time worrying about what might happen.

This approach maintained a focus on self empowerment by learning all I could, while prodding the doctors with questions that helped them think and act. The most important question for you is not, will my neuropathy get worse, but what is the type of neuropathy and/or the underlying cause? Spend your energy looking for the type and/or cause, as no one knows if your neuropathy will worsen or not.

I know that for so many of you neuropathy has been a progressive illness which worsened over the years. Conversely, my progressive polyneuropathy has not killed me, for my neuropathy symptoms began at age 31 and I am now 76. Thirty-five years into the symptoms with a million denials with a diagnosis from mentally ill to idiopathic neuropathy. I was given one drug which drove me to talk backwards and then another that reduced pain by 80%. Five years later with the miracle of IVIg I am able to keep breathing and the chest muscle spasms stopped while reducing other mind numbing symptoms. This took many doctors, lots of research and knowledge, while asking good questions and giving doctors documents from experts. It may have been fear and anger which drove me forward, but it was these focused actions that brought help, not dwelling on my fears!

It is important to know which issue is important as you set goals for getting help. It is important to focus your energy on learning, getting help with symptoms and finding the cause and solutions for the diagnosed illness. I do not mean idiopathic neuropathy (of unknown cause). It is very difficult to find a solution, other than for symptoms, when the neuropathy is of unknown cause. Help the doctor think and pushing the system to do the testing that is now available. Click here to read about my opinion on Idiopathic Neuropathy.

Tests that are available will allow the doctor to know if the neuropathy is large or small fiber, motor, sensory or autonomic, axonal, immune-mediated, demyelinating or inflammatory and these clues can lead to a possible identification of the type and/or cause that is more helpful than idiopathic.

RESOURCE: Read Dr. Scott Berman’s book, as this book may provide insight on these issues. Click here to view the recommended Books On Neuropathy. Dr. Berman has untreatable CIDP (chronic inflammatory demyelinating polyneuropathy) and his book speaks to all neuropathy patients as one who has been in our shoes with many neuropathies. Dr. Berman empowers us to face creatively the emotional issues we ALL face in chronic illness.

Tuesday, 25 August 2015

Missing Link Found Between Brain And Immune System

Today's post from (see link below) centres around the discovery that the brain is physically linked to the immune system after all. Previously, the lymphatic system had shown no traces of vessels directly linked to the brain and now they've been found. So what does this mean to neuropathy sufferers? It has long been known that many forms of neuropathy have an immune system response built in and that the patient's immune system is attacked when he or she has nerve damage. Mapping this, or tracing to the source in the past has been impossible and consequently guesswork has happened more often that would be wished for. Now scientists can follow an immune system response to the brain and back and make predictions based on facts rather than suppositions. This may lead to new treatments that are far better targeted at the immune problem than the all-encompassing drugs we have now. It may be difficult to understand but scientists are jumping up and down in excitement, so we have to trust that this is a major breakthrough.

Missing link found between brain and immune system

In a discovery that could overturn decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist.

That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer's disease to multiple sclerosis.

"Instead of asking, 'How do we study the immune response of the brain?' 'Why do multiple sclerosis patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG).

"It changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can't be studied. But now we can ask mechanistic questions.

"We believe that for every neurological disease that has an immune component to it, these vessels may play a major role. Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component."

Kevin Lee, PhD, chairman of the UVA Department of Neuroscience, described his reaction to the discovery by Kipnis' lab: "The first time these guys showed me the basic result, I just said one sentence: 'They'll have to change the textbooks.' There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation - and they've done many studies since then to bolster the finding - that it will fundamentally change the way people look at the central nervous system's relationship with the immune system."

The discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis' lab. The vessels were detected after Louveau developed a method to mount a mouse's meninges - the membranes covering the brain - on a single slide so that they could be examined as a whole. "It was fairly easy, actually," he said. "There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn't have worked."

After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. The soft-spoken Louveau recalled the moment: "I called Jony [Kipnis] to the microscope and I said, 'I think we have something.'" As to how the brain's lymphatic vessels managed to escape notice all this time, Kipnis described them as "very well hidden" and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. "It's so close to the blood vessel, you just miss it," he said. "If you don't know what you're after, you just miss it."

"Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris," Kipnis noted. Harris, a PhD, is an assistant professor of neuroscience and a member of the BIG center. Kipnis also saluted the "phenomenal" surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.

The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer's disease. "In Alzheimer's, there are accumulations of big protein chunks in the brain," Kipnis said. "We think they may be accumulating in the brain because they're not being efficiently removed by these vessels." He noted that the vessels look different with age, so the role they play in aging is another avenue to explore. And there's an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.

Source: Medical Xpress © Medical Xpress 2011-2015, Science X network (02/06/15)

Monday, 24 August 2015

What Is Non-Diabetic Neuropathy?

Today's short post from (see link below) is slightly strange in that it suggests that diabetic and non-diabetic neuropathy symptoms are different, when in fact they are pretty much the same. So many sites and articles concentrate on neuropathy as a result of diabetes, mainly because diabetes is by far the commonest cause of neuropathy. However, this can cause confusion for many people with non-diabetic-related neuropathy who ignore information if it has diabetes in the title. The difference is in the cause, not the effects and that is so for all neuropathies caused by something else. The point is, when you have neuropathy, you're sharing symptoms pretty much common to most people in the same boat - the cause is history, the treatment from that point on is vital.

Non-Diabetic Neuropathy Symptoms 
Last Updated: Aug 03, 2015 | By August McLaughlin

Neuropathies may cause sensory, autonomic and motor skill symptoms. 


Neuropathy, also known as peripheral neuropathy, is a condition that causes numbness, pain, tingling and weakness, usually in the hands and feet. It may occur episodically or progress gradually over years. According to the Neuropathy Association (NA), 30 percent of cases evolve from diabetes, 30 percent from unknown causes and 40 percent from infections, autoimmune disorders, genetic factors, nutrient imbalances, tumors or toxins. Symptoms of neuropathy vary depending on type of neuropathy and which nerves are affected.

Sensory Symptoms

Neuropathy causes damage to fibers that affect physical sensation, which causes nerve pain, tingling and numbness. Sensory damage may reduce a person's ability to determine the position of his joints and suffer from poor coordination. According to the University of Maryland Medical Center (UMMC), sensation symptoms frequently start within the feet and gradually progress toward the body's center as neuropathy worsens. Though sensory symptoms are common among diabetes-related neuropathy, it affects other forms as well.

Movement Problems

When neuropathy causes damage to fibers that affect a person's muscles, it can lead to physical weakness, loss of dexterity and reduced muscle mass. Muscle cramping or twitching, trouble swallowing or breathing, paralysis of affected body parts and reduced muscle control may also occur. According to the UMMC, these symptoms often lead to tripping, resultant injuries and difficulty executing tasks that require dexterity, such as buttoning a shirt, writing and opening jars and doors. Reduced nerve function in the hands may cause people to drop objects frequently. When leg muscles are weakened, people may struggle to run or walk or observe a sense of "heaviness" in the legs. Normally simple tasks such as climbing stairs may become challenging and lead to frustration and muscle cramps. 

Autonomic Symptoms

Neuropathy may also affect that autonomic nerves that contribute to involuntary functions, such as heartbeat, digestive processes, blood pressure and organ function. When this occurs, numerous symptoms may evolve, such as blurry vision, constipation or diarrhea, inability or reduced ability to sweat, abdominal bloating and difficulty during urination. According to the UMMC, fainting or dizziness upon standing may indicate a drop in blood pressure caused by autonomic neuropathy symptoms. People with neuropathy may become sensitive to heat during physical exertion, such as exercise. When the digestive system is affected, nausea or vomiting may occur after eating. Impotence in males and unintentional weight loss may also stem from these symptoms.

