Pain arthritis neuropathy



by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit




Pain is ubiquitous in a rheumatology practice.

It is a symptom of many medical disorders. Two of the most common disease categories where pain is a prominent feature are arthritis and neuropathy (the pain that is due to nerve irritation or damage).

This page discusses both these conditions with information obtained from the National Institutes of Health.

Rheumatic diseases – arthritis- are characterized by inflammation (signs are redness and/or heat, swelling, and pain) and loss of function of one or more connecting or supporting structures of the body. They especially affect joints, tendons, ligaments, bones, and muscles. Common symptoms are pain, swelling, and stiffness. Some rheumatic diseases can also involve internal organs. There are more than 100 rheumatic diseases.

Many people use the word "arthritis" to refer to all rheumatic diseases. However, the word literally means joint inflammation. The many different kinds of arthritis comprise just a portion of the rheumatic diseases. Some rheumatic diseases are described as connective tissue diseases because they affect the supporting framework of the body and its internal organs. Others are known as autoimmune diseases because they occur when the immune system, which normally protects the body from infection and disease, harms the body's own healthy tissues. Throughout this fact sheet the terms "arthritis" and "rheumatic diseases" are sometimes used interchangeably.



Examples of Rheumatic Diseases

• Osteoarthritis--This is the most common type of arthritis, affecting an estimated 30 million adults in the United States. Osteoarthritis primarily affects cartilage, which is the tissue that cushions the ends of bones within the joint. In osteoarthritis, the cartilage begins to fray and may entirely wear away. Osteoarthritis can cause joint pain and stiffness. Disability results most often when the disease affects the spine and the weight-bearing joints (the knees and hips).
• Rheumatoid arthritis--This inflammatory disease of the synovium, or lining of the joint, results in pain, stiffness, swelling, joint damage, and loss of function of the joints. Inflammation most often affects joints of the hands and feet and tends to be symmetrical (occurring equally on both sides of the body). This symmetry helps distinguish rheumatoid arthritis from other forms of the disease. About 1 percent of the U.S. population (about 2.1 million people) has rheumatoid arthritis.
• Juvenile rheumatoid arthritis--This is the most common form of arthritis in childhood, causing pain, stiffness, swelling, and loss of function of the joints. The arthritis may be associated with rashes or fevers, and may affect various parts of the body.
• Fibromyalgia--Fibromyalgia is a chronic disorder that causes pain throughout the tissues that support and move the bones and joints. Pain, stiffness, and localized tender points occur in the muscles and tendons, particularly those of the neck, spine, shoulders, and hips. Patients may also experience fatigue and sleep disturbances.
• Systemic lupus erythematosus--Systemic lupus erythematosus (also known as lupus or SLE) is an autoimmune disease in which the immune system harms the body's own healthy cells and tissues. This can result in inflammation of and damage to the joints, skin, kidneys, heart, lungs, blood vessels, and brain.
• Scleroderma--Also known as systemic sclerosis, scleroderma means literally "hard skin." The disease affects the skin, blood vessels, and joints. It may also affect internal organs, such as the lungs and kidneys. In scleroderma, there is an abnormal and excessive production of collagen (a fiber-like protein) in the skin or internal organs.
• Spondyloarthropathies--This group of rheumatic diseases principally affects the spine. One common form--ankylosing spondylitis--not only affects the spine, but may also affect the hips, shoulders, and knees as the tendons and ligaments around the bones and joints become inflamed, resulting in pain and stiffness. Ankylosing spondylitis tends to affect people in late adolescence or early adulthood. Reactive arthritis, sometimes called Reiter's syndrome, is another spondyloarthropathy. It develops after an infection involving the lower urinary tract, bowel, or other organ and is commonly associated with eye problems, skin rashes, and mouth sores.
• Gout--This type of arthritis results from deposits of needle-like crystals of uric acid in the joints. The crystals cause inflammation, swelling, and pain in the affected joint, which is often the big toe.
• Infectious arthritis--This is a general term used to describe forms of arthritis that are caused by infectious agents, such as bacteria or viruses. Parvovirus arthritis and gonococcal arthritis are examples of infectious arthritis. Arthritis symptoms may also occur in Lyme disease, which is caused by a bacterial infection following the bite of certain ticks. In those cases of arthritis caused by bacteria, early diagnosis and treatment with antibiotics are crucial to get rid of the infection and minimize damage to the joints.
• Polymyalgia rheumatica--Because this disease involves tendons, muscles, ligaments, and tissues around the joint, symptoms often include pain, aching, and morning stiffness in the shoulders, hips, neck, and lower back. It is sometimes the first sign of giant cell arteritis, a disease of the arteries characterized by inflammation, weakness, weight loss, and fever.
• Polymyositis--This is a rheumatic disease that causes inflammation and weakness in the muscles. The disease may affect the whole body and cause disability.
• Psoriatic arthritis--This form of arthritis occurs in some patients with psoriasis, a scaling skin disorder. Psoriatic arthritis often affects the joints at the ends of the fingers and toes and is accompanied by changes in the fingernails and toenails. Back pain may occur if the spine is involved.
• Bursitis--This condition involves inflammation of the bursae, small, fluid-filled sacs that help reduce friction between bones and other moving structures in the joints. The inflammation may result from arthritis in the joint or injury or infection of the bursae. Bursitis produces pain and tenderness and may limit the movement of nearby joints.
• Tendinitis (Tendonitis)--This condition refers to inflammation of tendons (tough cords of tissue that connect muscle to bone) caused by overuse, injury, or a rheumatic condition. Tendinitis produces pain and tenderness and may restrict movement of nearby joints.


