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What is peripheral neuropathy?

Peripheral neuropathy refers to the many conditions that involve damage to the peripheral nervous system, which is a vast communications network that sends signals between the central nervous system (the brain and spinal cord) and all other parts of the body.

Peripheral nerves send many types of sensory information to the central nervous system (CNS), such as the message that your feet are cold. They also carry signals from the CNS to the rest of the body. Best known are the signals to the muscles that tell them to contract, which is how we move, but there are different types of signals that help control everything from our heart and blood vessels, digestion, urination and sexual function to our bones and immune system.

More than 20 million people in the U.S. are estimated to have some form of peripheral neuropathy, but this figure may be significantly higher as not all people with symptoms of neuropathy are tested for the disease and tests currently do not look for all forms of neuropathy.

Nerve signal interruption

The peripheral nerves are like cables that connect different parts of a computer or connect to the Internet. When they malfunction, complex functions can grind to a halt.

Nerve signaling in neuropathy is disrupted in three ways:

Some forms of neuropathy involve damage to only one nerve (mononeuropathy). Neuropathy affecting two or more nerves in different areas is called multiple mononeuropathy or mononeuropathy multiplex. More often, many or most of the nerves are affected (polyneuropathy).

Classifying the nerves and peripheral neuropathies

More than 100 types of peripheral neuropathy have been identified, each with its own symptoms and prognosis. Symptoms vary depending on the type of nervesmotor, sensory, or autonomicthat are damaged.

Most neuropathies affect all three types of nerve fibers to varying degrees; others primarily 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.

About 75 percent of polyneuropathies are length-dependent, meaning the farthest nerve endings in the feet are where the symptoms develop first or are worse. In severe cases, these neuropathies can spread upwards toward the central parts of the body. In non-length dependent polyneuropathies, the symptoms can start around the torso, or are patchy.

Symptoms

Symptoms can range from mild to disabling, 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 advanced care. Unlike nerve cells in the CNS, peripheral nerve cells continue to grow throughout life.

Symptoms are related to the type of nerves affected.

Motor nerve damage is most commonly associated with muscle weakness. Other symptoms include:

Sensory nerve damage causes various symptoms because sensory nerves have a broad range of functions.

Autonomic nerve damage affects the axons in small-fiber neuropathies. Common symptoms include:

Types of peripheral neuropathy

There are several types of peripheral neuropathies, including

Most instances of neuropathy are either acquired, meaning the neuropathy or the inevitability of getting it isn't present from the beginning of life, or genetic. Acquired neuropathies are either symptomatic (the result of another disorder or condition) or idiopathic (meaning it has no known cause).

Acquired peripheral neuropathy causes include:

Genetically caused polyneuropathies are rare. Genetic mutations can either be inherited or arise "de novo," meaning they are completely new to an individual and are not present in either parent. Some genetic mutations 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. The small-fiber neuropathies that present with pain, itch, and autonomic symptoms can be genetic.

Diagnosing peripheral neuropathy

The variability of symptoms that neuropathies can cause often makes diagnosis difficult. A diagnosis of neuropathy can include:

Additional tests may be ordered to help determine the nature and extent of the neuropathy.

Physiologic tests of nerve function

Neuropathology tests of nerve appearance

Autonomic testing

Radiology imaging tests

Muscle and nerve ultrasound is a noninvasive experimental technique for imaging nerves and muscles for injury such as a severed nerve or a compressed nerve. 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 muscle ultrasound.

Treating peripheral neuropathy

Treatments depend entirely on the type of nerve damage, symptoms, and location. Your doctor will explain how nerve damage is causing your specific symptoms and how to minimize and manage them. You may be able to reduce your medication dose or manage your neuropathy without medications. Definitive treatment can allow for functional recovery over time, as long as the nerve cell itself has not died.

Correcting underlying causes can result in the neuropathy resolving on its own as the nerves recover or regenerate. Nerve health and resistance can be improved by healthy lifestyle habits such as maintaining optimal weight, avoiding toxic exposures, eating a balanced diet, and correcting vitamin deficiencies.

Smoking constricts the blood vessels that supply nutrients to the peripheral nerves and can worsen neuropathic symptoms. Exercise can deliver more blood, oxygen, and nutrients to far-off nerve endings, improve muscle strength, and limit muscle atrophy. Self-care skills in people with diabetes and others who have an impaired ability to feel pain can alleviate symptoms and often create conditions that encourage nerve regeneration. Strict control of blood glucose levels can reduce neuropathic symptoms and help people with diabetic neuropathy avoid further nerve damage.

Inflammatory and autoimmune conditions leading to neuropathy can be controlled using immunosuppressive drugs such as prednisone, cyclosporine, or azathioprine. Plasmapheresisa procedure in which blood is removed, cleansed of immune system cells and antibodies, and then returned to the bodycan help reduce inflammation or suppress immune system activity. Agents such as rituximab that target specific inflammatory cells, large intravenously administered doses of immunoglobulins, and antibodies that alter the immune system, also can suppress abnormal immune system activity.

Improving symptoms

Medications recommended for chronic neuropathic pain are also used for other medical conditions. Among the most effective are a class of drugs first marketed to treat depression. Nortriptyline and newer serotonin-norepinephrine reuptake inhibitors such as duloxetine hydrochloride modulate pain by increasing the brain's ability to inhibit incoming pain signals.