Sunday, 23 August 2015

Marijuana Chewing Gum May Be An Option For Neuropathic Pain

Today's short post from (see link below) announces the arrival of cannabis chewing gum as an alternative to smoked or vaporised cannabis for pain relief. if and when it is apporved and developed to the right strengths for slow release cannabis, it could prove to be a very valuable option for people who can't smoke cannabis, or inhale it via various mechanisms. Chewing gum may be an acceptable means of delivering cannabinoids without the unpleasantness normally associated with smoking. Ironically, it can be equated to nicotine chewing gum which is used to help people stop smoking. This short article is aimed at MS sufferers but it applies to all people who suffer chronic nerve pain and other symptoms and could be an important development in the field of pain control.
MS patients may someday find relief in marijuana chewing gum
By Kathleen Burke, MarketWatch 8-17-15 11:06

Marijuana-infused gum enters clinical trials

Patients can smoke it, eat it and soon, they may be able to chew it.

Cannabis-focused biotech company AXIM Biotechnologies (AXIM) last week said it launched clinical trials on humans for medical cannabis chewing gum as a treatment for multiple sclerosis. The gum, MedChew RX, contains 5 milligrams of cannabidiol -- a non-psychoactive component of cannabis -- and 5 milligrams of THC -- a psychoactive cannabinoid.

Medical marijuana chewing gum "should allow for predictable and controlled release of the active ingredients," George Anastassov, chief executive of AXIM, said in a statement. It should not be socially stigmatizing, should have a pleasant taste and consistency and no undesirable side effects, he added. "Chewing gum meets all these criteria."

AXIM already has a cannabinoid chewing gum product, known as CanChew, on the market, however it does not contain THC and does not offer any medical claims.

The psychoactive component of THC is an effective way to treat patients with degenerative diseases, in addition to the medicinal properties of cannabidiol, which can be used to treat neurological conditions such as epilepsy. Additionally, the act of chewing helps preserve cognition and memory, as well as promotes overall oral health, Anastassov told MarketWatch.

While the current trials of the gum are only for MS patients, Anastassov says Axim hopes to expand the range of conditions it can be prescribed for.

"For multiple sclerosis, the market for treatment is quite large," Anastassov says. "Eventually, we will try to enlarge the conditions for this medication, such as pain." (More than 2.3 million people are affected by MS globally, according to the National Multiple Sclerosis Society.)

He says pain is one of the most predominant symptoms patients of a wide variety of diseases including MS suffer from globally, and there have been few game-changing drugs in the pharmaceutical market to help treat it.

There is no cure for MS, but current treatments work to speed recovery from attacks, slow the disease's progression and manage symptoms, according to the Mayo Clinic. The most common treatments used to manage symptoms are physical therapy, muscle relaxants and medications to reduce fatigue, depression and pain.

The Phase 1 trial of the gum is slated to begin in the second quarter of 2016. Though medical marijuana is legal in 23 states and the District of Columbia, it is classified on the federal level as a schedule I drug, which gives it the same illegal status as heroin and LSD and is considered to have no accepted medical use.

While the FDA has yet to approve any product containing cannabis, it has approved Marinol -- which contains dronabinol, a synthesized form of THC -- for anorexia, chemotherapy and AIDS patients. The FDA's website says it will continue to assess the effectiveness of marijuana for medical use, and will work with companies on medical cannabis research.

If the gum is approved by the FDA, it could be available in all 50 states, even if they have not legalized medical marijuana. "That's why we're going through the FDA," Anastassov says. "There's no ambiguity as to where it's legal."

-Kathleen Burke; 415-439-6400;

Saturday, 22 August 2015

You've Got Neuropathy But Why Do The Tests Show Nothing?

Today's post from (see link below) is another well-written post by Lt.Col. Richardson, in which he quite rightly takes doctors and neurologists to task for their often summary dismissal of neuropathy patients as 'idiopathic' and thus 'unproved'. What do you feel when a doctor says 'the tests all came back normal'? The implication is that either you're exaggerating, or lying, or somehow wasting their time, especially if you're then sent home, or pointed somewhere else on the medical spectrum. These are neurologists and other qualified medical professionals who often say this and they should know better. A patient's story and symptoms should be enough to establish nerve damage; the tests can only point to the extent of the damage and hint at the cause but should never be regarded as a definitive diagnosis upon which further treatment depends. As the Lt. Colonel points out in his ten facts you should be aware of; there is still a need for much greater research and much better education for the medical professionals themselves - insurances, jobs, benefits and people's lives depend on it! Worth a read!

I Have Neuropathy – So Why Are My Tests Normal?
By LtCol Eugene B Richardson, USA (Retired) BA, MDiv, EdM, 

Being a patient with CIDP/Autonomic PN for over 45 years due to exposure to Agent Orange in Vietnam, this is a subject with which I have a lot of hard earned experience.

So, let me be clear. The over two hundred doctors I saw for my symptoms from 1969 to 2003, including those noted below are highly trained medical experts. So what was the problem with getting an accurate diagnosis and treatment during those decades?

For over three decades, upon complaining of symptoms since 1969, I was told by the doctors, “All tests are normal”. They implied, and I assumed this meant, I did not have anything wrong or did not have neuropathy.

One neurologist in 1979 did hedge his opinion stating “probably not neurological.” The word ‘probably’ without providing a medical opinion as to what may be wrong was not very helpful. So what was the problem?

In 1983, fifteen years after the horrific symptoms began; I became upset when the doctor said to me, “Why do you want something to be wrong?” Now I knew something was wrong and I wanted it fixed? Of course the doctor meant it was a mental problem and I concluded at the time I surely must be crazy. So what was the problem?

In 1999 after a doctor finally told me I had idiopathic peripheral neuropathy, I was sent to an expert neurologist who tested my reflexes and with compression on the leg he managed to get reflexes. Based on his special reflex test, he dismissed the diagnosis of idiopathic peripheral neuropathy, stating “patient has reflexes upon compression – patient is claiming to have something he does not have”, almost destroying what remained of my mental stability!

Not until years later did I understand that even the diagnosis that included the word ‘idiopathic’ was part of the problem involving the lack of clinical medical training in understanding the tests and what they do mean or do not mean or measure!

A neurologist in 2005 seven days after receiving gamma globulin for my diagnosed condition and at the peak of the infusions positive documented effect on my neurological illness, dismissed the diagnosis stating, “I cannot find any reasons for patients symptoms.”

Today, we have come a long way in the increase in information on Neuropathy, the increased understanding of neuropathic pain, and the skill of physicians to interpret the tests that are available. But it still takes a highly trained neuromuscular neurologist with special training in this area to diagnose and treat neuropathy. To understand the complexity of getting a diagnosis, perhaps read what Waden Emery III, MD Clinical Neurologist states about What is Neuropathy?

So the question I asked was – if you have neuropathy – so why are tests normal? Thank heavens that because of the hard work of many, we can answer that question clearly.

Here are TEN CURRENT FACTS every neuropathy patient must know!

FIRST, there are no objective tests for diagnosis of neuropathy and early in the illness; the doctor may have only your medical history and a subjective description of your symptoms. The current tests measure any damage to the large or small fibers, axon or myelin, and whether it is a single neuropathy or a polyneuropathy (affecting many nerves).

SECOND, neurology does not have the tools to diagnose peripheral neuropathy objectively, UNTIL damage can be measured or its affects are seen on the body (i.e. deformed feet in CMT, GBS patient can’t breathe, MMN patient can’t move an arm, or multiple issues with digestion, urination, sweating, etc.- See Dr. Norman Latov’s book for definition of acronyms.)

THIRD, peripheral neuropathy is diagnosed by ruling out possible causes of your symptoms. The tests done only look for that cause, not whether you have neuropathy or not, thus many tests are normal! Yet the type of neuropathy, which can often point toward a cause can be determined by these tests and the neurologist must indicate the type, not idiopathic which is not helpful. The failure to find a cause from the tests conducted rules out that cause, not your neuropathy.