What Causes Rheumatic Disease?

Scientists are studying risk factors that increase the likelihood of developing a rheumatic disease. Some of these factors have been identified. For example, in osteoarthritis, inherited cartilage weakness or excessive stress on the joint from repeated injury may play a role. In lupus, rheumatoid arthritis, and scleroderma, the combination of genetic factors that determine susceptibility and environmental triggers are believed to be important. Family history also plays a role in some diseases such as gout and ankylosing spondylitis.

Gender is another factor in some rheumatic diseases. Lupus, rheumatoid arthritis, scleroderma, and fibromyalgia are more common among women. (See next section for details.) This indicates that hormones or other male-female differences may play a role in the development of these conditions.



Who Is Affected by Arthritis and Rheumatic Conditions?

An estimated 43 million people in the United States have arthritis or other rheumatic conditions. By the year 2020, this number is expected to reach 60 million. Rheumatic diseases are the leading cause of disability among adults age 65 and older.

Rheumatic diseases affect people of all races and ages. Some rheumatic conditions are more common among certain populations. For example:

• Rheumatoid arthritis occurs two to three times more often in women than in men.
• Scleroderma is more common in women than in men.
• Nine out of 10 people who have lupus are women.
• Nine out of 10 people who have fibromyalgia are women.
• Gout is more common in men than in women.
• Lupus is three times more common in African American women than in Caucasian women.
• Ankylosing spondylitis is more common in men than in women.


What Are the Symptoms of Arthritis?

Different types of arthritis have different symptoms. In general, people who have arthritis feel pain and stiffness in the joints. Some of the more common symptoms are listed in the box. Early diagnosis and treatment help decrease further joint damage and help control symptoms of arthritis and many other rheumatic diseases.



Common Symptoms of Arthritis

• Swelling in one or more joints
• Stiffness around the joints that lasts for at least 1 hour in the early morning
• Constant or recurring pain or tenderness in a joint
• Difficulty using or moving a joint normally
• Warmth and redness in a joint




How Are Rheumatic Diseases Diagnosed?

Diagnosing rheumatic diseases can be difficult because some symptoms and signs are common to many different diseases. A general practitioner or family doctor may be able to evaluate a patient or refer him or her to a rheumatologist (a doctor who specializes in treating arthritis and other rheumatic diseases).

The doctor will review the patient's medical history, conduct a physical examination, and obtain laboratory tests and x rays or other imaging tests. The doctor may need to see the patient more than once to make an accurate diagnosis.



It is vital for people with joint pain to give the doctor a complete medical history. Answers to the following questions will help the doctor make an accurate diagnosis:

• Is the pain in one or more joints?
• When does the pain occur?
• How long does the pain last?
• When did you first notice the pain?
• What were you doing when you first noticed the pain?
• Does activity make the pain better or worse?
• Have you had any illnesses or accidents that may account for the pain?
• Is there a family history of any arthritis or other rheumatic disease?
• What medicine(s) are you taking?


Because rheumatic diseases are so diverse and sometimes involve several parts of the body, the doctor may ask many other questions.

It may be helpful for people to keep a daily journal that describes the pain. Patients should write down what the affected joint looks like, how it feels, how long the pain lasts, and what they were doing when the pain started.



The doctor will examine the patient's joints for redness, warmth, damage, ease of movement, and tenderness. Because some forms of arthritis, such as lupus, may affect other organs, a complete physical examination that includes the heart, lungs, abdomen, nervous system, eyes, ears, and throat may be necessary. The doctor may order some laboratory tests to help confirm a diagnosis. Samples of blood, urine, or synovial fluid (lubricating fluid found in the joint) may be needed for the tests.

Common laboratory tests and procedures include the following:

Antinuclear antibody (ANA)--This test checks blood levels of antibodies that are often present in people who have connective tissue diseases or other autoimmune disorders, such as lupus. Since the antibodies react with material in the cell's nucleus (control center), they are referred to as antinuclear antibodies. There are also tests for individual types of ANAs that may be more specific to people with certain autoimmune disorders. ANAs are also sometimes found in people who do not have an autoimmune disorder. Therefore, having ANAs in the blood does not necessarily mean that a person has a disease.
C-reactive protein test--This is a nonspecific test used to detect generalized inflammation. Levels of the protein are often increased in patients with active disease such as rheumatoid arthritis, and may decline when corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammation.
Complement--This test measures the level of complement, a group of proteins in the blood. Complement helps destroy foreign substances, such as germs, that enter the body. A low blood level of complement is common in people who have active lupus.
Complete blood count (CBC)--This test determines the number of white blood cells, red blood cells, and platelets present in a sample of blood. Some rheumatic conditions or drugs used to treat arthritis are associated with a low white blood count (leukopenia), low red blood count (anemia), or low platelet count (thrombocytopenia). When doctors prescribe medications that affect the CBC, they periodically test the patient's blood.
Creatinine--This blood test is commonly ordered in patients who have a rheumatic disease, such as lupus, to monitor for underlying kidney disease. Creatinine is a breakdown product of creatine, which is an important component of muscle. It is excreted from the body entirely by the kidneys, and the level remains constant and normal when kidney function is normal.
Erythrocyte sedimentation rate (sed rate)--This blood test is used to detect inflammation in the body. Higher sed rates indicate the presence of inflammation and are typical of many forms of arthritis, such as rheumatoid arthritis and ankylosing spondylitis, and many of the connective tissue diseases.
Hematocrit (PCV, packed cell volume)--This test and the test for hemoglobin (a substance in the red blood cells that carries oxygen throughout the body) measure the number of red blood cells present in a sample of blood. A decrease in the number of red blood cells (anemia) is common in people who have inflammatory arthritis or another rheumatic disease.
Rheumatoid factor--This test detects the presence of rheumatoid factor, an antibody found in the blood of most (but not all) people who have rheumatoid arthritis. Rheumatoid factor may be found in many diseases besides rheumatoid arthritis, and sometimes in people without health problems.
Synovial fluid examination--Synovial fluid may be examined for white blood cells (found in patients with rheumatoid arthritis and infections), bacteria or viruses (found in patients with infectious arthritis), or crystals in the joint (found in patients with gout or other types of crystal-induced arthritis). To obtain a specimen, the doctor injects a local anesthetic, then inserts a needle into the joint to withdraw the synovial fluid into a syringe. The procedure is called arthrocentesis or joint aspiration.
Urinalysis--In this test, a urine sample is studied for protein, red blood cells, white blood cells, and bacteria. These abnormalities may indicate kidney disease, which may be seen in several rheumatic diseases, including lupus. Some medications used to treat arthritis can also cause abnormal findings on urinalysis.
White blood cell count (WBC)--This test determines the number of white blood cells present in a sample of blood. The number may increase as a result of infection or decrease in response to certain medications or in certain diseases, such as lupus. Low numbers of white blood cells increase a person's risk of infections.


X Rays and Other Imaging Procedures

To see what the joint looks like inside, the doctor may order x rays or other imaging procedures. X rays provide an image of the bones, but they do not show cartilage, muscles, and ligaments. Other noninvasive imaging methods such as computed tomography (CT or CAT scan), and magnetic resonance imaging (MRI) show the whole joint.

Treatments for rheumatic diseases include rest and relaxation, exercise, proper diet, medication, and instruction about the proper use of joints and ways to conserve energy. Other treatments include the use of pain relief methods and assistive devices, such as splints or braces. In severe cases, surgery may be necessary. The doctor and the patient work together to develop a treatment plan that helps the patient maintain or improve his or her lifestyle. Treatment plans usually combine several types of treatment and vary depending on the rheumatic condition and the patient.

People who have a rheumatic disease should develop a comfortable balance between rest and activity. One sign of many rheumatic conditions is fatigue. Patients must pay attention to signals from their bodies. For example, when experiencing pain or fatigue, it is important to take a break and rest. Too much rest, however, may cause muscles and joints to become stiff.

People with a rheumatic disease such as arthritis can participate in a variety of sports and exercise programs. Physical exercise can reduce joint pain and stiffness and increase flexibility, muscle strength, and endurance. It also helps with weight reduction and contributes to an improved sense of well-being. Before starting any exercise program, people with arthritis should talk with their doctor. Exercises that doctors often recommend include:

• Range-of-motion exercises (e.g., stretching, dance) to help maintain normal joint movement, maintain or increase flexibility, and relieve stiffness.
• Strengthening exercises (e.g., weight lifting) to maintain or increase muscle strength. Strong muscles help support and protect joints affected by arthritis.
• Aerobic or endurance exercises (e.g., walking, bicycle riding) to improve cardiovascular fitness, help control weight, and improve overall well-being. Studies show that aerobic exercise can also reduce inflammation in some joints.


Another important part of a treatment program is a well-balanced diet. Along with exercise, a well-balanced diet helps people manage their body weight and stay healthy. Weight control is important to people who have arthritis because extra weight puts extra pressure on some joints and can aggravate many types of arthritis. Diet is especially important for people who have gout. People with gout should avoid alcohol and foods that are high in purines, such as organ meats (liver, kidney), sardines, anchovies, and gravy.

A variety of medications are used to treat rheumatic diseases. The type of medication depends on the rheumatic disease and on the individual patient. The medications used to treat most rheumatic diseases do not provide a cure, but rather limit the symptoms of the disease. Infectious arthritis and gout are exceptions if medications are used properly. Another example is Lyme disease, caused by the bite of certain ticks, where symptoms of arthritis may be prevented or may disappear if the infection is caught early and treated with antibiotics.

Medications commonly used to treat rheumatic diseases provide relief from pain and inflammation. In some cases, the medication may slow the course of the disease and prevent further damage to joints or other parts of the body.

The doctor may delay using medications until a definite diagnosis is made because medications can hide important symptoms (such as fever and swelling) and thereby interfere with diagnosis. Patients taking any medication, either prescription or over-the-counter, should always follow the doctor's instructions. The doctor should be notified immediately if the medicine is making the symptoms worse or causing other problems, such as an upset stomach, nausea, or headache. The doctor may be able to change the dosage or medicine to reduce these side effects.

Analgesics (pain relievers) such as acetaminophen (Tylenol)* and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are used to reduce the pain caused by many rheumatic conditions. NSAIDs have the added benefit of decreasing the inflammation associated with arthritis. A common side effect of NSAIDs is stomach irritation, which can often be reduced by changing the dosage or medication. Newer NSAIDs, including celecoxib (Celebrex), were introduced to reduce gastrointestinal side effects and offer additional options for treatment. However, even new medications are occasionally associated with reactions ranging from mild to severe, and their long-term effects are still being studied. All NSAIDS are associated with an increased risk of heart attack or stroke.

