Peripheral neuropathy results from injury to the peripheral nerves in the body. These nerves carry signals between the central nervous system (the brain and spinal column) and the muscles, skin, and internal organs. When peripheral neuropathy first develops, people often report a tingling or prickling in the toes, although it can also start in the fingers. Over time, the tingling gradually spreads up the feet or hands and worsens into a burning, shooting, and/or throbbing pain. People who have severe peripheral neuropathy may experience extreme pain and may have difficulty walking, sometimes requiring the assistance of a cane or wheelchair to move around.
People who have peripheral neuropathy usually experience symptoms on both sides of their bodies. In other words, peripheral neuropathy almost always occurs in both feet and/or both hands. The sensations can be either constant or periodic. Sometimes they may not be noticeable, while at other times they may be extremely bothersome.
Not only can peripheral neuropathy be physically painful, it can also have a profound effect on quality of life. The natural instinct to avoid or reduce pain can prevent people from going about their regular day-to-day activities, whether it be going up and down stairs, visiting with family or friends, or going to work. This can cause a great deal of anxiety and can lead to serious depression—serious emotional problems that can make life seem altogether frustrating.
What causes peripheral neuropathy?
There are several possible causes of peripheral neuropathy. Direct injury, such as a broken bone or a severe burn, can cause damage to peripheral nerves. Certain diseases, such as diabetes, arthritis, or lupus, can also result in nerve damage. A lack of essential vitamins and minerals, particular vitamins B12 and E, can contribute to nerve damage. Conversely, taking too much vitamin B6 (more than 200 mg a day) can actually cause this condition.
HIV itself has also been shown to cause nerve damage, usually in people with seriously suppressed immune systems. Though researchers aren’t yet certain how HIV causes nerve or brain injury, many believe it is due to chronic immune system inflammation due to HIV replication.
In 2009, researchers from the CHARTER study reported that they were able to find symptoms of peripheral neuropathy in a significant percentage of older HIV-positive individuals—even in people without other risk factors. The degree of peripheral neuropathy was very mild in most people, and in fact most were unaware that they had sustained any nerve damage.
Moderate to severe peripheral neuropathy in people living with HIV is a usually side effect of certain medications, including those used to treat HIV and certain AIDS-related infection. These drugs can damage peripheral nerves and eventually lead to symptoms of neuropathy.
The most likely reason why certain HIV drugs cause peripheral neuropathy is that they can damage mitochondria—the genetic powerhouses inside cells that help convert nutrients into energy that our cells need. Too much mitochondrial damage, researchers believe, can lead to nerve damage and peripheral neuropathy.
Some of the HIV/AIDS drugs that can cause peripheral neuropathy include:
Hivid (zalcitabine) – no longer sold
Videx; Videx EC (didanosine)
Nydrazid (isoniazid) – for the prevention and treatment of tuberculosis (TB)
Oncovin (vincristine) or Velban (vincristine) – for the treatment of Kaposi’s sarcoma (KS)
Myambutol (ethambutol) – for the treatment of MAC and other bacterial infections
Flagyl (metronidazole) – for the treatment of amoebas and parasitic infections
Zyvox (linezolid) – for the treatment of bacterial infections
dapsone – for the treatment of Pneumocystis jiroveci pneumonia (PCP) and other infections
While peripheral neuropathy is a common side effect of these drugs, this does not mean that all people who take them will experience nerve damage or develop symptoms of neuropathy. It’s possible that people who combine these drugs—such as Zerit and Videx, two nucleoside reverse transcriptase inhibitors (NRTIs) that are no longer routinely used together—are at a greater risk of experiencing neuropathy or developing more severe and painful symptoms. Similarly, people who use these HIV medications with other drugs known to cause peripheral neuropathy may also be at an increased risk of this side effect. The risk of peripheral neuropathy may be higher still if these medications are used in people with a history of neuropathy, diabetes, heavy alcohol consumption, poor nutrition, and/or older age.
What are the symptoms of peripheral neuropathy?
Because peripheral neuropathy is not the only nerve-related problem that can occur in HIV-positive people, it’s important that you report any noticeable symptoms to your health care provider. Once you and your doctor have determined the source of these symptoms, you can work together to figure out what to do about it.
The symptoms of peripheral neuropathy usually occur in the feet and/or hands:
- Numbness/insensitivity to pain or temperature
- Extreme sensitivity to touch
- Tingling, prickling, or burning sensation
- Sharp pain/cramping
- Loss of balance/coordination
- Loss of reflexes (your doctor can check these)
- Muscle weakness
- Noticeable changes in the way you walk
Other symptoms of nerve damage that you’ll want to report to your doctor include:
- Noticeable increase in the number of times you need to urinate during the day and at night
- Difficulty walking up and down stairs
- Frequent stumbling or falls
- Erectile dysfunction
Should I stop my medicines that are causing the neuropathy?
Generally speaking, the best way to manage peripheral neuropathy is to stop (or switch) any medications that may be causing the problem. For example, if you are taking an antiretroviral drug regimen that contains Zerit, the first approach should be to switch the Zerit for another NRTI that is less likely to cause peripheral neuropathy (options might include Retrovir [zidovudine], Viread [tenofovir], or Ziagen [abacavir]). Of course, you should discuss this option with your health care provider—do not attempt to stop any of your medications or to switch them without first checking in with your doctor.