FOURTH, testing is done to determine any measurable damage to the nerve or covering of the nerve and perhaps point to the possible type of neuropathy, not whether you have peripheral neuropathy or not.

In 2015 more doctors are understanding the need for the skin biopsy if the EMG or Nerve Conduct Tests do not show damage to the large fibers. More doctors are understanding the value of the spinal tap in diagnosis of an immune mediated neuropathy or the value of the genetic testing that will provide the patient with important affirmation!

FIFTH, most objective tests only determine the extent of damage to the peripheral nervous system, but if you have no or little damage this does not rule out a peripheral neuropathy, as it many chronic progressive neuropathies it can take years before damage can be measured.

SIXTH, the medical literature, including statements by Dr. Norman Latov of Columbia University, note that in Peripheral Neuropathy, reflexes may be absent or diminished, but not always, so alone this is not a standard for diagnosis of or dismissal of neuropathy.

SEVENTH, symptoms including painful skin on touching or sensations of pin prick, or sensitivity to hot or cold, as well as other symptoms, remit and relapse in patients with peripheral neuropathy and thus are only reliable for diagnosis when correlated with ALL available information including the patient’s medical history.

EIGHTH, treatment by gamma globulin does reduce the symptoms of immune-mediated neuropathies and this positive response confirms the diagnosis, thus a physician should not dismiss an existing diagnosis based on the absence of the symptoms following the infusion of gamma globulin or other effective treatments.

NINTH, as noted by Russell Chin, MD, Neurologist in New York City, we need better clinical training for doctors including neurologists both in the medical schools and updated clinical training for practicing physicians. The clinical training of all neurologists and physicals working with neuropathy patients must be a top priority for medical and neuropathy organizations.

TENTH, we desperately need MORE neuropathy research seeking better diagnostic tools for doctors, more treatment options, and improved approaches to treatment of chronic neuropathic pain.

Pam Shlemon, President of the Foundation for Peripheral Neuropathy is working with researchers to deal with the problem that very few research projects even make it to phase 3 trials and the question is why? Hopefully, her team will discover some answers and provide better direction for research.

An early diagnosis of the cause of a neuropathy and approaches to treatment are critical for many patients to prevent serious disability or worse from damage to the peripheral nervous system.

One could call these the TEN COMMANDMENTS for diagnosis of peripheral neuropathy!

Friday, 21 August 2015

Alternative Treatments For Neuropathy: Dismiss Or Embrace?

Today's post from (see link below) is not directly related to neuropathy but has definite relevance for people living with neuropathic problems. Because of a lack of definitive and universally effective treatments for neuropathy, many people are forced to seek relief in the alternative medicinal circuit. Referring to it as that, immediately implies that it's something less than the standard range of treatments but that's not universally true. This article looks at alternative medicine and asks the question, how much of what we think about alternative therapies is based on preconceptions and labels? The fact is, alternative medicine just isn't going away and that suggests that enough people gain considerable benefit from it to make it a valid option, especially for desperate people as neuropathy patients frequently are.
Labels Like ‘Alternative Medicine’ Don’t Matter. The Science Does.
Aaron E. Carroll AUG. 10, 2015

The University of Toronto recently stirred up a bit of controversy by offering an uncritical class on “Alternative Medicine.” A variety of bloggers and journalists brought up many valid concerns about the curriculum, but there is a much larger problem: No one is sure how best to teach that subject.

The dichotomy, however, between alternative and traditional medicine, or between Eastern and Western medicine, is a false one. We would be much better off if we could reframe the issue.

People often think of Eastern or alternative medicine as more “natural.” Many feel that Western medicine is built around technology and products produced in a lab. They’re not entirely wrong. Many of the gains that have been made in traditional medicine have been the result of innovation in laboratories.
 But that doesn’t mean that everything doctors are taught in medical school involves a drug or device. I talk to patients all the time about diet and exercise. I don’t do this because there’s a company making money off it. I do it because both of these things have proved to be important for health.

Nor do all medications get cooked up in a lab. We recommend folic acid, which is a B Vitamin, for pregnant women because research has shown that it reduces the risk of major birth defects in newborns. We all know that adequate intake of vitamin C prevents scurvy and that vitamin D prevents rickets.

None of these things are controversial to physicians. We recommend them all the time. That’s not because they were developed in the Western Hemisphere. It’s because they have been subjected to the rigor of scientific investigation — and found to have merit.

There are many other forms of nontechnological medicine that have the weight of scrutiny behind them. In a meta-analysis published just a few years ago, researchers looked at all the accumulated randomized controlled trials examining how acupuncture fared in treating people with chronic pain. They found that not only did acupuncture work better than no-acupuncture control groups, but there were also significant differences between acupuncture and sham acupuncture. This suggests that not all of the benefits are placebo effects.

People have been treating many mental health problems with therapy for years. Full disclosure: I’m one who has been treated. I’ve never taken any of the long-term psychotropic drugs, and many patients prefer not to if possible. Austin Frakt, my Upshot co-contributor, wrote recently about the evidence supporting cognitive behavioral therapy for insomnia, as well as for a host of other health problems. Even mindfulness, or meditation, has been studied extensively, and found to be pretty effective in treating anxiety and mood problems. I’ve been convinced enough by this evidence to try meditation myself.

I would argue that all the therapies I mention here aren’t considered complementary therapies — they’re often just considered therapies. That’s because they’ve been studied, and they’ve proved to work. Too often, though, those who consider themselves supporters of alternative medicine disdain the idea that any of their treatments need to be studied. They make an appeal to the fact that their medicine is more natural; has been used for long periods of time; or has the support of many people in other cultures.

Of course, not long ago, all therapies could be described in this way. The application of modern science allowed us to devise and conduct trials that could prove or disprove a treatment’s efficacy or harm. Many of the drugs we use today had natural origins. Digitalis comes from foxglove, quinine from cinchona bark, penicillin from bread mold and aspirin from willow tree bark. Conventional medicine may have improved our ability to purify these substances, but it acknowledges that many natural therapies hold value.

Yet science rejects many forms of complementary medicine as ineffective. Just a few months ago, the National Health and Medical Research Council of Australia released a report in which it fully reviewed 225 studies of homeopathy, the practice of treating sick people with small amounts of substances that cause similar symptoms in healthy people. They found no well-designed studies that found it to outperform a placebo or function as well as any conventionally approved therapies. Their conclusions echoed a previous report from Britain, and those found in many Cochrane systematic reviews

My friends who believe in homeopathy don’t really care.

Those who favor conventional medicine, though, can be just as blinded. Too often, when confronted with evidence that advanced technology might not be providing benefits, the medical community refuses to change its behavior. My Upshot articles are littered with examples of this, including potentially too-widespread mammography screening, advanced life support and many surgical procedures. Supporters of Western medicine are often blind to their own prejudices.

Butterbur, a plant extract, has been found in medical studies to be as effective as antihistamines in treating allergic rhinitis, without the sedating side effects conventional drugs often have. Horse chestnut seed extract appears to be safe and effective in the short-term treatment of chronic venous insufficiency. Peppermint oil can be used to relieve the symptoms of irritable bowel syndrome. I know of few physicians who promote these therapies as often as they do prescription or over-the-counter drugs. Granted, that could be because it’s potentially hard to be sure of supplements you’re buying, but there are ways to overcome those problems.