Topical NSIADS such as Pennsaid and Voltaren gel may be safer.

Depending on the type of arthritis, a person may be asked to take a disease-modifying antirheumatic drug (DMARD). This category includes several unrelated medications that are intended to slow or prevent damage to the joint and thereby prevent disability and discomfort. DMARDs include methotrexate, sulfasalazine, and leflunomide (Arava).

Biological response modifiers are new drugs used for the treatment of rheumatoid arthritis. They can help reduce inflammation and structural damage of the joints by blocking the reaction of a substance called tumor necrosis factor, a protein involved in immune system response. These drugs include Enbrel, Remicade, Humira, Cimzia, and Simponi.

Other biologics with different modes of action have also been developed. These include Actemra, Orencia, Rituxan, and Xeljanz.

Corticosteroids, such as prednisone, cortisone, solumedrol, and hydrocortisone, are used to treat many rheumatic conditions because they decrease inflammation and suppress the immune system. The dosage of these medications will vary depending on the diagnosis and the patient. Again, the patient and doctor must work together to determine the right amount of medication. Corticosteroids can be given by mouth, in creams applied to the skin, or by injection. Short-term side effects of corticosteroids include swelling, increased appetite, weight gain, and emotional ups and downs. These side effects generally stop when the drug is stopped. It can be dangerous to stop taking corticosteroids suddenly, so it is very important that the doctor and patient work together when changing the corticosteroid dose. Side effects that may occur after long-term use of corticosteroids include stretch marks, excessive hair growth, osteoporosis, high blood pressure, damage to the arteries, high blood sugar, infections, and cataracts.

Hyaluronic acid products like Hyalgan and Synvisc mimic a naturally occurring body substance that lubricates the knee joint. They are usually injected directly into the joint to help provide temporary relief of pain and flexible joint movement.

Transcutaneous electrical nerve stimulation (TENS) has been found effective in modifying pain perception. TENS blocks pain messages to the brain with a small device that directs mild electric pulses to nerve endings that lie beneath the painful area of the skin.

Heat and cold can both be used to reduce the pain and inflammation of arthritis. The patient and doctor can determine which one works best.

Heat therapy increases blood flow, tolerance for pain, and flexibility. Heat therapy can involve treatment with paraffin wax, microwaves, ultrasound, or moist heat. Physical therapists are needed for some of these therapies, such as microwave or ultrasound therapy, but patients can apply moist heat themselves. Some ways to apply moist heat include placing warm towels or hot packs on the inflamed joint or taking a warm bath or shower.

Cold therapy numbs the nerves around the joint (which reduces pain) and may relieve inflammation and muscle spasms. Cold therapy can involve cold packs, ice massage, soaking in cold water, or over-the-counter sprays and ointments that cool the skin and joints.

Capsaicin cream is a preparation put on the skin to relieve joint or muscle pain when only one or two joints are involved.

Hydrotherapy involves exercising or relaxing in warm water. The water takes some weight off painful joints, making it easier to exercise. It helps relax tense muscles and relieve pain.

Mobilization therapies include traction (gentle, steady pulling), massage, and manipulation. (Someone other than the patient moves stiff joints through their normal range of motion.) When done by a trained professional, these methods can help control pain, increase joint motion, and improve muscle and tendon flexibility.

Relaxation therapy helps reduce pain by teaching people various ways to release muscle tension throughout the body. In one method of relaxation therapy, known as progressive relaxation, the patient tightens a muscle group and then slowly releases the tension. Doctors and physical therapists can teach patients a variety of relaxation techniques.

The most common assistive devices for treating arthritis pain are splints and braces, which are used to support weakened joints or allow them to rest. Some of these devices prevent the joint from moving; others allow some movement. A splint or brace should be used only when recommended by a doctor or therapist, who will show the patient the correct way to put the device on, ensure that it fits properly, and explain when and for how long it should be worn. The incorrect use of a splint or brace can cause joint damage, stiffness, and pain.

A person with arthritis can use other kinds of devices to ease the pain. For example, the use of a cane when walking can reduce some of the weight placed on a knee or hip affected by arthritis. A shoe insert (orthotic) can ease the pain of walking caused by arthritis of the foot or knee. Other devices can help with activities such as opening jars, closing zippers, and holding pencils.

Surgery may be required to repair damage to a joint after injury or to restore function or relieve pain in a joint damaged by arthritis. The doctor may recommend arthroscopic surgery, bone fusion (surgery in which bones in the joint are fused or joined together), or arthroplasty (also known as total joint replacement, in which the damaged joint is removed and replaced with an artificial one).

Nutritional supplements are often reported as helpful in treating rheumatic diseases. These include products such as S-adenosylmethionine (SAM-e) for osteoarthritis and fibromyalgia, dehydroepiandrosterone (DHEA) for lupus, and glucosamine and chondroitin sulfate for osteoarthritis. Reports on the safety and effectiveness of these products should be viewed with caution since very few claims have been carefully evaluated.

At this time, the only type of arthritis that can be cured is that caused by infections. Although symptoms of other types of arthritis can be effectively managed with rest, exercise, and medication, there are no cures. Some people claim to have been cured by treatment with herbs, oils, chemicals, special diets, radiation, or other products. However, there is no scientific evidence that such treatments cure arthritis. Moreover, some may lead to serious side effects. Patients should talk to their doctor before using any therapy that has not been prescribed or recommended by the health care team caring for the patient.

