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Diabetic Neuropathy (Nerve Damage) - An Update

Nerve damage or diabetic neuropathy resulting from chronically high blood glucose can be one of the most frustrating and debilitating complications of diabetes because of the pain, discomfort and disability it can cause, and because available treatments are not uniformly successful.

Some patients find some relief from this nerve damage or neuropathy by keeping blood sugars as closely controlled as possible, getting regular exercise and keeping their weight under control. Using non-narcotic pain relievers consistently throughout the day—rather than waiting until nighttime when symptoms can become more severe—also seems to help if pain is the major symptom. Surprisingly, clinicians have also found that certain antidepressants may be helpful and can take the edge off the pain of neuropathy.

Although pain or numbness in the legs or feet may be the most common complaint from people diagnosed with neuropathy, it is not the only symptom of this complication. Neuropathy can cause a host of different types of symptoms, depending on whether nerves in the legs, gastrointestinal tract, or elsewhere in the body are affected. If you have any of these symptoms, neuropathy may be the culprit:

Although physicians have found some medications and other treatments that help ease these symptoms in some people, prevention continues to be the key. "Hemoglobin A1C readings should ideally be at 7.0% or lower. Those that are consistently near or higher than 8% cause concern that any diabetes complication, including neuropathy, may develop," says John Hare, MD, Medical Director of Joslin Diabetes Center’s Affiliated Center's program. "The good news is that the Diabetes Control and Complications Trial shows that people who keep their blood sugars consistently in this healthful range can decrease their risk of nerve damage by more than 50%. Getting diabetes under better control also may help limit the amount of damage caused by neuropathy once it's developed."

If your healthcare provider has told you that symptoms you have been experiencing are a result of neuropathy, you certainly have many questions. The following are some answers that may be helpful to you as you battle this complication.

What are the different types of neuropathy?

There are three broad types of neuropathy: sensory, autonomic and motor:

Sensory neuropathy can lead to pain, numbness or tingling in the extremities and, ultimately, an inability to feel heat, cold, pain or any other sensation in affected areas. Autonomic neuropathy can lead to impotence in men, bladder neuropathy (which means the bladder is unable to empty completely), diabetic diarrhea, or bloated stomach. Motor neuropathy can lead to muscle weakness.

If you are diagnosed with neuropathy, your physician may use terms to describe the type that you have based on whether only one side of your body is affected (asymmetric) or both sides (symmetric). If only one kind of nerve is affected, your doctor may say you have mononeuropathy. If several nerves are affected, the term polyneuropathy may be used.

Other terms may be used based on what parts of the body are affected, including:

What is peripheral neuropathy and what causes it?

Peripheral neuropathy (more commonly called neuropathy) is a general term for diseases that cause damage to the nerves outside of the brain and spinal cord. While diabetes is a frequent cause of neuropathy, it is not the only cause. Nutritional deficiencies (B-12 and folate), chemical exposures, pressure on nerves, or medications (such as some of those used for chemotherapy or to treat AIDS) can also cause neuropathy.

Theories abound as to why exactly neuropathy occurs in people with diabetes. In general, diabetic neuropathy is thought to be a result of chronic nerve damage caused by high blood glucose. "There are many possible ways this might happen," says Dr. King. "Nerves are surrounded by a covering of cells, just like an electric wire is surrounded by insulation. The cells surrounding a nerve are called Schwann cells. One theory suggests that excess sugar circulating throughout the body interacts with an enzyme in the Schwann cells, called aldose reductase. Aldose reductase transforms the sugar into sorbitol, which in turn draws water into the Schwann cells, causing them to swell. This in turn pinches the nerves themselves, causing damage and in many cases pain. Unless the process is stopped and reversed, both the Schwann cells and the nerves they surround die."

Another theory is that certain intracellular metabolites, such as myoinositol, become depleted, leading to nerve damage. Still other theories hold that pathways such as the protein kinase C pathway, being studied by George King, MD, Director of Research and Head of the Section on Vascular Cell Biology and his colleagues at Joslin, are triggered by chronic high blood glucose, resulting in several diabetes complications, which might include neuropathy.

"Recent studies have suggested that decreased blood flow to the nerves can also contribute to the development of diabetic nerve disease," says Dr. King. There are multiple studies ongoing which are designed to improve blood flow to the nerves in diabetic animals and in patients. Two new categories of drugs being examined are called antioxidants and PKC inhibitors. Preliminary studies using these drugs have shown encouraging results in animal models of diabetes. Clinical trials are being planned and some are already in progress.

How is neuropathy diagnosed?