In 1998, The Journal of the American Medical Association published a theme issue on alternative medicine for common chronic medical conditions. The randomized controlled trials within it offered evidence that spinal manipulation did not improve tension-type headaches, that acupuncture and acupressure didn’t reduce pain caused by H.I.V.-related peripheral neuropathy and that the supplement Garcinia cambogia did not help with weight loss. However, the same issue contained studies that showed that yoga-based interventions improved carpal tunnel syndrome more than wrist splinting, that the Chinese practice of moxibustion significantly increased fetal activity and fixed breech presentations before delivery, and that Chinese herbal medicine appeared to improve symptoms in some patients with irritable bowel syndrome. Although some of this research has been continued, to my knowledge neither side of medicine has changed practices or beliefs much based on this work.

In an accompanying editorial, Phil Fontanarosa and George Lundberg, two of JAMA’s editors, wrote: “There is no alternative medicine. There is only scientifically proven, evidence-based medicine supported by solid data or unproven medicine, for which scientific evidence is lacking.”

I’d change this only by adding, “There is no conventional medicine.”

Correction: August 10, 2015
An earlier version of this article misstated the surname of an editor at JAMA. He is George Lundberg, not Lungberg.


Aaron E. Carroll is a professor of pediatrics at Indiana University School of Medicine. He blogs on health research and policy at The Incidental Economist, and you can follow him on Twitter at @aaronecarroll.

Thursday, 20 August 2015

The Pros And Cons Of Medical Marijuana

Today's post from (see link below) looks at the ups and downs in the journey of acceptance for medical marijuana. This is what we need folks! Articles that look objectively at the facts and refer to the latest findings, especially regarding socially sensitive subjects like medical marijuana. As long-suffering nerve pain patients, neuropathy sufferers frankly couldn't give a damn what politicians' moral objections may be, they just want to know if marijuana is effective, why and how and then, if satisfied, be able to access it like any other proven treatment for their problem. This article is a must read for anyone considering taking medical marijuana in whatever form, for their neuropathy pain. If you have confidence in the treatment, progress almost always moves along more smoothly.
Recommended read.

The Progress and Pitfalls of Medical Marijuana  
By Katharine Quarmby | August 18, 2015 

“Cannabis is like a medicine cabinet,” says Roger Pertwee, who was instrumental in some of the early cannabis trials for multiple sclerosis. “It has a lot of compounds in it that are novel and unique to cannabis. We have discovered 104 so far, but there are others. There are many potential uses that we have to investigate.”

Pertwee is Professor of Neuropharmacology at the University of Aberdeen and also GW’s Director of Pharmacology (some of his research at the university is funded by the company). His work, alongside that of other researchers including Raphael Mechoulam and Vincenzo Di Marzo, is instrumental in our understanding of the endocannabinoid system, a network of lipids and receptors involved in a wide array of bodily processes, including appetite, memory, pain and mood.

We have two types of cannabinoid receptor: CB1, which is mostly found in the brain and spinal cord, and CB2, which is found mainly on cells in the immune system. These receptors are activated by cannabinoids made by the body (endocannabinoids) as well as synthetic cannabinoids and those present in plants.

Where should medical research focus its efforts exploring medical cannabis? Many prominent researchers, including Pertwee, believe that the individual components of cannabis are more effective than using the whole plant. Focusing on components would also obviate the need for a patient to smoke.

Areas of interest to researchers across the world include the possible therapeutic use of THC (the main psychoactive component of cannabis), CBD and other cannabinoids to treat autoimmune diseases, diabetes, cancer, inflammation, seizures and even psychiatric disorders, such as schizophrenia.

Cannabis for Cancer

At the medical school at St George’s, University of London, Dr Wai Liu and his team have shown that cannabinoids target the signalling pathways that are mutated in cancer cells, which, effectively, tell cells to keep growing. THC and CBD can turn these signals off, which may reverse the process of cancer in the cells. The compounds also enhance the action of radiotherapy.

But Liu, too, is skeptical of a whole-plant approach. “We have an amazing chance to use a drug derived from the cannabis plant which seems to be anti-cancerous. Let’s research it, and combine it with other cancer drugs. Let’s not waste time.

“If you truly believe that anti-cancer is the argument, don’t talk about cannabis any more, in the same way that we don’t talk about white willow any more because we have aspirin… We don’t need to be hijacked by other motives, like whether or not to legalize cannabis.”

The apparently encouraging results of this kind of work have led some patients to buy cannabis oil online, which is illegal in the UK. Liu is concerned that patients could be self-medicating with oil that could be contaminated. Another problem, he says, is that other chemicals within cannabis (minor cannabinoids) could actually counteract the beneficial effects of THC and CBD. He is now asking the many medical cannabis users who email him if he can collect their data, as a potential precursor to a full clinical trial. “We need to understand the drugs being sold on the internet,” he says.

These minor cannabinoids could be helpful too. Pertwee explains: “We were looking at the history of tincture of cannabis in the past. We found it contains tetrahydrocannabivarin (THCV)”. The researchers have since found that THCV blocks the CB1 receptor but partially activates the CB2 receptor. “This might be good for treating stroke and it might be good for drug dependence,” he says. Other potential uses are being investigated, including for Parkinson’s and schizophrenia. 

Evidence for Medical Marijuana

But it’s still early days. While some cannabis enthusiasts see it as a panacea – especially appealing when so many conditions aren’t well treated by other drugs – as yet, evidence across the board just isn’t there.

In summer 2015, a review of the efficacy of medical cannabis for a number of conditions was published. Examining 28 databases, the authors found moderate evidence that medical cannabis may help with spasticity in multiple sclerosis and with neuropathic and chronic pain. But evidence for other conditions was weaker.

One major charity, Cancer Research UK, has faced a particularly prominent backlash after voicing caution about cannabis. Its Science Communications Manager, Dr Kat Arney, showed me her bulging folder of research papers about cannabis, embellished with a sticker of Bob Marley. “Cannabinoids are really interesting molecules with potential for human health,” she says. “I read the literature regularly. Nothing tells me that cannabis is a cure for cancer.”

This cautious stance has led to the charity getting flamed on social media. Arney wants case studies to be gathered, saying that the way cannabis in its whole-plant form is discussed by the online community, uncritically, as a cure-all is unhelpful. “At the moment it sounds like – for want of a better word – snake oil, and that’s how it is marketed.”
Legalization Patchwork

Canada, Uruguay, Israel and Jamaica are among the countries that have ruled cannabis legal for medical use. Alongside these sit 23 American states and the District of Columbia, five of which, at the time of writing, have gone as far as legalizing recreational use too.

But what do we mean by medical use? Steve Rolles, from the international think-tank Transform, which campaigns for the legal regulation of drugs globally, sets out some of the options: “Do we want a standardized herbal product like Bedrocan [from specially grown plants], or a tincture like Sativex, or a single-content pharmaceutical product… or a combination of products?

“Would we allow people to ‘grow their own’, as some jurisdictions do, or be provided by ‘compassion clubs’? Who would regulate this activity?”

The stated purpose of most of the American state laws is based on the Californian law: “to ensure that seriously ill Californians have the right to obtain and use marijuana for medical purposes where that medical use is deemed appropriate.” But there is conflict with federal law, under which cannabis is still illegal, and models vary widely across state lines. Alice O’Leary-Randall, one of the earliest American pioneers in the medical cannabis field, says this variation has scattered the movement and dubs it “medical cannabis by zip code.”

Most of these states require the patient to have some form of license to acquire medical cannabis but not all require state residency. Although almost all states have a list of conditions that qualify for medical cannabis, these differ, with some states permitting it for chronic conditions and others only for specified illnesses such as cancer.

Data collected in some states suggests that many medical users receive cannabis for chronic or severe pain, a catch-all, rather than for the conditions on which the first activists campaigned: glaucoma, AIDS, cancer and multiple sclerosis. Certified users in Arizona, for example, are mostly young and male and use the drug for pain relief.
From Medical to Recreational

This, opponents argue, is evidence that medical cannabis has become a first step on the road to recreational legalization, rather than an end in itself. Kevin Sabet, who advised the Obama administration on drug policy, now works as a consultant with Smart Approaches to Marijuana, an organization that opposes legalization. “In the US we are seeing that medical cannabis is being misused to legitimize recreational use,” he says.