The role you play in planning your treatment is very important. It is vital for you to have a good relationship with your doctor in order to work together. You should not be afraid to ask questions about your condition or treatment. You must understand the treatment plan and tell the doctor whether or not it is helping you. Research has shown that patients who are well informed and participate actively in their own care experience less pain and make fewer visits to the doctor.

Studies show that an estimated 18 percent of Americans who have arthritis or other rheumatic conditions believe that their condition limits their activities. People with arthritis may find that they can no longer participate in some of their favorite activities, which can affect their overall well-being. Even when arthritis impairs only one joint, a person may have to change many daily activities to protect that joint from further damage and reduce pain. When arthritis affects the entire body, as it does in people with rheumatoid arthritis or fibromyalgia, many daily activities have to be changed to deal with pain, fatigue, and other symptoms.

Changes in the home may help a person with chronic arthritis continue to live safely, productively, and with less pain. People with arthritis may become weak, lose their balance, or fall. In the bathroom, installing grab bars in the tub or shower and by the toilet, placing a secure seat in the tub, and raising the height of the toilet seat can help. Special kitchen utensils can accommodate hands affected by arthritis to make meal preparation easier. An occupational therapist can help people who have rheumatic conditions identify and make adjustments in their homes to create a safer, more comfortable, and more efficient environment.

Friends and family members can help a patient with a rheumatic condition by learning about that condition and understanding how it affects the patient's life. Friends and family can provide emotional and physical assistance. Their support, as well as support from other people who have the same disease, can make it easier to cope. The Arthritis Foundation has a wealth of information to help people with arthritis.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH), leads the Federal medical research effort in arthritis and rheumatic diseases. The NIAMS sponsors research and research training on the NIH campus in Bethesda, Maryland, and at universities and medical centers throughout the United States. Research activities include both basic (laboratory) and clinical (involving patients) research studies to better understand what causes these conditions and how best to treat and prevent them.

The NIAMS currently supports three types of research centers that study arthritis, rheumatic diseases, and other musculoskeletal conditions: Multidisciplinary Clinical Research Centers (MCRCs), Specialized Centers of Research (SCORs), and Core Centers. A list of these centers and their locations can be obtained from the Institute (listed at the end of this fact sheet).

The MCRCs are programs that focus on clinical research designed to assess and improve outcomes for patients affected by arthritis and other rheumatic diseases, musculoskeletal disorders (including bone and muscle diseases), and skin diseases. Each center studies one or more of the diseases within the NIAMS mission and provides resources for developing clinical projects using more than one approach.

Each SCOR focuses on a single disease. Currently, rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, osteoporosis, and scleroderma are being studied. Combining laboratory and clinical studies under one roof speeds up research on the causes of these diseases and hastens transfer of advances from the laboratory to the bedside to improve patient care.

Core Centers promote interdisciplinary collaborative efforts among scientists doing high-quality research related to a common theme. By providing funding for facilities, pilot and feasibility studies, and program enrichment activities at the Core Center, the Institute reinforces investigations already underway in NIAMS program areas. Current centers include Rheumatic Diseases Research Core Centers, Skin Disease Research Core Centers, and Core Centers for Musculoskeletal Disorders.

Research registries provide a means for collecting clinical, demographic, and laboratory information from patients and, sometimes, their relatives. These registries facilitate studies that could ultimately lead to improved diagnosis, treatment, and prevention. NIAMS currently supports research registries for rheumatoid arthritis, antiphospholipid syndrome (an autoimmune disorder), ankylosing spondylitis, lupus and neonatal lupus, scleroderma, juvenile rheumatoid arthritis, and juvenile dermatomyositis.

Some current NIAMS research efforts in rheumatic diseases are outlined below. Recent scientific breakthroughs in basic research have provided new information about what happens to the body's cells and other structures as rheumatic diseases progress. Biomarkers (laboratory and imaging signposts that detect disease) help researchers determine the likelihood that a person will develop a specific disease and its possible severity and outcome. Biomarkers have the potential to lead to novel and more effective ways to predict and monitor disease activity and responses to treatment. The NIAMS supports research on biomarkers for rheumatic and skin diseases, including a new initiative on osteoarthritis. Additional studies on specific rheumatic diseases follow.



Rheumatoid Arthritis

Researchers are trying to identify the cause of rheumatoid arthritis in order to develop better and more specific treatments. They are examining the role that the endocrine (hormonal), nervous, and immune systems play, and the ways in which these systems interact with environmental and genetic factors in the development of rheumatoid arthritis. Some scientists are trying to determine whether an infectious agent triggers rheumatoid arthritis. Others are studying the role of certain enzymes (specialized proteins in the body that spark biochemical reactions) in breaking down cartilage. Researchers are also trying to identify the genetic factors that place some people at higher risk than others for developing rheumatoid arthritis.

Moreover, scientists are looking at new ways to treat rheumatoid arthritis. They are experimenting with new drugs and "biologic agents" that selectively block certain immune system activities associated with inflammation.

Novel studies using imaging technologies are underway as well. These techniques help identify targets for new drugs by allowing researchers to see changes in cells during the disease process.