People may seek their healthcare provider’s help for treatment of pain, not knowing exactly what causes it. Men may come to the doctor concerned about a decreasing ability to have and maintain an erection. Increasingly frequent urinary tract infections may be another clue, as may be recurring diarrhea or constipation, or vomiting or symptoms resembling an ulcer. Fainting spells upon standing may indicate postural hypotension.

A physician may detect early signs of neuropathy. He or she may notice that knee and ankle jerk reflex tests show nerves aren't as responsive as normal, or may observe a dip in blood pressure when you go from a reclining to sitting position. These are signs that increased attention to blood glucose are warranted to try to limit further problems.

A variety of tests, including electromyography (a test that measures the response of muscles to electrical impulses) and nerve conduction studies (a study of the flow of electrical current through the nerves) combined with clinical observations may help a physician rule out other possible causes of pain and diagnose neuropathy. To diagnose Charcot foot fracture, the doctor may take an X-ray and possibly conduct a bone scan.

How is it treated?

Unfortunately, there are no miracle cures or treatments for neuropathy, although a variety of treatments are often helpful. There is no way to heal or replace nerves that have been damaged.

The most important thing someone who has neuropathy can do is keep their blood glucose levels as close to the target goal as possible, exercise regularly, and make sure his or her weight is as close to what it should be as possible. This will help keep blood glucose closer to normal and limit the damage high blood glucose can cause to nerves. Exercise will have the added benefit of keeping muscles that may be weakened by decreasing nerve activity to remain strong and toned. Christopher Gibbons, MD, of Joslin, says he finds that patients with painful neuropathy say the pain seems less severe if they get some simple exercise regularly.

Patients with painful neuropathy will try almost any kind of pain reliever their physicians will give them. "One can try a variety of non-narcotic pain killers," says Dr. Gibbons. "But one should stay away from the more powerful narcotics, which do not work very well for neuropathy, but will lead to addiction."

Dr. Gibbons recommends acetaminophen (Tylenol®), aspirin and ibuprofen (Motrin® Advil®, etc.) first. Pain medicines are best used regularly throughout the day, rather than waiting for pain to become severe. At that point, pain medicines are less able to stem the tide, says Dr. Gibbons. Some physicians recommend creams that contain capsaicin, an extract of the hot capsicum pepper (which includes red, cayenne and tabasco peppers) and can be rubbed on the skin over the pain. It is believed in some circumstances that these creams block pain signals, although they do not work for everyone—occasionally, they may even worsen the pain in some patients or cause other adverse effects, like eye or skin irritation. Be sure to check with your doctor before trying such products and follow application instructions carefully. Capsaicin, which has been approved by the Food and Drug Administration for treating pain, is available in over-the-counter topical salves that include ArthriCare® and Zostrix®.

Certain antidepressants also seem to be particularly helpful for pain, says Dr. Gibbons. Amitriptyline (Elavil®), desipramine (Norpramin®) or imipramine (Tofranil®) are members of the tricyclic antidepressant category of drugs. These medications are not prescribed because the patient is depressed,  "although having constant pain for months can be depressing," notes Dr. Gibbons. "Rather, it seems that the medications block the pain. Patients take them at night, and they have the effect of helping patients tune the pain out. When I prescribe them to patients, I explain that it's kind of like having a full bladder. If you aren't doing anything, you notice the full bladder and you feel the need to go to the bathroom right away. But if you're engrossed in a TV show, you don't notice it as much and can go for quite a while before going to the bathroom. These anti-depressants have largely the same effect on pain, helping patients notice it less. Because the pain is usually worse at night, patients take the medication at night and it seems to help them sleep. It also helps them with the depression and insomnia they may be experiencing as a result of the neuropathy."

"Antidepressants can take several weeks to become effective, so I tell patients to give it a month before deciding whether it is helpful or not," says Dr. Gibbons. "These drugs can also cause dry mouth, which most patients find not to be much of a problem." 

Other types of drugs that sometimes help are anti-convulsants such as phenytoin (Dilantin®), carbamazepine (Tegretol®) or gabapentin (Neurontin®). Drugs such as mexiletine (Mexitil®) normally used to treat irregular heart rhythm sometimes relieve neuropathy pain. Drugs like metaxalone (Skelaxin®) that generally depress the central nervous system can help reduce muscle pain. All of these drugs, however, can have unpleasant side effects such as dizziness or confusion when taken in large doses, especially by elderly patients.

Many patients will ask their physician about the value of nutritional supplements or vitamins to ease pain. "If the neuropathy is caused by a vitamin deficiency, such as a B vitamin deficiency, taking B6 or B12 will help," notes Dr. Gibbons. "But if you're body is not deficient in these B vitamins, the vitamins will just go down the drain in your urine. You'll notice that your urine is a very bright yellow . . .  but the treatment probably won't do you any harm. As for other nutritional supplements or vitamin treatments, there isn't anything that is widely accepted as being useful, unfortunately. But other vitamins that are not so easily passed through the urine can lead to vitamin toxicity. So you need to be careful that you aren't taking too much of any vitamin supplement in the distant hope of easing the pain."

