What is peripheral neuropathy?
Peripheral neuropathy refers to the many conditions that involve damage to the peripheral nervous system. The peripheral nervous system is a large communications network that sends signals between the central nervous system (the brain and spinal cord) and all other parts of the body. Peripheral neuropathy affects millions of people in the U.S.
Peripheral nerves send many types of sensory information to the brain, such as the message that your feet are cold. They also carry signals from the brain and spinal cord out to the rest of the body. Peripheral nerves send signals to the muscles that tell them to contract, which is how we move, but also different types of signals help control everything from our heart and blood vessels, digestion, urination, sexual function, and to our bones and immune system.
When peripheral nerves can’t send and receive signals like they should, it can have serious consequences for the body.
In peripheral neuropathy, nerve signaling is disrupted in three ways:
- Signals that should be sent, aren’t
- Signals that are sent when they shouldn’t be
- Errors that change the messages being sent
Some forms of peripheral neuropathy affect only one or a few nerves. Most often, however, many or most of a person’s nerves are affected.
Classes and types of peripheral neuropathy
More than 100 types of peripheral neuropathy have been identified, each with its own symptoms and likely course of progression. Symptoms vary depending on the type of nerves—motor, sensory, or autonomic—that are damaged.
- Motor nerves control the movement of all muscles we consciously control, such as those used for walking, grasping things, or talking
- Sensory nerves transmit information such as the feeling of a light touch, the temperature, or pain from a cut
- Autonomic nerves control muscle and organ function we don’t consciously think about, such as breathing, digesting food, heartbeat, and the function of our glands
Most neuropathies affect all three types of nerve fibers to varying degrees; others mostly affect one or two types. Doctors use terms such as predominantly motor neuropathy, predominantly sensory neuropathy, sensory-motor neuropathy, or autonomic neuropathy to describe different conditions.
Most neuropathies are “length-dependent,” meaning the farthest nerve endings from the brain (those in the feet) are where the symptoms develop first or are worse. In severe cases, these neuropathies can spread upward toward the central parts of the body. In non-length dependent neuropathies, the symptoms can start around the torso, or move around different parts of the body.
Types of peripheral neuropathy
There are several types of peripheral neuropathies.
Inherited peripheral neuropathies include:
- Charcot-Marie-Tooth disease, which affects both sensory and motor nerves (nerves that trigger an impulse for a muscle to contract) in the arms, hands, legs, and feet
- Friedreich ataxia, which causes progressive damage to the nervous system and movement problems
- Giant axonal neuropathy (GAN), which happens when the GAN1 gene is changed and causes the axons, or the message sender of the nerve cell, to become larger than normal and eventually break down, causing movement and sensation problems. GAN is progressive, meaning that it worsens over time. Most children will begin showing signs of GAN before five years of age, and will need to use a wheelchair in the second decade of life. Some children with GAN survive into early adulthood. Currently there is no cure or treatment to stop the progression of this rare disorder.
The following peripheral neuropathies are acquired peripheral neuropathies, meaning the person is not born with them, but develops them during their lifetime. These include:
- Chemotherapy-induced peripheral neuropathy (CIPN), which is a disabling side effect of cancer treatment.
- Guillain-Barré syndrome, which occurs when the body's immune system mistakenly attacks the nerves in the body.
- Diabetic neuropathy, affects people with diabetes. It can affect how you move and process sensations such as hot or cold, and how your body regulates functions like breathing and blood pressure.
- Chronic inflammatory demyelinating polyneuropathy (CIDP), which occurs when the immune system attacks the myelin cover of the nerves (called the myelin sheath). The symptoms of CIDP include progressive weakness and reduced sensations in the arms and legs.
- Meralgia paresthetica, which occurs when a sensory nerve covering the thigh (the lateral femoral cutaneous nerve) is compressed or squeezed. People with the disorder often notice a patch of skin in the area that is sensitive to touch and sometimes painful, numb, or tingling. Most cases improve when the person wears looser clothing or loses weight. Drugs used to treat neurogenic pain, such as antiseizure or antidepressant drugs, may relieve pain. In a few cases, severe pain or pain that won't go away may require surgery. In most cases, the disorder will improve with lifestyle changes or may even go away on its own.