Osteoarthritis

The NIAMS has embarked on several innovative approaches to understand the causes and identify effective treatment and prevention methods for osteoarthritis. Through a public/ private partnership, researchers are identifying biomarkers for osteoarthritis to help develop and test new drugs. Imaging studies designed to better identify joint disorders and assess their progression are taking place as well.

Some genetic and behavioral studies are focusing on factors that may lead to osteoarthritis. Researchers recently found that daughters of women who have knee osteoarthritis have a significant increase in cartilage breakdown, thus making them more susceptible to disease. This finding has important implications for identifying people who are susceptible to osteoarthritis. Other studies of risk factors for osteoarthritis have identified excessive weight and lack of exercise as contributing factors to knee and hip disability.

Researchers are working to understand what role certain enzymes play in the breakdown of joint cartilage in osteoarthritis and are testing drugs that block the action of these enzymes.

Studies of injuries in young adults show that those who have had a previous joint injury are more likely to develop osteoarthritis. These studies underscore the need for increased education about joint injury prevention and use of proper sports equipment.



Systemic Lupus Erythematosus

Researchers are looking at how genetic, environmental, and hormonal factors influence the development of systemic lupus erythematosus. They are trying to find out why lupus is more common in certain populations, and they have made progress in identifying the genes that may be responsible for lupus. Researchers also continue to study the cellular and molecular basis of autoimmune disorders such as lupus. Promising areas of research on treatment include biologic agents; newer, more selective drugs that suppress the immune system; and bone transplants to correct immune abnormalities. Contrary to the widely held belief that estrogens can make the disease worse, clinical studies are revealing that it may be safe to use estrogens for hormone replacement therapy and birth control in women with lupus.



Scleroderma

Current studies on scleroderma are focusing on overproduction of collagen, blood vessel injury, and abnormal immune system activity. Researchers hope to discover how these three elements interact to cause and promote scleroderma. In one study, researchers found evidence of fetal cells within the blood and skin lesions of women who had been pregnant years before developing scleroderma. The study suggests that fetal cells may play a role in scleroderma by fostering the maturation of immune cells that promote the overproduction of collagen. Scientists are continuing to study the implications of this finding.

Treatment studies are underway as well. One study in particular is looking at the effectiveness of oral collagen in treating scleroderma.



Fibromyalgia

Scientists are looking at the basic causes of chronic pain and the health status of young women affected by fibromyalgia. The effectiveness of behavior therapy, acupuncture, and some alternative medical approaches for dealing with pain and loss of sleep are being tested. Researchers are also studying whether certain genes contribute to this disease.



Spondyloarthropathies

Researchers are working to understand the genetic and environmental causes of spondyloarthropathies, which include ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease, and reactive arthritis (Reiter's syndrome), as well as related conditions of the eye. They are also looking at new imaging methods that will help with early and accurate diagnosis, guide treatment, and detect responses to treatment. Research on new treatments is also underway.

The Health Partnership Program: A Local Diversity Outreach Initiative in the Rheumatic Diseases Where Can People Find More Information About Arthritis and Rheumatic Diseases?

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institutes of Health
1 AMS Circle
Bethesda, MD 20892-3675
Phone: 301-495-4484 or
877-22-NIAMS (226-4267) (free of charge)
TTY: 301-565-2966
Fax: 301-718-6366
E-mail: niamsinfo@mail.nih.gov
www.niams.nih.gov
NIAMS provides information about various forms of arthritis and rheumatic diseases and bone,

muscle, joint, and skin diseases. It distributes patient and professional education materials and refers people to other sources of information. Additional information and updates can be found on the NIAMS Web site. Listings of clinical trials recruiting patients who have or are at risk of developing a rheumatic disease can be found at www.ClinicalTrials.gov.

Acknowledgments

The NIAMS gratefully acknowledges the assistance of Barri Fessler, M.D., Cleveland Clinic Foundation, OH; John H. Klippel, M.D., Arthritis Foundation, Washington, DC; Reva Lawrence, M.P.H., NIAMS, NIH; Eric Matteson, M.D., Mayo Clinic, Rochester, MN; and Barbara Mittleman, M.D., NIAMS, NIH in the preparation and review of the current and earlier versions of this fact sheet.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. The National Institute of Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse is a public service sponsored by the NIAMS that provides health information and information sources. Additional information can be found on the NIAMS Web site at www.niams.nih.gov.

This fact sheet is not copyrighted. Readers are encouraged to duplicate and distribute as many copies as needed.

Additional copies of this fact sheet are available from

National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS) Information Clearinghouse
National Institutes of Health (NIH)
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Peripheral neuropathy describes damage to the peripheral nervous system, the vast communications network that transmits information from the brain and spinal cord (the central nervous system) to every other part of the body. Peripheral nerves also send sensory information back to the brain and spinal cord, such as a message that the feet are cold or a finger is burned. Damage to the peripheral nervous system interferes with these vital connections. Like static on a telephone line, peripheral neuropathy distorts and sometimes interrupts messages between the brain and the rest of the body.

Because every peripheral nerve has a highly specialized function in a specific part of the body, a wide array of symptoms can occur when nerves are damaged. Some people may experience temporary numbness, tingling, and pricking sensations (paresthesia), sensitivity to touch, or muscle weakness. Others may suffer more extreme symptoms, including burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction. People may become unable to digest food easily, maintain safe levels of blood pressure, sweat normally, or experience normal sexual function. In the most extreme cases, breathing may become difficult or organ failure may occur.