“We know that the political movement on medical marijuana is tied to legalization… they have rebranded cannabis, from being about 30-year-old stoners to medical use.” Successfully, too: a 2013 Fox News poll found that 85 percent of Americans – and 80 percent of self-identified Republicans – approve of the medical use of cannabis if prescribed by a medical doctor. But you don’t even need a doctor in some states, as homeopaths and naturopaths can issue licenses.

The amount of cannabis allowed varies. Some states allow patients to grow their own. Others have restrictive medical cannabis agreements, allowing only high-CBD strains (for particular conditions such as epilepsy) – so restrictive, in fact, that patients argue that they are unworkable. The Drug Enforcement Administration has also raided cannabis dispensaries countrywide, saying that they are not just serving medical users.

“There are serious impediments to medical cannabis use within our healthcare system,” O’Leary-Randall says. “There is no consistent education of our healthcare professionals around using medical cannabis, or the endocannabinoid system.” She sits on the board of the American Cannabis Nurses’ Association, which was set up formally in 2012 to give nurses advice on how to assist patients and dispense safely, without violating federal law or their license.

Pharmacists, too, walk a tightrope. Nearly 20 years after the legalization of medical cannabis, the American Society of Health-System Pharmacists (an official body for the profession) encourages research into, but not distribution of, medical cannabis, so qualified pharmacists have historically been unwilling to get involved. Recent discussions by the body, however, suggest a softening of attitude towards medical cannabis. A new body, the National Association of Cannabis Pharmacy, was launched last year.

O’Leary-Randall wants more qualified pharmacists to be involved in dispensing cannabis, though she acknowledges the difficulties: “Cannabis is so unique… It’s rather daunting for elderly people to go into a dispensary and look at names like Purple Haze and Skunk Weed and pick out what is their medicine. I would love to see pharmacists more active in this so we can standardize this and get people more comfortable.”

This story first appeared on Mosaic. It has been excerpted here.

Wednesday, 19 August 2015

Acupuncture And Amitriptilyine Trial For HIV Neuropathy

Today's long (apologies) post from (see link below) sort of follows on from yesterday's post about amitriptyline and gives a historical perspective to the arguments that amitriptyline has never been proved to help relieve neuropathy symptoms. In this case, the trial subjects were neuropathy sufferers living with HIV. It's quite a read but an interesting one and gives us an insight into how such studies are carried out, what their objectives are and what sort of conclusions they reach. It's not often that we, as patients, get the chance to see how the system works and be able to examine independent studies for ourselves but this one does. Also interestingly, it looks at a study of how a complimentary treatment (acupuncture) and a standard medical treatment can be evaluated together. It comes from 1998 but as yesterday's post shows, some things never change and that's not always to our benefit. Why, for instance, are we still being prescribed amitriptyline for neuropathic pain, when it's consistently proved to be no better than a placebo?
n.b. You may have to refer to the original link to be able to look at the tables in detail.

Acupuncture and Amitriptyline for Pain Due to HIV-Related Peripheral Neuropathy A Randomized Controlled Trial 
Judith C. Shlay, MD; Kathryn Chaloner, PhD; Mitchell B. Max, MD; Bob Flaws, Dipl, Ac; Patricia Reichelderfer, PhD; Deborah Wentworth, MPH; Shauna Hillman, MS; Barbara Brizz, BSN, MHSEd; David L. Cohn, MD; for the Terry Beirn Community Programs for Clinical Research on AIDS

November 11, 1998, Vol 280, No. 18 

JAMA. 1998;280(18):1590-1595. doi:10.1001/jama.280.18.1590.


Context.— Peripheral neuropathy is common in persons infected with the human immunodeficiency virus (HIV) but few data on symptomatic treatment are available.

Objective.— To evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients.

Design.— Randomized, placebo-controlled, multicenter clinical trial. Each site enrolled patients into 1 of the following 3 options: (1) a modified double-blind 2 × 2 factorial design of SAR, amitriptyline, or the combination compared with placebo, (2) a modified double-blind design of an SAR vs control points, or (3) a double-blind design of amitriptyline vs placebo.

Setting.— Terry Beirn Community Programs for Clinical Research on AIDS (HIV primary care providers) in 10 US cities.

Patients.— Patients with HIV-associated, symptomatic, lower-extremity peripheral neuropathy. Of 250 patients enrolled, 239 were in the acupuncture comparison (125 in the factorial option and 114 in the SAR option vs control points option), and 136 patients were in the amitriptyline comparison (125 in the factorial option and 11 in amitriptyline option vs placebo option).

Interventions.— Standarized acupuncture regimen vs control points, amitriptyline (75 mg/d) vs placebo, or both for 14 weeks.

Main Outcome Measure.— Changes in mean pain scores at 6 and 14 weeks, using a pain scale ranging from 0.0 (no pain) to 1.75 (extremely intense), recorded daily.

Results.— Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values. For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the 2 groups. At 6 weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the "active" treatment) was 0.01 (95% confidence interval [CI], −0.11 to 0.12; P =.88) and for patients in the amitriptyline group vs those in the placebo group was −0.07 (95% CI, −0.22 to 0.08; P=.38). At 14 weeks, the difference for those in the SAR group compared with those in the control points group was −0.08 (95% CI, −0.21 to 0.06; P=.26) and for amitriptyline compared with placebo was 0.00 (95% CI, −0.18 to 0.19; P=.99).

Conclusions.— In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.

PERIPHERAL NEUROPATHIES are diagnosed in 30% to 35% of patients with human immunodeficiency virus (HIV) and cause pain and dysesthesias.1,2 Symptomatic treatment includes antidepressants, nonnarcotic and narcotic analgesics, anticonvulsants, and acupuncture.2,3 The use of these treatments is based on anecdotal4 information and trials in other disease conditions.5

We chose to examine the efficacy of 2 commonly used treatments, amitriptyline hydrochloride and acupuncture, for HIV-related peripheral neuropathy. Amitriptyline is frequently prescribed for neuropathic pain and has been shown to be an effective treatment for diabetic, hereditary, toxic, and idiopathic neuropathies.6,7

Although several trials that reported examining acupuncture for chronic painful conditions claim efficacy,8,9 these studies have methodological limitations, including small sample sizes and inadequate controls for the nonspecific effects of acupuncture.9- 11 Meta-analyses of studies of acupuncture for chronic pain show a response rate of approximately 70% for acupuncture, 50% for "sham" acupuncture (needling points not considered effective), and 30% for control treatments, such as sham transcutaneous electrical nerve stimulation.9,10,12,13

To evaluate the effect of both a nonstandard and standard medical therapy for peripheral neuropathy, we performed a multicenter, modified double-blind, randomized, placebo-controlled study of the separate and combined efficacy of a standardized acupuncture regimen (SAR) and amitriptyline for the relief of pain caused by HIV-related peripheral neuropathy.


Study Design

We used a 2×2 factorial design to determine whether SAR, amitriptyline, or the combination was more effective than placebo. The SAR consisted of acupuncture points chosen by the study acupuncturists and several consultants to be effective for peripheral neuropathic pain. This regimen was compared with control points that were not "true" points defined by any standard acupuncture text14 (Figure 1). We compared the efficacy of amitriptyline with placebo capsules of identical appearance. Enrollment in the factorial design began in May 1993, but patients at some sites were reluctant to be randomized to receive amitriptyline and some clinicians were unwilling to provide amitriptyline to their patients because it was a commonly abused drug in their communities. The study design was modified in March 1995 so that sites could choose only 1 of 3 options. Each site could (1) continue to enroll into the factorial design (factorial option), (2) enroll into a single-factor design of SAR vs control points (acupuncture option), or (3) enroll into a single-factor design of amitriptyline vs placebo (amitriptyline option) (Figure 2).

