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While all the specific causes of neuropathy are not fully understood, medical professionals and researchers agree the most effective treatment for neuropathy is the stabilization of blood glucose levels.
This is strongly supported by the results of the Diabetes Control and Complications Trial (DCCT) which reported a 60 percent reduction in the risk of the development and progression of neuropathy with tightly controlled blood glucose levels.
High Blood Sugars are the Main Culprit
Hyperglycemia (high blood sugar) can worsen neuropathy in several ways. Hyperglycemia is known to cause excess blood glucose to bond to proteins in the body. This can lead to direct damage to nerves, as well as narrowing of the arteries which diminishes blood flow and oxygen delivery, causing pain and tissue death. Elevated blood glucose levels have also been demonstrated to decrease levels of magnesium in the body, contributing to vascular constriction, impaired blood flow and insulin resistance. Finally, studies of rats that receive beta cell implants and humans who receive pancreas transplants indicate that normalization of BG levels clearly halts the progression of neuropathy.
There are several drugs available for treating the pain of neuropathy. These include antidepressants and anticonvulsants, as well as capsaicin, a topical cream derived from cayenne pepper. The optimal drug therapy depends upon proper diagnosis.
Researcher and leading diabetic neuropathy specialist, Aaron Vinik, MD, PhD, recommends that near normal (i.e. nondiabetic) BGs and HbA1c levels should be achieved in every patient with neuropathy. If these are within a desirable range and neuropathy does not improve, additional therapy should be pursued.
He notes that controlling pain is one of the most difficult management issues in diabetic neuropathy, but presents a step wise approach to pain control.
Simple measures are tried first. If these fail patients are divided by the type of pain they experience, c-fiber pain or A delta-fiber pains, and receive therapies that are quite different. C-fiber pains are characterized by burning and dysesthesia (hypersensitivity to gentle stimulation). A delta-fiber pain is characterized by deep seated, gnawing, toothache-type pain.
The following information on some of the available neuropathy treatments was presented by Vinik at the 45th Annual Advanced Postgraduate Course this past January. Note that all people respond differently to different treatments, so consult with your doctor before making any changes to your own treatment regimen.
According to Vinik, analgesics, or common pain relievers, are rarely beneficial in the treatment of painful neuropathy, but can be helpful on a short-term basis. He also notes that narcotic pain relievers are generally avoided because of the risk of addiction.
Clonidine is an antihypertensive agent that works by controlling nerve impulses along certain nerve pathways. It relaxes blood vessels allowing blood to pass through more easily. Some mediation of c-fiber pain may also be overcome with clonidine (or phentolamine).
If patients respond to a clinical trial of phentolamine (another blood vessel expanding medication), Vinik starts a trial of topical clonidine for one week. According to Vinik the likelihood of success or failure will usually present itself within this time frame.
C-fiber pain often responds to capsaicin. Capsaicin, extracted from chili pepper, is used in the form of a topical cream (such as Zostrix-HP) containing a 0.075 percent concentration of capsaicin. It needs to be applied three to four times a day.
Capsaicin is thought to work either by depleting "substance P," a neurotransmitter which is fundamental to the body's pain mechanism, or by acting as a counter-irritant, causing an initial increase and then decrease of pain by over-stimulating certain nerves. (Diabetes Forecast, June 1992)
This may explain why some individuals experience an initial exacerbation in symptoms followed by relief in two to three weeks. While this usually fades after a week or two, it appears to deter some people from continuing their treatment.
Capsaicin, however, is rather expensive. To avoid these costs Vinik recommends making your own capsaicin-like cream by mixing three teaspoons of cayenne pepper in a jar of cold cream.
If you decide to use either type of cream, special care must be taken when applying it to prevent irritation to other parts of the body. Users should wear gloves and apply only a thin layer of the cream. If it is applied too thick, it may dry and chip off creating a powder that can irritate the mucous membranes of the eyes, nose, mouth and lungs.
The use of Vinik's home version of capsaicin provided the foundation for a memorable moment for the doctor. "Perhaps the worst day of my life was when a six foot four inch, 240 pound man came into my office, grabbed my collar and told me he was going to kill me," remembers Vinik.
The man asked if Vinik had recommended that his wife put the cream on her feet. Vinik replied that he had when the man furthered his question with, "And you didn't tell her to wash her hands before we had sex?"
"The moral of this story is to remember to always use plastic gloves," says Vinik. Diabetics require support from their loved ones, but as this example shows, everyone has their threshold.
Lidocaine, an anesthetic that can be delivered in a number of ways, may also be helpful for both types of neuropathic pain. Vinik notes that, when given by slow infusion (5 mg per kg of body weight over 30 minutes), it can provide relief of pain that is especially difficult to manage for three to 21 days. If it is successful, therapy can be continued with oral mexiletine (a medication primarily used to correct irregular heart beats) in a dose of less than 10 mg per kg of body weight each day.