It can sometimes take a few weeks or months for symptoms of peripheral neuropathy to improve after stopping an offending drug. In some cases, symptoms can worsen before they get better.
What about medications to treat peripheral neuropathy?
Other than stopping neuropathy-causing drugs—which isn’t always possible for people with limited HIV treatment options or in need of other medications for certain illnesses—managing peripheral neuropathy can be a challenge. A number of treatments have been used over the years, and are still prescribed, to treat the painful symptoms of peripheral neuropathy (reviewed in the next section). What has been missing, however, are treatments that reverse the underlying cause of neuropathy symptoms, notably the mitochondrial damage that can lead to nerve problems. Fortunately, some research progress has been made in recent years.
To reverse mitochondrial damage caused by NRTIs in people with peripheral neuropathy, at least two widely available supplements are being studied in clinical trials. The first is acetyl-L-carnitine, believed to improve the function of cellular mitochondria through its ability to transport fatty acids. In a study conducted at the Royal Free and University College Medical School in London and published in 2004, 21 HIV-positive people with NRTI-associated peripheral neuropathy were treated with 1,500mg twice-daily doses of acetyl-L-carnitine for up to 33 months. After six months of treatment, biopsies taken from the patients—and compared to those taken from HIV-negative study volunteers—found significant regrowth in nerves of the skin. Sixteen (76%) patients also reported symptom improvements during the study period.
In another study, reported in 1997, 500 to 1,000mg daily acetyl-L-carnitine reduce neuropathy symptoms in 10 of 16 (63%) HIV-positive patients with peripheral neuropathy. Unfortunately, biopsies were not conducted to measure nerve growth in this study. A third study using a combination of supplements that included acetyl-L-carnitine did not appear to reverse symptoms of peripheral neuropathy or improve neurological tests in HIV-positive people with this side effect.
Uridine, sold as NucleomaxX, is another supplement that may help improve mitochondrial function. Encouraging data using uridine in clinical trials involving people with diabetic neuropathy have been reported. Studies of uridine involving HIV-positive people with neuropathy are being conducted. NucleomaxX is not currently available in the United States.
What about medications to reduce the symptoms of neuropathy?
Non-narcotic pain relievers. These include aspirin, acetaminophen (e.g., Tylenol), ibuprofen (e.g., Advil), and naproxen (e.g., Aleve). All of these are available over-the-counter at pharmacies and grocery stores. These medicines are often quite effective in handling mild pain associated with peripheral neuropathy. While they can irritate the stomach, they are not addictive and can be taken regularly to maintain comfort. Prescription versions of these drugs—which are reimbursed by most private and public health-insurance policies—are available for pain that is slightly more severe.
Topical medications. Lidoderm (5% lidocaine gel), an anesthetic gel applied directly to the skin, is now available with a doctor’s prescription in the United States. However, a clinical trial involving 65 HIV-positive people failed to demonstrate significant reductions in pain caused by peripheral neuropathy.
Qutenza is another product currently being studied to reduce neuropathic pain. The active ingredient in Qutenza, capsaicin, is the substance in hot chili peppers that gives them their spiciness. It was found to work as a pain reliever, and a Qutenza skin patch has been approved to treat the pain associated with a shingles outbreak. Studies in people with HIV who have neuropathy have been promising and are ongoing.
Tricyclic antidepressants. These drugs work by reducing certain chemicals in the brain, called “neurotransmitters,” that are associated with pain and emotional distress. They are often combined with non-narcotic pain relievers (see above) and are usually recommended for the treatment of mild-to-moderate pain. They are also prescribed, in combination with narcotic painkillers, to help manage severe pain. While anecdotal (word-of-mouth) reports from HIV-positive patients and doctors suggest that tricyclic antidepressants are sometimes helpful in managing symptoms of peripheral neuropathy, data from clinical trials are either limited or have not shown that these drugs are, in fact, effective.
The two most common tricyclic antidepressants are Elavil (amitriptyline) and Pamelor (nortriptyline). It is important that low doses of these drugs be used at first, with a slow buildup to the recommended daily doses. Amitriptyline should be started using a dose of 25 mg or less, usually at bedtime. Over time, the dose may be increased to 75 mg a day. With nortriptyline, the recommended starting dose is 10 mg three times a day, building up gradually to 30 mg three times a day. Increasing the dose gradually is necessary to prevent certain side effects, such as dry mouth, problems urinating, and sleepiness, that can occur with both of these drugs. Note: Some protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs) can either increase or decrease blood levels of tricyclic antidepressants. As a result, your doctor may want to regularly check the amount of these drugs in your bloodstream. Be sure to discuss the possibility of drug interactions with your doctor.
Anticonvulsants. Anticonvulsants are normally used to treat epilepsy, another neurological disorder. These drugs help calm the central nervous system, including the part of the nervous system responsible for processing pain. There have been some data from clinical trials, as well as many anecdotal (word-of-mouth) reports from HIV-positive patients and doctors, suggesting that anticonvulsants are sometimes helpful in managing symptoms of peripheral neuropathy.