Figure 1.—Standardized acupuncture regimen and control points.

View Large | Save Figure | Download Slide (.ppt)

Figure 2.—The standardized acupuncture regimen (SAR) vs control points (CPs) compares n1 + n3 + n5 with n2 + n4 + n6. The amitriptyline vs placebo compares n1 + n2 + n7 + with n3 + n4 + n8.

View Large | Save Figure | Download Slide (.ppt)

Randomization schedules were prepared using random blocks stratified by unit. Patients were randomized to treatment by the study units by telephoning the Statistical Center at the University of Minnesota, Minneapolis. The unit pharmacists were the only people unblinded to the placebo vs amitriptyline assignment, and the acupuncturists were the only people unblinded to the SAR vs control points assignments. The pain diaries and the assessments of pain relief were collected by study staff who were blinded to the treatment assignments.

Study Population

Patients were recruited from 11 units of the Terry Beirn Community Programs for Clinical Research on AIDS, an organization sponsored by the National Institutes of Health, which conducts clinical trials in primary care settings. The study was approved by each institutional review board. All participants gave written informed consent. To be eligible, participants had to be aged 13 years or older; have documented HIV infection; have symptoms of HIV-related lower extremity peripheral neuropathy, diagnosed by a physician based on history and clinical examination; and have completed a baseline pain diary prior to randomization. Antiretroviral therapy was allowed and dosages of analgesic medication or herbal therapies used at randomization were maintained or reduced. The initiation of new treatments during the study was discouraged but allowed when necessary. Patients were excluded if they were being treated for an acute opportunistic infection or malignancy except nonsystemic Kaposi sarcoma, were pregnant, or had taken a tricyclic antidepressant or monoamine oxidase inhibitor 2 weeks before randomization.

Treatment Regimens

For the acupuncture comparison, patients were randomly assigned to receive SAR or control points twice weekly during a 6-week induction phase, followed by weekly treatment during an 8-week maintenance phase. This SAR was based on a Chinese theory that peripheral neuropathy caused by diabetes and HIV-related peripheral neuropathy have similar mechanisms. The SAR included spleen points 9, 7, and 6, with the additional supplemental points of Ba Feng (M-LE-8) for complaints of pain or numbness in the toes, Ran Gu (kidney 2) for complaints of pain or numbness in the soles, and Tai Ki (kidney 3) for complaints of pain or numbness in the heel (Figure 1).14 The control points were located on the back of the leg (Figure 1). For the SAR and control points, acupuncture needles were inserted to a specified depth. Each location was manipulated both superiorly and inferiorly. Then the needles were reinserted into the specified point. After 10 to 15 minutes, the needles were remanipulated and replaced into the original location for another 5 to 10 minutes. The depth of insertion was between 1.28 to 2.54 cm (0.5 to 1.0 in) for spleen point 9, 2.54 to 3.81 cm (1.0 to 1.5 in) for spleen point 7, and 1.5 to 3.05 cm (0.6 to 1.2 in) for spleen point 6. For the control points, insertion was less than 1.28 cm (0.5 in). Study acupuncturists received standardized training in the technique. In addition, a videotape of the acupuncture and the control treatment was provided to each of the acupuncturists in the study. To maintain blinding and to determine the need for supplemental points, the acupuncturists asked all patients a series of standard questions, irrespective of treatment arm. For those in the SAR group, spleen points 9, 7, and 6 were always used. Supplemental acupuncture points were used only if the patient answered "yes" to the corresponding question. The control points consisted of only 3 specified points.

For the amitriptyline comparison, the patients were randomized to receive a 14-week course of either amitriptyline or placebo capsules by mouth once a day. They were instructed to take them between 1 to 2 hours before bedtime. An initial daily dose of 25 mg of amitriptyline hydrochloride was increased every 2 to 3 days until a maximum dosage of 75 mg/d was reached.15,16 The placebo capsules were identical in appearance and taste to the active capsules. Patients were followed up for the 14-week study period and for adverse event monitoring for an additonal 8 weeks after the study treatment had discontinued.

Results were monitored by the HIV Therapeutic Trials Data Safety and Monitoring Board of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Data monitoring used the Lan–De Mets method17 as a guideline for early stopping to account for increased type I error probability by examining the data before the designed study end.


Patients rated their pain in a diary once daily, choosing from the Gracely scale of 13 words that describe the intensity.18 The scale ranges from no pain (0.0), weak (0.45), mild (0.74), moderate (1.09), strong (1.36), to extremely intense (1.75). The words had been assigned magnitudes on the basis of ratio-scaling procedures that demonstrated internal consistency, reliability, and objectivity.18 The scale has distinguished active from control interventions in experimental and clinical pain studies.6,18,19 At the end of both the induction and maintenance phases, patients reported their global pain relief (complete, a lot, moderate, slight, none, or worse) after they were asked the following question: "Since the beginning of the study, how would you rate the relief of pain and/or discomfort in your legs and feet?" A study physician, trained in neurologic examination, tested the patient at randomization and at 14 weeks. A neurologic summary score was computed as an average of 3 separate scores for muscle strength, sensory ability, and reflex. Each physician who performed the neurologic assessment reviewed a videotape that detailed how the examination was to be completed. The patients also completed a self-administered, 39-item, quality-of-life assessment tool.20 The complete tool, consisting of 11 different dimensions, was administered at baseline and 14 weeks, and the dimension corresponding to physical functioning was also administered at 6 weeks. To assess the effectiveness of the blinding, all patients were asked to guess their treatment assignments at 14 weeks. Patients were monitored for grade 4 adverse events and death. Adverse experiences occurring within 8 weeks of study treatment were graded on a 5-point severity scale (grade 5 corresponding to death) according to a standardized toxicity scale. Any grade 4 or 5 event was reportable irrespective of presumed relationship to study treatment.

Statistical Analysis

Comparison of treatment groups for the primary end point of change in pain, as measured by the pain diary, used a linear model with baseline characteristics, clinical unit, and option (factorial or single factor) as covariates. If the average weekly pain score for the sixth week of treatment was present, it was used. If it was missing, the closest weekly average within the 6-week visit window of 4 to 10 weeks was used. Similarly, this was done for the 14-week end point and the visit window of 11 to 16 weeks. A linear model repeated measures analysis of the weekly pain averages was also performed, with the same explanatory variables.21 Estimates of the difference between SAR and control points were calculated for each of the 14 weeks. The global pain relief rating was analyzed using a log-linear model, with likelihood ratio tests for differences among treatment groups, which were adjusted for option.22

We verified that results from the 3 treatments could be pooled by checking that the interaction term between acupuncture and amitriptyline in the factorial option and the option by treatment interaction were nonsignificant.

Secondary outcomes were the permanent discontinuation of study treatments, changes in quality of life, and changes in neurologic summary scores, which were analyzed similarly to the primary end point. All analyses were on an intent-to-treat basis. The evaluation of the blinding compared the patients' guesses of the therapy received with the treatment group. Using a log-linear model, we adjusted for option and for whether the patient reported moderate or more pain relief with the 14-week global pain relief rating.

For the original 2×2 factorial design, a sample size of 260 patients was calculated to provide a 90% power of detecting a mean difference between treatments of 0.20 (half the difference between "moderate" and "mild" pain) on the Gracely pain intensity scale using a type I error of .05 (2-sided). After the study design was modified, sample size requirements were estimated at 260 per group. In February 1997, the monitoring board recommended closing the study because it concluded that the results were definitive for both acupuncture and amitriptyline comparisons.