- Multifocal motor neuropathy, which is a rare immune disorder that causes slowly progressive muscle weakness in the hands, with differences from one side of the body to the other in the specific muscles involved. It affects men much more often than women, and the disorder is sometimes mistaken for amyotrophic lateral sclerosis (ALS). But unlike ALS, the disorder can be treated and improvement in muscle strength usually begins within three to six weeks after treatment is started. Some people experience only mild symptoms and do not require treatment. For others, treatment generally includes intravenous immunoglobulin (IVIg), which is a common treatment for peripheral neuropathy caused by autoantibodies, or immunosuppressive therapy with cyclophosphamide. Most who receive treatment early experience little, if any, disability.
Symptoms of peripheral neuropathies
Symptoms of peripheral neuropathy can range from mild to severe but are rarely life-threatening. The symptoms depend on the type of nerve fibers affected and the type and severity of damage. Symptoms may develop over days, weeks, or years. In some cases, symptoms improve on their own and may not require any specific care or treatment. Many types of peripheral neuropathy cause pain. Neuropathic pain is sometimes worse at night, disrupting sleep. It can be caused by pain receptors firing spontaneously without any known trigger, or by problems with signal processing in the spinal cord that may cause severe pain from a light touch that is normally painless. This is called allodynia. For example, a person may experience pain from the touch of their bedsheets.
Symptoms associated with neuropathy in the motor nerves include:
- Muscle weakness
- Painful cramps
- Fasciculations (uncontrolled muscle twitching visible under the skin)
- Muscle shrinking (atrophy)
Symptoms associated with neuropathy in the sensory nerves include:
- Pain and tingling
- Inability to feel vibrations and touch, especially in the hands or feet
- Loss of reflexes
- Loss of position sense, which can leave a person unable to coordinate complex movements like walking, fastening buttons, or maintaining their balance when their eyes are shut
- Inability to feel pain or changes in temperature (due to damage to small fiber nerves)
Symptoms associated with neuropathy in the autonomic nerves include:
- Excess or lack of sweating
- Heat intolerance
- Inability to expand and contract the small blood vessels that regulate blood pressure
- Digestive symptoms
- Rarely, problems eating or swallowing (if the nerves that control the esophagus are affected)
Who is more likely to get peripheral neuropathy?
Peripheral neuropathy is either acquired, meaning it is not something the person is born with, or genetic. Acquired neuropathies can be symptomatic (the result of another disorder or condition) or idiopathic (meaning it has no known cause). Diabetes is the leading cause of peripheral neuropathy in the U.S. About two thirds of people with diabetes have mild to severe nerve problems that can cause numb, tingling, or burning feet, one-sided bands of pain, and numbness and weakness on the trunk or pelvis.
Other possible causes of acquired peripheral neuropathy include:
- Physical injury (trauma), such as from car accidents, falls, sports, and medical procedures. Even less severe traumas can cause serious nerve damage. For example, broken or dislocated bones can exert damaging pressure on neighboring nerves and slipped disks between vertebrae can compress nerve fibers where they emerge from the spinal cord. Arthritis, prolonged pressure on a nerve (such as by a cast) or repetitive, forceful activities can cause ligaments or tendons to swell, which narrows slender nerve pathways.
- Vascular and blood problems that decrease oxygen supply to the peripheral nerves can lead to nerve tissue damage. Diabetes, smoking, and narrowing of the arteries from high blood pressure or atherosclerosis can lead to neuropathy. When the walls of blood vessels thicken and scar due to inflammation, this can impede blood flow and cause nerve damage.
- Autoimmune diseases, in which the immune system mistakenly attacks the body's own tissues, can directly target nerves or cause problems when surrounding tissues compress or entrap nerves.
- Hormonal imbalances can disturb the way the body uses energy (metabolic processes), leading to swollen tissues that can press on peripheral nerves.
- Kidney and liver disorders can lead to high amounts of toxins in the blood that can damage nerve tissue. Most people on dialysis develop forms of peripheral neuropathy.
- Nutritional or vitamin imbalances, alcoholism, and exposure to toxins can damage nerves and cause neuropathy. Vitamin B12 deficiency and excess vitamin B6 are the best-known vitamin-related causes. Some medications have been shown to occasionally cause neuropathy as a side effect, including drugs to treat cancer, HIV/AIDS, heart or blood pressure, infections, autoimmune disease, seizures, and alcohol dependence.
- Certain cancers and tumors cause neuropathy in various ways. Tumors sometimes infiltrate or press on nerve fibers. Paraneoplastic syndromes, a group of rare degenerative disorders that are triggered by the immune system's response to a cancer, can indirectly cause widespread nerve damage.
