Editor's Note: We get many questions about treatments for painful neuropathy. We invited Aaron Vinik, MD, a renowned neuropathy expert, to detail various treatments for neuropathy.

The symptom for chronic, painful, diabetic neuropathy is pain persisting for more than six months. Neuropathy can normally be controlled with stabilization of blood glucose. If neuropathy cannot be controlled, however, there are two types of neuropathy pain that you might experience: C-fiber type pain and A-delta type pain. People with long-standing type 1 and type 2 diabetes are susceptible to both types of pain, but people with newly diagnosed diabetes may have an acute form of C-fiber type pain. Different therapies exist to treat each type of pain.

I. C-fiber type pain is described as burning pain that worsens at night, causing insomnia, weight loss, anxiety and depression. With C-fiber type pain, the patient often complains that the slightest touch is considered painful. For this reason, people with C-fiber type pain do not like bedclothes to be in contact with the skin, nor do they like the hairs of the skin to be disturbed. There have been a number of trials using a host of different medications in the attempt to relieve these symptoms.

• Capsaicin - Topical application of capsaicin three times a day may be helpful. The drug needs to be applied with gloves, covered with saran, and users should avoid exposure to the genitals and other mucus membranes.
• Clonidine - Clinical trials have shown that after about one week, you can determine if clonidine is working.
• Neurontin - Neurontin relieved pain in 75 percent of patients with a 40 percent reduction in pain, compared with the placebo that relieved pain in 50 percent of the patients with a 20 percent reduction. This translates to an improved mood, less anger and hostility, and an enhanced quality of life. The most commonly encountered side effects are dizziness and confusion.
• Carbamazepine - Several double-blind, placebo-controlled studies have demonstrated carbamazepine to be effective in the management of pain in diabetic neuropathy. Toxic side effects may limit its use in some patients, and it is not safe for people with diabetes to take this drug for long periods of time.
• Dilantin - Dilantin has long been used in the treatment of painful neuropathies, however, double-blind studies have not demonstrated a therapeutic benefit using Dilantin compared to a placebo. Also, its ability to suppress insulin secretion has resulted in the precipitation of diabetic coma.
• Antidepressants - Amitryptylline, nortryptylline and imipramine may also be helpful. They are the best studied of all the agents used for pain, but have demonstrated major side effects, including drowsiness, lethargy, dry mouth, blurred vision and urinary retention (amitryptylline). Nortryptylline may be better tolerated in the elderly, but urinary retention may be avoided with imipramine. Relief of the pain does not necessarily correspond with relief of depression.

II. A-Delta type pain is a more deep-seated, gnawing, toothache-type pain which often does not respond to the treatment measures used for C-fiber type pain. A-delta type pain feels like wearing a pair of shoes one size too small. Intravenous insulin infusion administered throughout the day is often helpful for patients who suffer from this type of pain. Standard diabetes treatments, including insulin and oral hypoglycemic agents, are not changed and the regular meal plan is followed. A reduction in pain usually occurs within 48 to 72 hours, and the insulin infusion can then be discontinued. If a relapse in pain occurs, the infusion can be repeated. If these measures fail, however, there are several treatments available that may abolish the pain.

• Lidocaine - When given by slow infusion, 5 mg/kg over 30 minutes, lidocaine has been shown to provide relief of intractable pain for 3 to 21 days. This form of therapy may be of most use in self-limited forms of neuropathy, which occur when one nerve is suddenly deprived of its blood supply. If successful, therapy can be continued with oral mexiletine in dosages of 10 mg/kg per day.
• Tramadol and Dextromethorphan - When treatment at the peripheral level has failed, the next step is at the spinal level. Tramadol binds to the m-receptors while dextromethorphan targets and blocks the NMDA receptor, providing pain relief. Doses of the medication should be taken in 30 to 150 mg.
• Transcutaneous Nerve Stimulation - This benign therapy for painful neuropathy involves moving around electrodes to identify sensitive areas and obtain maximum relief.
• Analgesics - Rarely of much benefit in the treatment of painful neuropathy, they may be of some use on a short-term basis for some of the syndromes such as painful, diabetic third nerve paralysis. Use of narcotics in the setting of pain is generally avoided because of the risk of addiction.
• Calcitonin - In a small, placebo-controlled study, 10 patients with diabetic neuropathy were treated with 100 IU of calcitonin per day. About 39 percent of the patients had nearly complete relief of symptoms after two weeks of treatment. Similar results, however, have been achieved with a placebo in other studies.

Experimental Studies and Treatments

There are several reports on trials of powerful antioxidants that have been successful in Europe. The Aladdin study showed that intravenous administration of alpha-lipoic acid relieved pain. Another recently completed study on the use of nerve growth factor has shown that patients have improvements in neuropathy pain. This study, conducted throughout the world, is about to end, and the FDA has fast tracked the approval of nerve growth factor, so we can anticipate its availability for clinical use in the near future.

There are now a number of compounds being investigated for their possible use as pain-relieving drugs in diabetic neuropathy. In addition to nerve growth factor, there are also Neurotrophin 3, alpha-lipoic acid, Tramadol, Prosaptide, Timcodar, Oxycontin and ABT-594. These drugs are in phase 2 trials in the United States at a limited number of centers, and we have yet to learn of their efficacy.

I also strongly encourage exercise, and endorse the use of massage to relieve secondary muscle spasm that occurs with neuropathy pain. Exercise, by releasing endogenous endorphins, makes people feel better and makes pain more tolerable. There are institutions that use marijuana, and it does relieve some intractable pain.

Aaron Vinik, MD, PhD, FCP, FACP
Diabetes Institute, Eastern Virginia Medical School
Norfolk, Virginia