Study Population

From May 1993 to February 1997, 250 patients were enrolled. Of those, 239 were in the acupuncture comparison (125 in the factorial option and 114 randomized to SAR or control points), and 136 were in the amitriptyline comparison (125 from the factorial option and 11 randomized to either active or placebo amitriptyline) (Figure 2). Baseline characteristics (Table 1) were similar in the active and control groups for both comparisons.

Table 1.—Baseline Characteristics of Study Participants*

View Large | Save Table | Download Slide (.ppt)

Effects of Treatment

SAR vs Control Points.— The change in pain was not significantly different between the 2 groups at either 6 or 14 weeks (Table 2). Both groups showed improvement in pain from an average intensity of "moderate" to "mild" (Figure 3). The estimated difference of the SAR group compared with the control points group was 0.01 at 6 weeks (95% confidence interval [CI], −0.11 to 0.12; P =.88) and −0.08 at 14 weeks (95% CI, −0.21 to 0.06; P=.26). At 6 weeks, the SAR group had less pain relief than patients in the control points group by 0.01 U and at 14 weeks, the SAR group had 0.08 U more relief than patients in the control points group. Repeated measures analyses of weekly pain averages during the entire 14-week period gave weekly effects, which were small and nonsignificant (P values ranging from .10 to .94).

Table 2.—Mean Changes in Weekly Pain Diary Scores, Neurologic Score, and Quality of Life at 6 and 14 Weeks*

View Large | Save Table | Download Slide (.ppt)

Figure 3.—Average pain intensity scores for single factor options by study week. The mean weekly values of the descriptors of pain intensity are plotted. There was no statistically significant difference between the effects of the standardized acupuncture regimen (SAR) vs control points or between amitriptyline vs placebo. Pain intensity is described and rated as no pain (0.0), faint (0.04), very weak (0.36), weak (0.45), very mild (0.59), mild (0.74), moderate (1.09), barely strong (1.10), slightly intense (1.35), strong (1.36), intense (1.59), very intense (1.64), and extremely intense (1.75).18

View Large | Save Figure | Download Slide (.ppt)

There were no significant differences in the quality of life, neurologic summary score (Table 2), number of grade 4 adverse events, deaths, or discontinuations. By 14 weeks, 20% of patients randomized to the SAR group and 25% of those randomized to control points group had discontinued treatment. Three patients assigned to the SAR option and 10 assigned to the control points experienced a grade 4 adverse event (P=.06).

The difference in the global pain relief rating between the 2 groups was not significant at 6 weeks (P=.65). However, at 14 weeks, there was a nominally significant difference (P=.03) with a slightly higher proportion of patients in the SAR group reporting moderate or more pain relief than those in the control points group (Table 3). However, after adjustment for multiple comparisons, the result is not significant.

Table 3.—Global Pain Relief Rating at 6 and 14 Weeks*

View Large | Save Table | Download Slide (.ppt)

Amitriptyline vs Placebo.— The change in pain score at 6 and 14 weeks was not significantly different between the active and placebo groups (Table 2). As with the SAR vs control points comparison, both groups showed improvement over time (Figure 3). The estimated difference of amitriptyline compared with placebo was −0.07 at 6 weeks (95% CI, −0.22 to 0.08; P=.38) and 0.00 at 14 weeks (95% CI, −0.18 to 0.19; P =.99). That is, at 6 weeks, patients taking amitriptyline had more pain relief by 0.07 U than those taking placebo and there was no difference at 14 weeks. Repeated measures analyses of weekly pain averages indicated that the largest beneficial effect was at week 3 (P=.05), but after adjusting for multiple comparisons, the result was not statistically significant.

There were no statistically significant differences in quality of life, neurologic summary scores (Table 2), number of grade 4 adverse events, or deaths. Six patients assigned to the amitriptyline and 2 assigned to placebo options experienced grade 4 adverse events (P=.20). By 14 weeks, 35% of patients randomized to either the amitriptyline or placebo groups had discontinued drug treatment. The difference in the global pain relief rating between the 2 groups was not significant at 6 weeks (P=.68) or 14 weeks (P=.81) (Table 3).

Factorial Option.— The test for interaction in change of pain between the 2 factors was not significant at either 6 or 14 weeks (P=.17 and P =.31, respectively). There was no significant difference in the change in pain among the 4 groups at either 6 or 14 weeks (P=.37 and P =.64, respectively). All study groups in the factorial option showed improvement in pain.

Completeness of Data

Figure 2 shows the number of patients providing pain diary data and global pain relief ratings at 6 and 14 weeks. To examine the sensitivity of the conclusions to missing data, the analyses were repeated using 2 common methods to impute missing data. The first assumes that the patients' missing data indicated no change in their pain from baseline; the second uses the last value of the weekly pain reported to calculate the end point. Under both methods to impute the missing pain diary data, the results of the study did not reach statistical significance for either comparison at either 6 or 14 weeks.

Assessment of Treatment Blinding


For the acupuncture comparison, although the patients' guesses and the treatment assignments were not independent (P=.007, data not shown), there was a strong association between the guess and the global pain relief rating. Those reporting moderate or more relief at 14 weeks tended to guess that they received the SAR. After adjusting for option and the reported relief being moderate or more, the patients' guesses and the treatment assignments were not independent (P=.02), but the association was small. This differed in the amitriptyline comparison, in which a large proportion of patients correctly guessed the study treatment, irrespective of their level of pain relief (P<.001) (Table 4).

Table 4.—Effectiveness of Participants' Blinding to Treatment Assignment*

View Large | Save Table | Download Slide (.ppt)


The main findings of this study show that treatment with this SAR had little or no effect on HIV-related peripheral neuropathy compared with the control points. Similarly, amitriptyline, as commonly used, was not significantly more effective than placebo (Table 2 and Figure 3). All treatment groups improved during the study period by the amount hypothesized in the design, suggesting that the modest decline in pain scores in all groups was either attributable to a placebo effect or patients entered the study at times of symptomatic flares and improved spontaneously thereafter.

For the acupuncture comparison, the results were strengthened by 2 methodological features of the trial. First, the sample size of approximately 120 patients per treatment group is many times larger than those in previously published trials of acupuncture,9 and the CIs were narrow, making it unlikely that a large positive treatment effect was missed by chance. Second, the control points appeared reasonably effective in preserving the blinding (Table 4). Many of the study clinicians and, presumably, the study participants were favorably disposed toward acupuncture. If patients were able to guess their treatment better than randomly, the resulting placebo effects would be expected to bias the result in favor of this SAR,10,12,24 thus making our finding of a similar effect even more convincing.

We cannot completely rule out the possibility that the SAR had a modest and delayed analgesic effect, in view of the nominally significant result of SAR compared with control points on the global pain relief rating at 14 weeks, although this was not seen at 6 weeks. This is unlikely, however, in view of the finding of no significant difference in the pain diary scores. Our study was designed with a sample size that provided sufficient power to detect even a small difference between the SAR and control points. The CIs at both 6 and 14 weeks rule out any clinically meaningful beneficial effects of SAR based on the primary end point of the pain diary scores.

One possible explanation for the lack of efficacy of the SAR is that we chose the wrong "active points." Consensus on the SAR was reached by 8 acupuncturists before protocol implementation. Another explanation is that the use of nonclassical points as a control provided a real effect and was not an inert control. There is evidence from animal and human studies that acupuncture at either classical or nonclassical locations may have analgesic effects9,25,26 by mechanisms such as the release of endogenous opioids27 or activation of other brain and spinal cord pathways that reduce pain.28

There is controversy over what constitutes an acceptable control group for acupuncture studies.8,29 It is possible that the novelty of an experience like acupuncture may generate a placebo analgesic effect quite apart from specific effects produced by needling specific points.30 Unless the study includes a "sham" acupuncture group as a control, such nonspecific effects may bias toward a result in favor of the active intervention.