Another class of medications that quiets nerve cell electrical signaling is also used for epilepsy. Common drugs include gabapentin, pregabalin, and less often topiramate and lamotrigine. Carbamazepine and oxcarbazepine are particularly effective for trigeminal neuralgia, a focal neuropathy of the face.

Local anesthetics and related drugs that block nerve conduction may help when other medications are ineffective or poorly tolerated. Medications put on the skin (topically administered) are generally appealing because they stay near the skin and have fewer unwanted side effects. Lidocaine patches or creams applied to the skin can be helpful for small painful areas, such as localized chronic pain from mononeuropathies such as shingles. Another topical cream is capsaicin, a substance found in hot peppers that can desensitize peripheral pain nerve endings.Doctor-applied patches that contain higher concentrations of capsaicin offer longer term relief from neuropathic pain and itching, but they worsen small-fiber nerve damage.Weak over-the-counter formulations also are available. Lidocaine or longer acting bupivacaine are sometimes given using implanted pumps that deliver tiny quantities to the fluid that bathes the spinal cord, where they can quiet excess firing of pain cells without affecting the rest of the body. Other drugs treat chronic painful neuropathies by calming excess signaling.

Narcotics (opioids) can be used for pain that doesn't respond to other pain-control medications and if disease-improving treatments aren't fully effective. Because pain relievers that contain opioids can lead to dependence and addiction, their use must be closely monitored by a physician. One of the newest drugs approved for treating diabetic neuropathy is tapentadol, which has both opioid activity and norepinephrine-reuptake inhibition activity of an antidepressant.

Surgery is the recommended treatment for some types of neuropathies. Protruding disks (pinched nerve) in the back or neck that compress nerve roots are commonly treated surgically to free the affected nerve root and allow it to heal. Injuries to a single nerve (mononeuropathy) caused by compression, entrapment, or rarely tumors or infections may require surgery to release the nerve compression. Polyneuropathies that involve more scattered nerve damage, such as diabetic neuropathy, are not helped by surgical intervention. Surgeries or interventional procedures that attempt to reduce pain by cutting or injuring nerves are not often effective as they worsen nerve damage and the parts of the peripheral and central nervous system above the cut often continue to generate pain signals (phantom pain). 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.

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. Although data from controlled clinical trials are not available to broadly establish its efficacy for peripheral neuropathies, in some studies TENS has been shown to improve neuropathic symptoms associated with diabetes.

Prevention

The best treatment is prevention, and strategies for reducing injuries are highly effective and well tested. Since medical procedures ranging from casting fractures to injuries from needles and surgery are another cause, unnecessary procedures should be avoided.

The new adjuvanted vaccine (anadjuvantis an ingredient used in some vaccines that helps create a stronger immune response in people receiving the vaccine)against shingles prevents more than 95 percent of cases and is widely recommended for people over 50, including those who have had previous shingles or vaccination with the older, less effective vaccine.

Diabetes and some other diseases are common preventable causes of neuropathy. People with neuropathy should ask their doctors to minimize use of medications that are known to cause or worsen neuropathy where alternatives exist. Some families with very severe genetic neuropathies use in vitro fertilization (IVF) to prevent transmission to future generations.

The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. NINDS is a component of the National Institutes of Health (NIH), a leading supporter of biomedical research in the world.

NINDS-funded research ranges from clinical studies of the genetics and the natural history of hereditary neuropathies to discoveries of new cause 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. Understanding the causes of neuropathy provides the foundation for finding effective prevention and treatment strategies.

Genetic mutations have been identified in more than 80 distinct hereditary 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. The Inherited Neuropathies Consortium (INC)a group of academic medical centers, patient support organizations, and clinical research resources dedicated to conducting clinical research in Charcot-Marie-Tooth disease and improving the care of people with the diseaseis working to characterize the natural history of several different forms of neuropathy and to identify genes that modify clinical features in these disorders. Knowing which genes are mutated, and what their normal function is, allows precise diagnosis and leads to new therapies that can 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 individuals respond to candidate treatments.

Rapid communication between the peripheral nervous system and the central nervous system often depends on myelination, a process through which special cells called Schwann cells create an insulating coating around axons. Several NINDS-funded studies focus on understanding how myelin protein and membrane production and maintenance in Schwann cells is regulated and how mutations in genes involved in these processes cause peripheral neuropathies. Schwann cells play a critical role in the regeneration of nerve cell axons in the peripheral nervous system. 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-Barr 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 antibodies to cell membrane components cause peripheral nerve damage and how the effects of these antibodies can be blocked. Researchers are also 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 immune-caused, particularly in women and children.

NINDS-supported researchers are also exploring the use of tissue engineered from the cells of humans with peripheral neuropathy as models to identify specific defects in the transport of cellular components 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 this signaling.

For research articles and summaries on peripheral neuropathy, search PubMed, which contains citations from medical journals and other sites.

Learn About Clinical Trials

Clinical trials are studies that allow us to learn more about disorders and improve care. They can help connect patients with new and upcoming treatment options.

Consider participating in a clinical trial so clinicians and scientists can learn more about peripheral neuropathy and other nerve disorders. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of volunteers are neededthose who are healthy or may have an illness or diseaseof 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 database of current and past trials, some of which have research results.

Information and resources on peripheral neuropathy and nerve disease are available from the following organizations:

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