- Chemotherapy drugs used to treat cancer cause neuropathy in some people. However, not all chemotherapy drugs cause neuropathy and not everyone receiving chemotherapy will develop neuropathy. Chemotherapy-induced peripheral neuropathy may continue long after stopping chemotherapy. Radiation therapy also can cause nerve damage, with symptoms sometimes starting months or years after receiving radiation therapy.
- Infections can attack nerve tissues and cause neuropathy. Viruses such as varicella-zoster virus (which causes chickenpox and shingles), West Nile virus, cytomegalovirus, and herpes simplex target sensory fibers, causing attacks of sharp, lightning-like pain. Lyme disease can cause a range of neuropathic symptoms, often within a few weeks of being infected. HIV can extensively damage the central and peripheral nervous systems. Infections can also trigger autoimmune peripheral neuropathy even though the infection may not necessarily attack the nerve. Zika, COVID, Campylobacter jejuni, Epstein-Barr, and other infectious agents are associated with Guillain-Barré syndrome.
It is rare that the cause of a person’s neuropathy is genetic. Genetic changes that lead to peripheral neuropathy can either be inherited or arise “de novo,” meaning they are unique to an individual and are not present in either parent. Some genetic variants lead to mild neuropathies with symptoms that begin in early adulthood and result in little, if any, significant impairment. More severe hereditary neuropathies often appear in infancy or childhood. While rare, Charcot-Marie-Tooth disease is the most common inherited neurological disorder.
How is peripheral neuropathy diagnosed and treated?
Preventing peripheral neuropathy
In some cases, it may be possible to prevent onset or progression of peripheral neuropathy. For example, to prevent nerve damage related to shingles (such as post-herpetic neuralgia), getting recommended vaccines can be helpful. The shingles vaccine is very effective against shingles and is recommended for almost everyone over age 50. Similarly, for peripheral neuropathies that may be related to exposure to toxins, such as alcohol, minimizing exposure can lower the risk of developing neuropathy.
Diabetes and some other diseases are common preventable causes of neuropathy. Managing diabetes and other conditions, healthy eating, and exercise can also help prevent peripheral neuropathy and reduce symptoms for those who already have it. In some cases, it may be possible for doctors to minimize use of medications that are known to cause or worsen neuropathy if alternatives exist.
Diagnosing peripheral neuropathy
It can be difficult to diagnose peripheral neuropathy given the vide variety of symptoms a person may experience. A doctor may use the following to help diagnose peripheral neuropathy:
- Medical history: A doctor will ask questions about the person’s symptoms and any triggers or relieving factors throughout the day, their work environment, social habits, exposure to toxins, alcohol use, risk of infectious diseases, and family history of neurological diseases.
- Physical and neurological exams: A doctor will look for any evidence of diseases that can cause nerve damage, such as diabetes. A neurological exam includes tests that may help identify the cause of the neuropathic disorder as well as the extent and type of nerve damage. This often includes assessing sensation of touch, vibration, and temperature.
- Body fluid tests: Blood tests can detect diabetes, vitamin deficiencies, liver or kidney dysfunction, other metabolic disorders, infections, and signs of abnormal immune system activity. Less often, cerebrospinal fluids are tested for abnormal proteins or the abnormal immune cell presence.
- Imaging tests: An MRI (magnetic resonance imaging) of the spine can identify pinched nerves, tumors, or other internal problems. Although uncommon, in some cases MRI of an arm or leg may be helpful to identify nerve compression. CT (computed tomography) scans of the back can show herniated disks, spinal stenosis (narrowing of the spinal canal), tumors, and bone and vascular irregularities that may affect a person’s nerves.
- Genetic tests: Genetic tests may be performed to assess for inherited neuropathy.
- EMG (electromyography): EMG evaluates how well nerve and muscles are functioning. This test can include:
- Nerve conduction study (NCS): NCS measures signal strength and speed along specific large motor and sensory nerves. They can help discover nerve damage and identify whether symptoms are caused by degeneration of the axon or the myelin sheath (the insulating layer surrounding the axon).
- Needle exam: Detects abnormal electrical activity in muscle fibers and can help differentiate between muscle and nerve disorders; this test can identify if pinched nerves are present. It involves inserting fine needles into specific muscles to record their electrical activity at rest and during contraction.
- Nerve biopsy: Nerve biopsy involves removing and examining a sample of nerve tissue, usually a sensory nerve from the lower leg (called a sural nerve biopsy). This should be done only when necessary. Although a nerve biopsy can provide the most detailed information about the exact types of nerve cells and cell parts affected, it can further damage the nerve and cause chronic neuropathic pain and sensory loss.