The SAR chosen for this study differs from the practice of most acupuncturists, who treat patients with individualized regimens.31 We chose to study standardized points to test the hypothesis that these specific points promote analgesia for chronic foot and leg pain13 and because such a study is easier to blind and replicate. If the acupuncturists had used individualized treatment, the results would not be generalizable to other acupuncturists, and the treatment, if efficacious, could not be used by other practitioners. Our approach enabled us to derive a conclusion about these acupuncture points but not about individualized treatments.

Amitriptyline is used in the treatment of HIV-related peripheral neuropathy32 but was not effective in this study. The lack of efficacy at 14 weeks was confirmed by the analysis of the secondary end points. Although the 6-week CI did not completely rule out the beneficial effect of 0.20 that the study was designed to detect, there was no supporting evidence of beneficial effect from any of the secondary end points. In addition, another study in HIV-related peripheral neuropathy agrees with our findings.33 The indication that the blinding was not maintained also confirms the lack of efficacy because unblinding tends to bias toward a hypothesized active intervention.24,34

It is possible that a higher dose of amitriptyline would have resulted in a larger treatment effect. We chose this dose based on common clinical practice and on the only 2 published prospective randomized dose-response studies of tricyclic antidepressants used for chronic pain.15,16

No previously controlled trials of amitriptyline in neuropathic pain have followed up patients for longer than 8 weeks.33,35 Clinical trials of amitriptyline for neuropathies of diabetic and nondiabetic etiologies have shown larger, short-term, clinically meaningful effects.6,7,19 Mechanisms for this include facilitation of the analgesic action of norepinephrine and serotonin released by endogenous analgesic systems16,19 and the blockade of sodium channels in peripheral sprouts from damaged nerves.36 Presumably, the neuropathological features of the HIV-associated distal axonal neuropathy generate painful discharges resistant to the analgesic actions of tricyclic antidepressants.37,38

In conclusion, this is the largest reported randomized, placebo-controlled, clinical trial of symptomatic treatment for HIV-related peripheral neuropathy. Overall, our results indicate that neither this SAR given over 14 weeks nor amitriptyline hydrochloride, 75 mg/d, was effective in relieving pain and neither therapy can be recommended for the treatment of HIV-related peripheral neuropathy. Additional clinical trials are needed because there are no effective treatments for this chronic debilitating condition.39


So YT, Holtzman DM, Abrams DI, Olney RK. Peripheral neuropathy associated with AIDS. Arch Neurol.1988;45:945-948.

Simpson DM, Tagliati M. Neurologic manifestations of HIV infection. Ann Intern Med.1994;121:769-785.

Armington K. Sticking it to peripheral neuropathy. AIDS Care.1997;9:52-54.

Newshan G. HIV neuropathy treated with gabapentin. AIDS.1998;12:219-221.

Hegarty A, Portenoy RK. Drug therapy for neuropathic pain. Semin Neurol.1994;14:213-224.

Max MB, Culnane M, Schafer SC. et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology.1987;37:589-596.

Vrethem M, Boivie J, Arnquist H. et al. A comparison of amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. Clin J Pain.1997;13:313-323.

Birch S, Hammerschlag R, Berman BM. Acupuncture in the treatment of pain. J Altern Complement Med.1996;2:101-124.

Richardson PH, Vincent CA. Acupuncture for the treatment of pain. Pain.1986;24:15-40.

Chapman CR, Gunn CC. Acupuncture. In: Bonica JJ, ed. The Management of Pain . 2nd ed. Malvern, Pa: Lea & Febiger; 1990:1805-1821.

Patel M, Gutzwiller F, Paccaud F, Marazzi A. A meta-analysis of acupuncture for chronic pain. Int J Epidemiol.1989;18:900-906.

Deyo RA. Non-operative treatment. In: Frymoyer JW, ed. The Adult Spine: Principles and Practice . New York, NY: Raven Press; 1991:1777-1793.

Lewith GT, Machin D. On the evaluation of the clinical effects of acupuncture. Pain.1983;16:111-127.

O'Connor J, Bensky D. Acupuncture: A Comprehensive Text . Chicago, Ill: Eastland Press; 1981.

McQuay HJ, Carroll D, Glynn CJ. Dose-response for analgesic effect of amitriptyline in chronic pain. Anaesthesia.1993;48:281-285.

Sindrup SH, Gram LH, Skjold T. et al. Concentration-response relationship in imipramine treatment of diabetic neuropathy symptoms. Clin Pharmacol Ther.1990;47:509-515.

Lan KKG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika.1983;70:659-663.

Gracely RH, McGrath P, Dubner R. Ratio scales of sensory and affective verbal pain descriptors. Pain.1978;5:5-18.

Max MB, Lynch SA, Muir J. et al. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med.1992;326:1250-1256.

Tarlov AR, Ware Jr JE, Greenfield S. et al. The Medical Outcomes Study: an application of methods for monitoring the results of medical care. JAMA.1989;262:925-930.

Littell RC, Milliken GA, Stroup WW, Wolfinger RD. SAS System for Mixed Models . Cary, NC: SAS Institute Inc; 1996.

Agresti A. An Introduction to Categorial Data Analysis . New York, NY: John Wiley & Sons Inc; 1996.

O'Brien PC. Procedures for comparing samples with multiple endpoints. Biometrics.1984;40:1079-1087.

Turner JA, Deyo RA, Loesor JD. et al. The importance of placebo effects in pain treatment and research. JAMA.1994;271:1609-1614.

Lee PK, Andersen TW, Modell JH, Saga SA. Treatment of chronic pain with acupuncture. JAMA.1975;232:1133-1135.

Gaw AC, Chang LW, Shaw LC. Efficacy of acupuncture on osteoarthritic pain. N Engl J Med.1975;293:375-378.

Han JS, Chen XH, Sun SL. et al. Effect of low- and high-frequency TENS on Met-enkephalin-Arg-Phe and dynorphin A immunoreactivity in human lumbar CSF. Pain.1991;47:295-298.

LeBars D, Dickerson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC): effects on dorsal horn convergent neurones in the rat. Pain.1979;6:283-304.

National Institutes of Health Consensus Conference. Acupuncture. JAMA.1998;280:1518-1524.

Norton GR, Goszer L, Strub H, Man SC. The effects of belief on acupuncture analgesia. Can J Behav Sci.1984;16:22-29.

Vincent CA, Richardson PH. The evaluation of therapeutic acupuncture. Pain.1986;24:1-13.

Fauci AS, Lane HC. Human immunodeficiency virus (HIV) disease. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine . 14th ed. New York, NY: McGraw-Hill; 1998:1790-1855.

Kieburtz Z, Yiannoutsos CP, Simpson D.and ACTG 242 Study Team. A double-blind, randomized clinical trial of amitriptyline and mexiletine for painful neuropathy in human immunodeficiency virus infection. Ann Neurol.1997;42:429.

Thomson R. Side effects and placebo amplification. Br J Psychiatry.1982;140:64-68.

Max MB. Antidepressants as analgesics. In: Fields HL, Libefkind JC, eds. Pharmacological Approaches to the Treatment of Chronic Pain . Vol 1. Seattle, Wash: International Association for the Study of Pain Press; 1994:229-246.

Jett MF, McGuirk J, Waligora D, Hunter JC. The effects of mexiletine, desipramine and fluoxetine in rat models involving central sensitization. Pain.1997;69:161-169.

Dalakas MC, Pezeshkpour GH. Neuromuscular diseases associated with human immunodeficiency virus infection. Ann Neurol.1988;23 Suppl:S38-S48.

Tyor WR, Wesselingh SL, Griffin JW. et al. Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy. J Acquir Immune Defic Syndr Hum Retrovirol.1995;9:379-388.

Simpson DM, Dorfman D, Olney RK. et al. Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. Neurology.1996;47:1254-1259.