Diabetes Forecast

Treating Nerve Pain

Neuropathy is excruciating for some people. Here’s why—and how you can treat it.

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The symptoms can be so subtle you may not notice them for months, or even years: patches of numbness or tingling, usually in the toes or feet. For some, the numbness can turn to mild irritation and then sharp pain or burning.

Those symptoms are caused by nerve damage, or neuropathy, one of the most common complications of diabetes. Half of all people with diabetes will eventually develop some form of neuropathy. Peripheral neuropathy, which affects the nerves that transmit feelings of touch from your extremities to the brain, is the biggest threat. People who experience a loss of sensation or numbness are at higher risk for injuries and foot wounds that won’t heal. Other nerves—the autonomic nerves that keep your heart beating, for example, or motor nerves that control movement—are also vulnerable, though their symptoms may take longer to develop.

“Why some develop painful neuropathy and others don’t, we don’t know,” says Gordon Smith, MD, FAAN, a neurologist at the University of Utah.

Researchers also aren’t sure why some damaged nerve cells send no signals (numbness) and others report pain when they shouldn’t. “Neuropathy has two different impacts,” Smith says. Nerves either stop signaling, or they signal way too much and in the wrong ways.

The longer you’ve had diabetes, the greater the likelihood of nerve damage. People who have lived with the disease for more than 25 years are at the greatest risk, according to the National Institute of Diabetes and Digestive and Kidney Diseases. For those who develop painful neuropathy, there are two major questions: Why do I have this? And how can I treat it?

Cutting the Cord

The hallmark of peripheral neuropathy is damage to the connections that link the feet and hands to the brain—single nerve cells that can stretch out for several feet, from the spine to the tips of your toes or fingers. “There are a few dozen different types of neuropathy, but by far the most common is this injury to the longest nerves,” says Bruce Perkins, MD, a researcher specializing in neuropathy at Toronto General Research Institute in Canada.

Doctors say people with diabetes are particularly affected by neuropathy for several reasons. First, nerve cells are more vulnerable than most other cells because they don’t need insulin to take up glucose, giving them greater exposure to high blood glucose. And the ones that connect your toes to your brain may be the most vulnerable of all.

If you think of the nerves as telephone wires stretching from coast to coast, it’s easy to see how a cut or downed telephone pole anywhere along the line could disrupt the signal. “The nerves that are the wires from the spine to the organs and muscles and skin are very fragile,” says Perkins. “Having high blood sugar messes up those cells quite easily.”

The second reason has to do with circulation. All nerve cells need a constant flow of blood to keep working. People with diabetes often have damage or dysfunction in the tiny blood vessels that nourish individual cells, interrupting blood flow and “starving” the nerves.

And finally, there’s the challenging environment at the end of the line. The nerves that report sensations of touch and heat back to your brain end just under the skin. As skin cells die, the body replaces them, constantly renewing its outermost layer: You get a whole new skin approximately once a month.

The tips of your nerve cells—there are about 1,000 per square inch of skin—need to keep up.  For people with diabetes, that regrowth process doesn’t work the way it should. Studies have shown that diabetes causes nerve cells to die faster while simultaneously slowing their regrowth. “You can think of it as a double whammy,” Smith says.

Fighting Pain

Treatment for painful neuropathy falls into two approaches: drugs and other treatments that deal with the symptoms, and efforts to tackle the underlying causes of neuropathy, including diabetes, says Brian Callaghan, MD, a neurologist at the University of Michigan in Ann Arbor.


Doctors rely on a number of ways to treat neuropathic pain. Those include pills developed to treat epileptic seizures and depression medications that work on central pathways in the brain, where the signals from the nerves have to go.

Products such as lidocaine creams or patches may also help relieve the pain. Doctors sometimes prescribe opioids in pill or cream form, which contain the same active ingredients as morphine. “That’s a medication of last resort because of a high risk of side effects, including addiction,” says Smith.

