Braille Monitor                                                    June 2009

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Diabetic Peripheral Neuropathy

From the Editor: This article first appeared in the Voice of the Diabetic, Volume 18, Number 4, Fall 2003. It has been updated to reflect developments in treatment of diabetic neuropathy and changed Website links. Diabetic neuropathy is or should be of significant interest to all diabetics. Aside from causing pain and often being a major contributor to amputation, it prevents some diabetics from learning or reading Braille. Understanding this complication should motivate many diabetics to work just that much harder to keep their disease under good control. Here is some useful information:

What is Neuropathy?

Neuropathy is a general term for physical damage to or impairment of the human nervous system. It has many causes and many symptoms. Because a long period with elevated blood glucose can damage nerve fibers, diabetes is one of several major causes of neuropathy (others being AIDS and multiple sclerosis.) The Centers for Disease Control suggests up to 70 percent of diabetics may have measurable neuropathy, though a number of other diseases (and some medications) can also cause this condition. The presence of unexplained neuropathy is a warning flag that you need to find out where these symptoms are coming from.

"Diabetic neuropathy occurs in both type 1 and type 2 diabetes," says InteliHealth, an Internet magazine now affiliated with Harvard Medical School, "and it is most common in those whose blood glucose levels have been poorly controlled. Although diabetic neuropathy can occur in patients who have had diabetes for a short time, it is most likely to affect those who have been diabetic for more than a decade, especially those over age forty. Diabetics who smoke are especially at risk."

The human nervous system is enormously complex. The peripheral nerves carry information to and from the brain, connecting it with the rest of the body. These nerves can be motor, sensory, or autonomic. Motor nerves carry messages from the brain for the contraction of various muscles. Sensory nerves relay sensations of touch, temperature, position, and pain from the body's periphery to the brain. Autonomic nerves carry the brain's commands to organs such as the heart, stomach, lungs, and liver; autonomic neuropathy, a potentially severe condition, though thankfully rare, will receive its own separate coverage later.

The longer the nerve fibers, the more likely they are to show damage from long-term high blood glucose. Such damage generally manifests at the nerve terminus, the end furthest away from the central nervous system (brain and spine). For peripheral neuropathy, symptoms commonly appear at the nerve terminals of feet, lower legs, and hands. Doctors call this common form distal sensory polyneuropathy.

Symptoms of early neuropathy can include diminished tactile sensation, numbness, loss of reflex reaction, and various types and degrees of pain, from pins and needles to extreme burning sensations. As neuropathy progresses, the symptoms frequently change. Diabetics experiencing neuropathy sometimes have other ramifications as well, and these have their own symptoms. Sometimes symptoms overlap, and diagnosis can be confusing. Diabetic nephropathy―kidney failure―can exacerbate neuropathy, due to the uremic toxicity of the condition. Other pain can be a symptom of undiagnosed orthopedic problems, unrelated medical conditions, drugs and medications, or exposure to toxic chemicals. If you are experiencing pain or abnormal sensations in hands, feet, or legs, or experiencing unusual difficulties with bodily processes, check with your doctor.

The simplest way for your doctor to check for the diminished sensation that can be an early sign of neuropathy in your feet is with a monofilament, a thin, flexible filament of nylon or broomcorn. The doctor will press it gently against areas of your foot and lower leg and ask you if you can feel the touch. Where you cannot, early neuropathy may be present. The monofilament, the only tool this test requires, is extremely inexpensive, and the test is highly advisable.

More sophisticated tests can be carried out with a tuning fork or, where the doctor needs to inspect a nerve path more closely, by a test called an electromyelogram (EMG). The EMG, which tracks the movement of electrical impulses along the nerve path, can reveal whether impairment is due to diabetes, a compression injury such as back problems or carpal tunnel syndrome, or some other cause. As neuropathy progresses, sensory nerves frequently stop working, and numbness becomes the most frequent symptom, bringing with it the end of pain, but a whole new set of problems.