Some patients have experienced success will other forms of pain management, such as biofeedback, meditation, or acupuncture. "I don't discourage a person from trying any safe, non-drug approach to pain relief," says Dr. Gibbons. "What may not work for one person may work really well for someone else."

Some patients may remember a lot of talk in the late 1980s and early 1990s about a new class of drugs called aldose reductase inhibitors, which were thought to be a significant breakthrough in treating some types of neuropathy. "Unfortunately, to date none of these drugs has proven to be sufficiently effective and side-effects have been a concern. As a result none have come to market to treat neuropathy yet, although companies are still working to develop them," says Dr. Gibbons.

Treating gastroparesis
For gastroparesis, in which the stomach is not emptying properly, physicians at Joslin may prescribe metoclopramide (Reglan®), which will help the stomach push food and get it through the rest of the digestive process. These may be used in conjunction with sucralfate (Carafate®), which "helps to sop up extra acid that may be sitting in the stomach," Dr. Gibbons says.

Treating bladder neuropathy
For those experiencing bladder neuropathy, which results in the bladder never completely emptying, bethanechol (Urecholine®) may be prescribed. "This is a urine propellant that helps to keep the bladder clear," says Dr. Gibbons. "Because patients with this problem will be more likely to develop frequent urinary tract infections, the physician may also prescribe chronic antibiotic therapy to try and keep the bacterial count in the bladder and urinary tract at a manageable level."

Treating impotence
Impotence in men that is a result neuropathy or blood vessel damage (versus psychological causes or due to medications such as anti-depressants or blood pressure medication) can be treated using certain drugs that are either inserted into the end of the penis or injected to cause an erection before intercourse. Vacuum devices that enable an erection to be achieved or a surgically implanted prosthesis are also options to be explored with a physician.

There are other drugs, such as Cialis, Levitra®, and Viagra®, that may be an option, although patients should be sure to check closely with their physician before taking the drug. People with diabetes are more prone to heart and blood vessel disease than non-diabetics. The use of these drugs may lead to the resumption of sexual activity in individuals with underlying cardiovascular disease (diagnosed or undiagnosed), so such use should be reviewed and approved by a physician. Also, the use of these drugs  in combination with nitroglycerine tablets (a treatment for acute heart problems such as angina or heart attack) has led to several reported deaths. Finally, there is an unproven suspicion that usage of these drugs may also affect retinal circulation (in addition to its known side effects).

Treating postural hypotension
Patients with postural hypotension may be prescribed certain blood pressure raising medications or may benefit from support stockings to prevent pooling of blood in the legs. For patients with diabetes who also have high blood pressure, the process of balancing blood pressure lowering medications with medications that will keep blood pressure from dipping too low when sitting up after reclining can be particularly tricky, and may require several adjustments to fine-tune.

Treating Charcot damage
Charcot damage is addressed by avoiding putting any weight on the foot while it heals. The foot is usually put into a cast for a period of weeks to limit damage. Later, the patient wears special shoes. Surgery may be needed to restore a more normal shape to the foot.

How can further problems be avoided?

One of the major issues with neuropathy, particularly sensory neuropathy, is that eventually the affected nerves die, and the patient experiences a complete loss of sensation in the area. For this reason, if you have developed neuropathy in your feet and legs, you need to check your feet every day for cuts and other problems that you may no longer feel. You need to make sure your shoes are in excellent condition and don't have pebbles or rough spots in them that could damage feet without your knowing. If you have neuropathy, you should not use heating pads or electric blankets because you could seriously burn yourself without knowing it. You should be especially careful when taking baths to ensure that the water is not too hot, as it would be relatively easy to scald your feet or legs if they have become desensitized to pain.

When will the pain end?

"There's no easy answer to the question, 'When will the pain end?'" notes Dr. Gibbons. "Maybe if a patient gets their blood sugars under good control, that will be enough to ease the pain. If it doesn't, perhaps a daily regimen of Tylenol every few hours plus an anti-depressant at night and regular exercise every day will make the pain manageable. It can take up to two years for the pain of neuropathy, which is caused by ongoing damage to the nerve, to be replaced by the numbness that occurs when the nerve cells are more severely damaged. Our goal in the meantime is to identify ways to help patients manage the pain and discomfort of neuropathy and to help patients lead as normal a life as possible despite the pain or other side-effects caused by this complication."

Page last updated: November 26, 2014