- Neurodiagnostic skin biopsy: Neurodiagnostic skin biopsy allows specialists to examine nerve fiber endings following removal of a tiny piece of skin under local anesthesia. This test is most commonly used to diagnose small fiber neuropathies that don’t respond to standard nerve conduction studies and electromyography.
- Autonomic testing: Several types of autonomic testing can evaluate peripheral neuropathies, one of which is a QSART test that measures the ability to sweat in several sites in the arm and leg. Abnormalities in QSART are associated with small fiber neuropathies.
- Muscle and nerve ultrasound: Muscle and nerve ultrasound is a noninvasive experimental technique for finding severed or compressed nerves. Ultrasound imaging of the muscles can detect abnormalities that may be related to a muscle or nerve disorder. Certain inherited muscle disorders have characteristic patterns on a muscle ultrasound.
Treating peripheral neuropathy
Treatment for peripheral neuropathy depends on the type and location of nerve damage and the person’s symptoms. A doctor can explain how nerve damage is causing the person’s specific symptoms and how to minimize and manage them. Sometimes, when the underlying cause of the neuropathy is corrected, it can resolve on its own as nerves recover and regrow.
Lifestyle changes like quitting smoking, avoiding toxins (like alcohol and drugs), exercising, eating healthfully, and maintaining a healthy weight can all support healthier nerves. Managing diabetes and keeping blood glucose at safe levels may help reduce or eliminate the symptoms of diabetic neuropathy.
Intravenous immunoglobulin (IVIg) is a common treatment for peripheral neuropathy caused by autoantibodies. IVIg contains immunoglobulins. Some people whose neuropathy symptoms are caused by inflammation or autoimmune conditions may see improvements in their condition using steroids and immunosuppressive drugs such as prednisone, cyclosporine, or azathioprine. Plasmapheresis—a procedure in which blood is removed, cleansed of immune system cells and antibodies, and then returned to the body—can help reduce inflammation and cut down on immune system activity, as can immunoglobulin, and inflammatory medications such as rituximab.
Many people with neuropathy can manage their symptoms without medication. Over time, as the nerves heal, many people can reduce the dose of their medications or stop taking them altogether. Talk with a doctor before stopping taking any medication.
For people whose motor nerves are affected, hand or foot braces can help reduce physical disability and pain associated with peripheral neuropathy, and orthopedic shoes can improve walking problems and help prevent foot injuries. People with carpal tunnel problems can use splints to help position the wrist to reduce pressure on the compressed nerve and allow it to heal. Some people with severe weakness benefit from surgery to relieve pressure on a nerve.
When autonomic nerves are affected by peripheral neuropathy, it is important to manage these symptoms with a medical professional. For example, people with orthostatic hypotension can take medications to stabilize blood pressure and get in the habit of standing up slowly.
Treating and managing neuropathic pain
Neuropathic pain, itching, and other sensory symptoms can be difficult to control without medication. People with chronic neuropathic pain may be prescribed medications more commonly used to treat depression (including serotonin-norepinephrine reuptake inhibitors), or epilepsy. Common medications include duloxetine hydrochloride, nortriptyline, gabapentin, pregabalin, and less often topiramate and lamotrigine.
Local anesthetics and related drugs that block nerve conduction may help when other medications don’t work or cause unwanted side effects. These include lidocaine patches or a topic cream called capsaicin, which can be helpful for small painful areas. Other drugs treat chronic painful neuropathies by calming excess signaling. Narcotics (opioids) are not recommended for treatment of pain related to peripheral neuropathy.
Behavioral strategies, including meditation and talk therapy, can help some people to cope with chronic pain as well as depression and anxiety that many may feel following nerve injury. Complementary treatments such as acupuncture, massage, and tai chi, may help people manage chronic neuropathic pain. Transcutaneous electrical nerve stimulation (TENS) is a noninvasive intervention used for pain relief in a range of conditions. TENS involves attaching electrodes to the skin at the site of pain or near associated nerves and then administering a gentle electrical current. TENS may be prescribed in combination with other treatments for severe forms of nerve pain.
Most neuropathies involve scattered nerve damage and are not helped by surgery. Surgeries or other procedures that attempt to reduce pain by cutting or injuring nerves are not often effective as they worsen nerve damage and can lead to “phantom pain”. The only neuropathy treated with surgery is carpal tunnel syndrome. More sophisticated and less damaging procedures such as electrically stimulating remaining peripheral nerve fibers or pain-processing areas of the spinal cord or brain have largely replaced these surgeries.