Prevention and Treatment

Since diabetic neuropathy follows extended periods of hyperglycemia, its best prevention is good blood glucose management, tight control, with test results, blood glucose numbers in the normal range. A healthy lifestyle, with plenty of exercise and careful attention to diet, helps too. Incidentally, the same tight-control regime can help those with already established neuropathy. Although it is not clear exactly how it happens (there are several theories), experience shows that getting your diabetes under control and keeping it there can, over a several-month period, alleviate at least some of neuropathy's symptoms. Doctors argue whether neuropathy damage is reversible--but it may be, and you owe it to yourself to try.

Individual symptoms are as varied as individuals, but the most common complaint in the early stages is pain, and pain control becomes the single biggest challenge in dealing with established neuropathy. Doctors have prescribed aspirin, acetaminophen, and various other nonsteroidal anti-inflammatory drugs; the anticonvulsants Dilantin and carbamazepine (Tegretol); and tricyclic antidepressants such as paroxetine (Paxil) and amytriptaline (Elavil); or a combination of vitamins B1, B6, and Glutamine, with varying results. The U.S. Food and Drug Administration (FDA) has approved Pfizer’s antiseizure medication pregabalin (Lyrica) and Eli Lilly’s antidepressant duloxetine (Cymbalta) for the treatment of diabetic peripheral neuropathic pain. Along with the drugs some physicians are prescribing capsaicin cream (Zostrix and its equivalents), a topical ointment originally formulated for arthritis pain. Some use the epilepsy drug gabapentin (Neurontin, a predecessor to pregabalin that now has a generic equivalent), while others relieve symptoms with local anesthetics or muscle relaxants. Still others are investigating acupuncture, although not enough is known about it to say for certain how it works in such cases.

New research using lidocaine (a topical analgesic sold in creams, such as Lanacane, for treatment of itching and skin pain) shows promise. A team from Rochester School of Medicine used transdermal patches containing lidocaine 5 percent, applied topically to areas of maximum neuropathy pain. In a three-week, open-label test, patients reported a mean 63.1 percent improvement in pain symptoms--and this without anesthetics or recourse to powerful systemic drugs that could interact with other patient medications. Further study is under way.

Another option is mechanical, using radiant energy. Anodyne Therapy LLC, from Tampa, Florida, offers anodyne neuropathy care. Their noninvasive, FDA-cleared device uses near-infrared light emitted directly into the affected area. The light penetrates deeply and causes capillary vasodilation, in much the same way topically applied nitroglycerine cream would--but with less risk. Company data suggest the treatment is not just effective against neuropathy pain, but that it also restores lost sensation as measured by monofilament test and by patient interview. Anodyne postulates that its product stimulates release of endogenous nitric oxide in much the same way as do morphine and oxycontin but without the risks of these drugs. Their data suggest a combination of tight glycemic control (ending further hyperglycemic attacks to tissues and nerves) and effective vasodilator treatment (as with their product) can produce an observable reversal of loss of sensitivity. The device appears to treat both neuropathy pain and numbness and has clear benefits toward healing the stubborn ulcerated wounds that often follow neuropathy of the feet. A cursory look at the science behind the assertions suggests it is solid and that this device is free from the cant, touchy-feely, and carny-barker hucksterism that have plagued this field. Time will tell; keep your fingers crossed. And note, neither the Anodyne nor any of the others cure neuropathy. They treat symptoms. You have to get your diabetes under control too.

Anodyne therapy is available at a number of clinics across the country. To find the nearest, telephone the company or visit the Website listed below. Anodyne markets its apparatus both to health professionals and to consumers. The professional system is priced at $4,895, and the consumer system retails for $2,495. Medicare already accepts charges for in-clinic treatments, and full Part B coverage for purchase of the Anodyne Home System was pending as of 2004--the company says that it has appealed many Medicare refusals and won every one of them. For more details contact Anodyne Therapy LLC, 13570 Wright Circle, Tampa, Florida 33626; (800) 521-6664; Website <www.anodynetherapy.com>.