Both of these drugs reduce pain by targeting the hyperexcitability of nerve endings often found in neuropathy.
Carbamezapine and Neurontin
According to Vinik, several clinical studies have shown that carbamezapine, an antiseizure medication also used for certain types of pain relief, is effective in managing neuropathic pain. However, toxic side effects limit its use in some patients.
Neurontin is another anticonvulsant which may help relieve pain. Vinik notes that while its "mechanism (of action) is not well understood," it "holds promise as an analgesic agent in painful neuropathy."
Salmon calcitonin nasal spray, commonly used to prevent bone loss in women with post menopausal women with osteoporosis, has also been shown to help women with painful neuropathy. Vinik notes that in one study, 40 percent of patients with painful diabetic neuropathy who were treated with 100 mg of calcitonin per day had near relief of symptoms. The improvement was seen after only two weeks of treatment.
Tramadol and Dextromethorphan
When the above measures to control "peripheral level" pain fail, Vinik recommends treatment should be directed at the "spinal level." Tramadol, a pain reliever similar to a narcotic that is used to relieve pain after surgery, may be effective, as well as dextromethorphan, a medicine for relieving coughs from cold and flu that also has pain relieving effects.
Several antidepressant medications have also proven effective in managing neuropathic pain. It is believed that their central action accentuates the effects of neurotransmitters and their reactions with pain transmitting cells in the spinal cord.
The ones most commonly used include desipramine (Norpramin), amitriptyline (Elavil) and fluoxetine (Prozac). In a study by the National Institutes of Health, desipramine and amitriptyline were found to reduce pain for both depressed and non-depressed patients with neuropathy, while fluoxetine (Prozac) only helped depressed patients. (The New England Journal of Medicine, May, 1992)
Several other nonpharmacological options are also available to control neuropathic pain. Alan Marcus, MD, says that two of the most effective treatments include normalizing cholesterol and magnesium levels in the body. Because adequate blood flow and oxygen delivery is important for maintaining healthy nerve tissue, normalizing cholesterol levels to help keep the circulatory system free of obstruction is extremely important.
Given the connection between magnesium deficiency, diabetes, atherosclerosis and hypertension, magnesium supplements are often recommended for the treatment and prevention of neuropathy. It has also been shown to play an important role in glucose metabolism which may in turn help in blood glucose control.
A blood test is recommended to determine if a patient has a magnesium deficiency. (It should be noted, however, that magnesium is not recommended for patients with kidney failure.)
Other vitamin and mineral supplements may also prove helpful. These include vitamin B, myo-inositol, vitamin E and other antioxidants. Vitamin B deficiency is known to be a cause of neuropathy and may aggravate the condition once it has begun.
Myo-inositol is a B vitamin complex, and myo-inositol deficiency has been connected to diabetes in animal studies (Clinical Diabetes, July-August 1991). Vinik recommends brewer's yeast as a rich source of myo-inositol that can be safely taken in doses up to 3,000 mg daily.
Vitamin E improves circulation and oxygen utilization and may help to repair nerve damage as well. Dr. M.G. Traber discovered that patients with neuropathy had significantly less vitamin E in their tissues than people with other types of neurological disorders (The New England Journal of Medicine, 1987). Marcus recommends 400 mgs of vitamin E daily for the treatment of neuropathy.
In addition, a study of the effect of gamma linoleic acid on diabetic neuropathy suggests that supplements are beneficial to nerve function (Lancet, December 1991). A number of readers have reported benefits from gamma linoleic acid, preferably in the form of borage oil capsules found in many health food stores.
Both vitamin E and gamma linoleic acid are antioxidants. Antioxidants work by neutralizing harmful "free radicals" (activated oxygen atoms) which have been found to damage cells and impair the immune system.
Recommendations about taking B or other vitamins should always be made on a case-by-case basis by a qualified medical professional.
Other Ways to Relieve the Pain
Vinik reports that short-term insulin infusion has been found to ease the pain of neuropathy. It is usually most useful for the deep-seated, gnawing pain associated with delta-fiber pain as it is often unaffected by the above measures.
The infusion is administered by intravenous drip for 48 to 78 hours, using 0.8-1.0 units of insulin per hour. This treatment was discovered accidentally, and while its effectiveness is not understood, it is appears not to be related to blood glucose stabilization.
Other recommendations for improving the health of the nervous and circulatory systems include adequate exercise, massage and eliminating alcohol and tobacco use.
For muscle pain, the most effective form of treatment appears to be stretching exercises. Many patients show significant improvement without the use of muscle relaxants or anti-inflammatory drugs.
Before trying new treatments for neuropathy, consult your physician. Not all remedies are recommended for all people. Changes in your treatment regimen should be made with the input of a trained health care professional.
Mar 1, 1998