Some forms of neuropathy involve damage to only one nerve and are called mononeuropathies. More often though, multiple nerves affecting all limbs are affected-called polyneuropathy. Occasionally, two or more isolated nerves in separate areas of the body are affected-called mononeuritis multiplex.

In acute neuropathies, such as Guillain-Barré syndrome, symptoms appear suddenly, progress rapidly, and resolve slowly as damaged nerves heal. In chronic forms, symptoms begin subtly and progress slowly. Some people may have periods of relief followed by relapse. Others may reach a plateau stage where symptoms stay the same for many months or years. Some chronic neuropathies worsen over time, but very few forms prove fatal unless complicated by other diseases. Occasionally the neuropathy is a symptom of another disorder.

In the most common forms of polyneuropathy, the nerve fibers (individual cells that make up the nerve) most distant from the brain and the spinal cord malfunction first. Pain and other symptoms often appear symmetrically, for example, in both feet followed by a gradual progression up both legs. Next, the fingers, hands, and arms may become affected, and symptoms can progress into the central part of the body. Many people with diabetic neuropathy experience this pattern of ascending nerve damage.



How are the peripheral neuropathies classified?

More than 100 types of peripheral neuropathy have been identified, each with its own characteristic set of symptoms, pattern of development, and prognosis. Impaired function and symptoms depend on the type of nerves-motor, sensory, or autonomic-that are damaged. Motor nerves control movements of all muscles under conscious control, such as those used for walking, grasping things, or talking. Sensory nerves transmit information about sensory experiences, such as the feeling of a light touch or the pain resulting from a cut. Autonomic nerves regulate biological activities that people do not control consciously, such as breathing, digesting food, and heart and gland functions. Although some neuropathies may affect all three types of nerves, others primarily affect one or two types. Therefore, doctors may use terms such as predominately motor neuropathy, predominately sensory neuropathy, sensory-motor neuropathy, or autonomic neuropathy to describe a patient's condition.



What are the symptoms of peripheral nerve damage?

Symptoms are related to the type of affected nerve and may be seen over a period of days, weeks, or years. Muscle weakness is the most common symptom of motor nerve damage. Other symptoms may include painful cramps and fasciculations (uncontrolled muscle twitching visible under the skin), muscle loss, bone degeneration, and changes in the skin, hair, and nails. These more general degenerative changes also can result from sensory or autonomic nerve fiber loss.

Sensory nerve damage causes a more complex range of symptoms because sensory nerves have a wider, more highly specialized range of functions. Larger sensory fibers enclosed in myelin (a fatty protein that coats and insulates many nerves) register vibration, light touch, and position sense. Damage to large sensory fibers lessens the ability to feel vibrations and touch, resulting in a general sense of numbness, especially in the hands and feet. People may feel as if they are wearing gloves and stockings even when they are not. Many patients cannot recognize by touch alone the shapes of small objects or distinguish between different shapes. This damage to sensory fibers may contribute to the loss of reflexes (as can motor nerve damage). Loss of position sense often makes people unable to coordinate complex movements like walking or fastening buttons, or to maintain their balance when their eyes are shut. Neuropathic pain is difficult to control and can seriously affect emotional well-being and overall quality of life. Neuropathic pain is often worse at night, seriously disrupting sleep and adding to the emotional burden of sensory nerve damage.

Smaller sensory fibers without myelin sheaths transmit pain and temperature sensations. Damage to these fibers can interfere with the ability to feel pain or changes in temperature. People may fail to sense that they have been injured from a cut or that a wound is becoming infected. Others may not detect pains that warn of impending heart attack or other acute conditions. (Loss of pain sensation is a particularly serious problem for people with diabetes, contributing to the high rate of lower limb amputations among this population.) Pain receptors in the skin can also become oversensitized, so that people may feel severe pain (allodynia) from stimuli that are normally painless (for example, some may experience pain from bed sheets draped lightly over the body).

Symptoms of autonomic nerve damage are diverse and depend upon which organs or glands are affected. Autonomic nerve dysfunction can become life threatening and may require emergency medical care in cases when breathing becomes impaired or when the heart begins beating irregularly. Common symptoms of autonomic nerve damage include an inability to sweat normally, which may lead to heat intolerance; a loss of bladder control, which may cause infection or incontinence; and an inability to control muscles that expand or contract blood vessels to maintain safe blood pressure levels. A loss of control over blood pressure can cause dizziness, lightheadedness, or even fainting when a person moves suddenly from a seated to a standing position (a condition known as postural or orthostatic hypotension).

Gastrointestinal symptoms frequently accompany autonomic neuropathy. Nerves controlling intestinal muscle contractions often malfunction, leading to diarrhea, constipation, or incontinence. Many people also have problems eating or swallowing if certain autonomic nerves are affected.



What causes peripheral neuropathy?

Peripheral neuropathy may be either inherited or acquired. Causes of acquired peripheral neuropathy include physical injury (trauma) to a nerve, tumors, toxins, autoimmune responses, nutritional deficiencies, alcoholism, and vascular and metabolic disorders. Acquired peripheral neuropathies are grouped into three broad categories: those caused by systemic disease, those caused by trauma from external agents, and those caused by infections or autoimmune disorders affecting nerve tissue. One example of an acquired peripheral neuropathy is trigeminal neuralgia (also known as tic douloureux), in which damage to the trigeminal nerve (the large nerve of the head and face) causes episodic attacks of excruciating, lightning-like pain on one side of the face. In some cases, the cause is an earlier viral infection, pressure on the nerve from a tumor or swollen blood vessel, or, infrequently, multiple sclerosis. In many cases, however, a specific cause cannot be identified. Doctors usually refer to neuropathies with no known cause as idiopathic neuropathies.