Lyrica (Pregabalin), Neurontin (gabapentin), Lamictal (lamotrigine), Tegretol (carbamazepine), Dilantin (phenytoin), and Topamax (topiramate) are six anticonvulsants that can be used for pain associated with peripheral neuropathy. As with the tricyclic antidepressants, it might be necessary to increase the doses of these drugs (particularly gabapentin and lamotrigine) over the first few weeks of treatment, and to alter your dose of these drugs if side effects occur. Some of the side effects of anticonvulsants include loss of muscle control, rash, and decreased blood pressure. Note: Some protease inhibitors and non-nucleoside analogues can either increase or decrease blood levels of anticonvulsants. As a result, your doctor may want to regularly check the amount of these drugs in your bloodstream. Be sure to discuss the possibility of drug interactions with your doctor.
Narcotic pain relievers. When the symptoms of peripheral neuropathy get to be too much and don’t subside with the use of the medications discussed above, it might be necessary to use some of the more powerful narcotic drugs to manage the pain. These drugs are usually used in combination with non-narcotic pain relievers, along with tricyclic antidepressants or anticonvulsants. While it’s certainly safe to use narcotic pain relievers to manage pain over the short term—even for HIV-positive people with a history of drug addiction—they can become addictive if used on a long-term basis. Narcotic medications can also cause nausea, vomiting, and sleepiness. Thus, it’s important to work closely with your doctor to find a dose that helps control the pain without the addition of unwanted side effects.
For moderate pain, the recommended narcotic pain relievers include morphine, oxycodone, codeine, and meperidine. For severe pain requiring heavy-duty relief, the options are usually sustained-release morphine, methadone, and fentanyl patches. Low doses of these drugs should be started at first and then gradually increased until the pain is more manageable without additional side effects. Note: Some anti-HIV protease inhibitors and non-nucleoside analogues can either increase or decrease blood levels of narcotic pain relievers. As a result, your doctor may want to regularly check the amount of these drugs in your bloodstream. Be sure to discuss the possibility of drug interactions with your doctor.
Cannabis (marijuana). In February 2007, University of California, San Francisco researchers published data from a placebo-controlled clinical trial evaluating the safety and effectiveness of smoked marijuana for the management of peripheral neuropathy-associated pain. The study volunteers were admitted to UCSF and smoked marijuana (containing 3.56% delta-9 THC, the primary active ingredient in cannabis) or placebo cigarettes three times a day for a total of five days.
Fifty patients completed the entire study. Over the five-day inpatient period, smoking marijuana cigarettes three times a day reduced the pain associated with peripheral neuropathy by 34%, significantly more than the 17% reduction with placebo cigarettes. Half (52%) of those randomized to cannabis experienced at least a 30% reduction in pain, while a quarter (24%) of those randomized to placebo experienced a similar reduction in pain. The first marijuana cigarette reduced chronic pain by an average of 72% vs. 15% with placebo. In terms of safety, no patients withdrew from the study because of adverse events. While side effects were low in both study groups, the severity of side effects were somewhat higher among patients in the cannabis group, notably reports of anxiety, sedation, disorientation, confusion, and dizziness.
Advocacy groups plan to use these data to petition Congress to remove marijuana from Schedule I of the Controlled Substance Act so that it may be consistently prescribed and distributed for medicinal purposes. A number of states have legalized the use of marijuana for medicinal purposes.
What about things I can do for myself to control the pain?
Whether or not you decide to switch your anti-HIV therapies or start taking medications to manage the symptoms of peripheral neuropathy, there are a number of things you can do for yourself to control the pain and discomfort associated with this side effect. Consider some (or all!) of the following:
Avoid ill-fitting shoes. Just as shoes that are too tight can cause throbbing, rubbing, and cramping, shoes that are too loose can actually worsen pain and may not provide enough support for already wobbly feet. The best bet is to wear comfortable, well-fitting sneakers. Sneakers are sturdy enough to provide support, yet flexible enough to provide the feet with the space they need to remain comfortable. If something a bit more dressy is needed, whether it be for work or going out at night, it’s best to invest in a good pair of leather shoes, and to work closely with a knowledgeable salesperson who can work around the specific types of pain you’re dealing with.
Keep your feet and hands cool. Most HIV-positive people with peripheral neuropathy say that the pain is worse during the warm summer months or at night, when the feet are tucked away under sheets and blankets. Let your feet breathe! If at all possible, don’t wear suffocating shoes around the house—opt for a comfortable pair of socks or some soft slippers. Also, don’t cover your feet at night. Cool air in your bedroom can have a numbing effect on your feet. This also helps keep the feet (and hands) free of sheets and blankets, which can sometimes be extremely painful for people with severe peripheral neuropathy.
Treat your feet and hands well. Massaging your hands or feet—or having someone massage them for you—can be extremely relaxing and can increase circulation of the blood to these extremities. Massage can also help spark endorphins (chemicals produced by the body to help control pain). Also try soaking painful hands and feet in cold water.
Last Revised: January 18, 2016