T.E.N.S., transcutaneous electrical stimulation (of the affected nerves) with a short jolt of electricity, appears to interrupt the transmission of pain signals and works for some people. Japanese researchers working for Nikken have used oscillating magnets with some success. Such oscillation manufactures electricity--a different approach to the same problem. The scientific basis for electrical/electromagnetic stimulation is unclear, but until neuropathy itself is better understood, "use what works for you" has to be the rule--there is no one correct symptom-relieving treatment for diabetic neuropathy.

Researchers were recently experimenting with aldose reductase inhibitors such as Sorbinil and Zenerstat, but these did not prove efficacious for neuropathy pain. And of course the search for new treatments goes on, with tests of antioxidants, nerve growth factors (rhNGF), blood vessel expanders, and various herbal/naturopathic substances. Most will fail, once serious clinicals are conducted.

Ever since Mesmer, the inventor of hypnotism, people have made various claims for the medical efficacy of magnets to treat various conditions. No scientific principle or beneficial effect from static magnetic fields has ever been discovered. Foot magnets to treat neuropathy and other conditions are advertised on the Internet and in consumer magazines. There is some statistical evidence for pain reduction (though, in data cited by the manufacturer, placebo users also showed unusually high improvement, so one wonders). We don't understand why magnets might work in some cases of neuropathy--but we don't understand the scientific basis of neuropathy pain either. The most experienced manufacturer of foot magnets is the Japanese firm, Nikken, whose U.S. offices are in Irvine, California, (949) 789-2000.

Again there is a lot of disagreement over effective treatments for neuropathy pain. Folks swear by their particular remedy. You need to find and use what works for you. Beware of extravagant claims for pill, technique, or machine; there are no miracle cures--though there are plenty of people ready to sell you one. Caution, caution, caution.

None of the pills and creams is as effective in bringing relief as is getting your blood sugars into good control and keeping them there. There is no cure without the achievement of good control, for without euglycemia you are pumping out the boat without patching the hole in its bottom. The International Diabetes Center's Website advises: "The best way to treat or prevent neuropathy in any area of the body is to control your blood glucose levels. Good glucose control may not reverse numbness or tingling, but it can slow or stop additional nerve damage. Good control can also bring on dramatic pain relief. Medications can be used to control the symptoms of painful neuropathy and gastroparesis (autonomic neuropathy of the digestive system) as well."

Consequences of Neuropathy

The main reason human beings have a pain reflex is that pain lets us know something is wrong in the affected area. If it hurts, we do something about it. With its biggest symptom being pain (when nothing is there) and diminished sensation/numbness (when something is present), neuropathy can seriously interfere with a diabetic's self-care, especially care of the feet. Circulatory problems from diabetes can lead to dry skin on the feet with the risk of ulcers and lesions. Lacking normal pain reflexes, the diabetic with neuropathy may not be aware his or her feet are in trouble. Even stepping on a tack may be pain free. This means otherwise treatable lesions go unnoticed and allowed to progress into severe infection, sometimes into gangrene itself. Amputation is a common result, and complications of diabetes account for the majority of nontraumatic amputations in the U.S. today. All diabetics need to inspect their feet frequently, but individuals with neuropathy need to be especially thorough because early detection of foot problems can be critical to saving the infected foot.

The linkage between dry feet and neuropathy is close. They frequently occur together; both are common symptoms of diabetes. To deal with the dryness, you may need a good diabetic foot cream--and note that these are thicker than conventional hand creams. Talk to your doctor or your podiatrist.

Other Coping Strategies

Although there are lots of variations, with the rule being "do what works for you," folks cope with neuropathy pain in a number of nonmedicinal ways. One individual, who reported burning feet at night, slept with her feet uncovered and a fan blowing cool air on them. Many others cushion aching feet with thick, seamless hikers' socks, especially those made of cotton or of manmade materials such as Thorlo.