What are the latest updates on peripheral neuropathy?
NINDS, a part of the National Institutes of Health (NIH), is the nation’s leading federal funder of research on neurological disorders. NINDS-funded research ranges from clinical studies of the genetics and the natural history of hereditary neuropathies to discoveries of new causes and treatments for neuropathy, to basic science investigations of the biological mechanisms responsible for chronic neuropathic pain. Together, these diverse research areas will advance the development of new therapeutic and preventive strategies for peripheral neuropathies.
NINDS supports studies to understand the disease mechanisms of these conditions and to identify other genetic defects that may play roles in causing or modifying the course of disease. Genetic mutations have been identified in more than 80 distinct hereditary neuropathies. NINDS also supports the NIH Rare Diseases Clinical Research Network, which is made up of different research consortia aimed at improving the availability of rare diseases information, clinical studies, and clinical research information. NINDS has supported the network's Inherited Neuropathies Consortium (INC), which is working to characterize the natural history of several different forms of neuropathy, identify genes that modify a person’s symptoms, and develop therapies to prevent or reduce nerve damage. INC is also developing and testing biomarkers (signs that can indicate the diagnosis or progression of a disease) and clinical outcome measures that will be needed in future clinical trials to determine whether people in the trials are responding to treatments being tested.
Rapid communication between the peripheral nervous system and the central nervous system depends on myelination, a process through which special cells called Schwann cells create an insulating coating around axons (called myelin). Schwann cells play a critical role in the regeneration of nerve cell axons in the peripheral nervous system. Several NINDS-funded studies focus on understanding how myelin production (specific proteins and membrane organization) and maintenance in Schwann cells is regulated and how mutations in genes involved in these processes cause peripheral neuropathies. By better understanding myelination and Schwann cell function, researchers hope to find targets for new therapies to treat or prevent nerve damage associated with neuropathy.
In inflammatory peripheral neuropathies such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP), the body's immune system mistakenly attacks peripheral nerves, damaging myelin and weakening signaling along affected nerves. NINDS-supported researchers hope to better understand how auto-antibodies cause peripheral nerve damage and how the effects of these antibodies can be blocked. Researchers are studying how mutations in the Autoimmune Regulator (AIRE) gene in a mouse model of CIDP cause the immune system to attack peripheral nerves. NINDS research has helped discover that some types of small-fiber polyneuropathy appear to be caused by problems in the person’s immune response, particularly in women and children.
NINDS-supported researchers are also exploring the use of tissue engineered from donated cells from people with peripheral neuropathy as models to identify specific problems in how cellular components travel along axons and the interactions of nerves with muscles. Such tissue engineering approaches may eventually lead to new therapeutics for peripheral neuropathies.
In addition to efforts to treat or prevent underlying nerve damage, other NINDS-supported studies are informing new strategies for relieving neuropathic pain, fatigue, and other neuropathy symptoms. Researchers are investigating the pathways that carry pain signals to the brain and are working to identify substances that will block these signals before they cause pain.
NIH-supported researchers have identified a pathway common to several types of axonal peripheral neuropathies (APNs), including several forms of Charcot-Marie-Tooth disease, and have identified a possible drug target that could help treat the disease. Previous genetic studies have shown that some APNs are caused by mutations that prevent cells’ ability to make proteins. This causes stress within the motor neurons affected by APNs, particularly through a mechanism called the integrated stress response (ISR), ultimately leading to degeneration of nerve structures. One of the proteins previously shown in the activation of the ISR, GCN2, has also been connected to defects in protein translation. Using a mouse model, the researchers studied APN mice that were also missing GCN2. These mice began to develop symptoms of the disease around two weeks of age, but the disease did not progress much beyond the initial stages. When the APN mice were treated with a drug to stop GCN2 from working, they showed improvements in many symptoms. While still in its early stages, this research may lead to future therapeutics to slow progression of peripheral neuropathy by blocking GCN2.
More information about peripheral neuropathy research can be found using NIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and resources from these projects. For research articles and summaries on peripheral neuropathy, search PubMed, which contains citations from medical journals and other sites.
How can I or my loved one help improve care for people with peripheral neuropathy?
Consider participating in a clinical trial so clinicians and scientists can learn more about peripheral neuropathy and other nerve disorders. Clinical research with human participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.
All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.
For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with peripheral neuropathy at Clinicaltrials.gov, a searchable database of current and past clinical trials and research results.
Where can I find more information about peripheral neuropathy?