Experimental Treatments

Electrical stimulation devices that send a pulse of electricity through the skin to stimulate the nerves have been studied. None have been proven to relieve neuropathic pain, but researchers say more data is needed before they can be dismissed outright. Acupuncture, a nontraditional treatment, also hasn’t been proven in clinical trials, but some patients report feeling better afterward.


One approach doctors are looking at uses capsaicin, the chemical responsible for the burning sensation you get from eating spicy foods. There’s one capsaicin treatment approved by the Food and Drug Administration for neuropathy, and while doctors may prescribe it for diabetic neuropathy, its usefulness is still to be determined. Sold under the trademark Qutenza, the method—approved by the FDA to treat a different kind of nerve pain—uses a large dose of capsaicin to get the nerves overexcited. Like a man shouting himself hoarse, the nerves temporarily lose their “voice” and can’t send pain signals to the brain for a while, in part because they’ve retracted from the surface of the skin. “It causes pain and depletes pain signaling,” says Smith. “Afterward, you can go for months without nerves firing.” The dose is applied by a doctor, who uses a painkiller so you can’t actually feel the burn. One treatment is often enough to achieve an effect. Smith is also using capsaicin in experiments to measure nerve regeneration in people undergoing gastric bypass surgery to see if weight loss has an effect on nerve function and growth.


Another unusual approach comes from Texas Tech University Health Sciences Center researcher Munmun Chattopadhyay, PhD. With the help of a grant from the American Diabetes Association, she’s using modified herpes simplex viruses—the kind that give you cold sores—to treat neuropathic pain. “If we can find a treatment at the pain phase, maybe we can delay or prevent some of the neuropathy,” Chattopadhyay says.

Between breakouts, the herpes virus hides in nerve cells, making it a possible delivery vehicle for pain-dampening chemicals. Before injecting the virus into the feet of rats with an experimental form of type 1 diabetes, Chattopadhyay modifies the virus in two important ways: First, she turns off the genes that cause the virus to multiply, preventing it from causing cold sores. Then Chattopadhyay and colleagues add genes that instruct it to produce a chemical that blocks the nerve from sending signals.

Chattopadhyay’s experiments are still only in rats, though. For now, all of the methods approved for use in humans are limited: They work in some patients but not others, or need different dosages to take effect. It’s important to work with your health care team to find the right combination for you. “If someone has painful neuropathy, they have to have realistic expectations—none of these treatments takes away pain altogether,” says Perkins. “They tend to take the edge off so people can get better sleep or function better.”

Searching for a Cure

Curing neuropathy, rather than just treating its symptoms, is even trickier. “There have been decades of research on therapies that might heal nerves, and they’ve mostly been failures,” says Perkins.

Neuropathy moves slowly, and the first symptoms—numbness in the toes, for example—might be hard to notice in the beginning. The effectiveness of treatments that might slow or reverse such subtle early effects are hard to measure in studies that last just a year or two.  “To see the impact of interventions you need a really long-term study,” says Osama Hamdy, MD, PhD, director of the Joslin Diabetes Center’s Obesity Program.

But there are some things scientists do know. For people with type 1, controlling blood glucose levels may delay the development of neuropathy. The Diabetes Control and Complications Trial, a 10-year look at people with type 1, showed that intensive insulin therapy reduced the risk of neuropathy by 65 percent, making tight blood glucose control the most effective nerve pain–prevention treatment for people with type 1.

Smith says early-stage drug trials are also looking at drugs that could slow or prevent nerve degeneration. The Foundation for Peripheral Neuropathy is gathering DNA from patients around the country to look at whether people who develop painful neuropathy are genetically different from people without nerve pain.

Other scientists are scanning the brains of patients with painful neuropathy to see if there’s something that sets them apart. “The nerves are sending signals that would be perceived as pain,” Smith says. “Maybe there are changes in how the spinal cord and brain process the nerves’ signals.”

Experts say a drug that reverses the effects of neuropathy could be a long way off—but there are lots of reasons to be optimistic. “We’re developing new treatments for nerve pain and starting to understand the mechanisms of neuropathy,” says Callaghan. “There is a lot of active research and we’re learning more and more. The future is bright, even if we don’t have all the information we’d like.”

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