Some folks report that exercise brings relief, however temporary. Others use meditation-based relaxation techniques to help them manage. Another approach followed by many is to wear high-quality, properly fitting athletic (walking) shoes with good support or support sandals such as Birkenstocks, along with the socks mentioned above. Your podiatrist can help you choose an appropriate brand and style--and appropriate footgear is a good idea for everyone with diabetes, whether you have neuropathy or not--listen to your podiatrist, not the salesman at the neighborhood discount shoe store.

Many people whose feet are affected by diabetic neuropathy are also dealing with circulatory/microvascular problems. Their ability to heal from otherwise minor cuts and scrapes is often seriously impaired, leading to a history of ulceration or even a partial amputation. Special therapeutic shoes, with custom inserts, or extra-depth shoes, or several other orthotic shoe modifications, are covered by Medicare as "durable medical equipment." Discuss this with your doctor.

New Research

Although many medicines are used for treatment of neuropathy's symptoms, not all are yet officially FDA-licensed for such use. However, doctors have wide leeway in such off-label prescribing, and several prescription medications have passed safety inspection--and are now being evaluated for their efficacy as neuropathy treatments.

New medications are also under investigation, some to treat symptoms and others that might someday treat the underlying cause, the demyelinating nerve damage. CenterWatch, a clinical trials listing service, lists many separate FDA-mandated clinical trials of new neuropathy medications under way in the United States on human subjects. One such study is of the drug memantine, already used for Alzheimer's and Parkinson's and currently under investigation for neuropathy. Many more studies are at the test tube stage or currently in animal trials.

Conclusion

Unexplained pain or abnormal sensation is a serious matter. It may indicate neuropathy, which may be from diabetes or some other condition; your doctor needs to determine its source promptly. Neuropathy is not an inevitable ramification of diabetes, and you shouldn't just grin and bear it. Different therapies and interventions bring relief to many diabetics. Keep the best blood glucose control you can, keep your doctor informed, and don't lose hope.

For Further Reading

A great deal of research is being done on this subject. Although most findings are published in professional research journals, World Wide Web searches on "neuropathy" reveal hundreds of timely listings, many linked to other sources. Here are a few Websites you might find worthwhile:
<www.niddk.nih.gov/health/diabetes/ndic.htm> The National Institute of Diabetes and Digestive and Kidney Diseases
<www.centerwatch.com> Center Watch; lots of trials under way
<www.intelihealth.com> InteliHealth Website, connected with Harvard; follow links for diabetes.
<www.cdc.gov/> Centers for Disease Control and Prevention
<www.diabetesmonitor.com/dr-00005.htm#neurop> Diabetes Monitor's neuropathy page
<www.parknicollet.com/Diabetes/> (International Diabetes Center's Home Page)
<www.mendosa.com/neuro.htm> (David Mendosa's review of current research in new neuropathy medications; this site also has links to a wealth of other useful information on diabetic neuropathy.)
<www.cymbalta.com> (Eli Lilly’s Cymbalta/duloxetine Website)
<www.lyrica.com> (Pfizer’s Lyrica/pregabalin Website)

Published Sources:
"Diabetic Neuropathy: Current Practice and Promising New Therapies," Interdisciplinary Medicine (March 1999), Vol. 4, No. 1.
"Taming the Pain of Nerve Disease," Diabetes Advisor (May/June 1999) Vol. 7, No. 3.
"New Treatments for Diabetic Neuropathy," by Keith R. Edwards, MD. Home Health Care Consultant (March 1999), Vol. 6, No. 3.
“Pathophysiology of Painful Neuropathy," by Mark Granberry, Suresh Baliga, and Vivian Fonseca. Practical Diabetology (June 1999), Vol. 18, No. 2.


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