Physical injury (trauma) is the most common cause of injury to a nerve. Injury or sudden trauma, such as from automobile accidents, falls, and sports-related activities, can cause nerves to be partially or completely severed, crushed, compressed, or stretched, sometimes so forcefully that they are partially or completely detached from the spinal cord. Less dramatic traumas also can cause serious nerve damage. 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.

Systemic diseases - disorders that affect the entire body often cause peripheral neuropathy. These disorders may include: Metabolic and endocrine disorders. Nerve tissues are highly vulnerable to damage from diseases that impair the body's ability to transform nutrients into energy, process waste products, or manufacture the substances that make up living tissue. Diabetes mellitus, characterized by chronically high blood glucose levels, is a leading cause of peripheral neuropathy in the United States. About 60 percent to 70 percent of people with diabetes have mild to severe forms of nervous system damage.

Kidney disorders can lead to abnormally high amounts of toxic substances in the blood that can severely damage nerve tissue. A majority of patients who require dialysis because of kidney failure develop polyneuropathy. Some liver diseases also lead to neuropathies as a result of chemical imbalances.

Hormonal imbalances can disturb normal metabolic processes and cause neuropathies. For example, an underproduction of thyroid hormones slows metabolism, leading to fluid retention and swollen tissues that can exert pressure on peripheral nerves. Overproduction of growth hormone can lead to acromegaly, a condition characterized by the abnormal enlargement of many parts of the skeleton, including the joints. Nerves running through these affected joints often become entrapped.

Vitamin deficiencies and alcoholism can cause widespread damage to nerve tissue. Vitamins E, B1, B6, B12, and niacin are essential to healthy nerve function. Thiamine deficiency, in particular, is common among people with alcoholism because they often also have poor dietary habits. Thiamine deficiency can cause a painful neuropathy of the extremities. Some researchers believe that excessive alcohol consumption may, in itself, contribute directly to nerve damage, a condition referred to as alcoholic neuropathy.

Vascular damage and blood diseases can decrease oxygen supply to the peripheral nerves and quickly lead to serious damage to or death of nerve tissues, much as a sudden lack of oxygen to the brain can cause a stroke. Diabetes frequently leads to blood vessel constriction. Various forms of vasculitis (blood vessel inflammation) frequently cause vessel walls to harden, thicken, and develop scar tissue, decreasing their diameter and impeding blood flow. This category of nerve damage, in which isolated nerves in different areas are damaged, is called mononeuropathy multiplex or multifocal mononeuropathy.

Connective tissue disorders and chronic inflammation can cause direct and indirect nerve damage. When the multiple layers of protective tissue surrounding nerves become inflamed, the inflammation can spread directly into nerve fibers. Chronic inflammation also leads to the progressive destruction of connective tissue, making nerve fibers more vulnerable to compression injuries and infections. Joints can become inflamed and swollen and entrap nerves, causing pain.

Cancers and benign tumors can infiltrate or exert damaging pressure on nerve fibers. Tumors also can arise directly from nerve tissue cells. Widespread polyneuropathy is often associated with the neurofibromatoses, genetic diseases in which multiple benign tumors grow on nerve tissue. Neuromas, benign masses of overgrown nerve tissue that can develop after any penetrating injury that severs nerve fibers, generate very intense pain signals and sometimes engulf neighboring nerves, leading to further damage and even greater pain. Neuroma formation can be one element of a more widespread neuropathic pain condition called complex regional pain syndrome or reflex sympathetic dystrophy syndrome, which can be caused by traumatic injuries or surgical trauma. Paraneoplastic syndromes, a group of rare degenerative disorders that are triggered by a person's immune system response to a cancerous tumor, also can indirectly cause widespread nerve damage.

Repetitive stress frequently leads to entrapment neuropathies, a special category of compression injury. Cumulative damage can result from repetitive, forceful, awkward activities that require flexing of any group of joints for prolonged periods. The resulting irritation may cause ligaments, tendons, and muscles to become inflamed and swollen, constricting the narrow passageways through which some nerves pass. These injuries become more frequent during pregnancy, probably because weight gain and fluid retention also constrict nerve passageways.

Toxins can also cause peripheral nerve damage. People who are exposed to heavy metals (arsenic, lead, mercury, thallium), industrial drugs, or environmental toxins frequently develop neuropathy. Certain anticancer drugs, anticonvulsants, antiviral agents, and antibiotics have side effects that can include peripheral nerve damage, thus limiting their long-term use.

Infections and autoimmune disorders can cause peripheral neuropathy. Viruses and bacteria that can attack nerve tissues include herpes varicella-zoster (shingles), Epstein-Barr virus, cytomegalovirus, and herpes simplex-members of the large family of human herpes viruses. These viruses severely damage sensory nerves, causing attacks of sharp, lightning-like pain. Postherpetic neuralgia often occurs after an attack of shingles and can be particularly painful.

The human immunodeficiency virus (HIV), which causes AIDS, also causes extensive damage to the central and peripheral nervous systems. The virus can cause several different forms of neuropathy, each strongly associated with a specific stage of active immunodeficiency disease. A rapidly progressive, painful polyneuropathy affecting the feet and hands is often the first clinically apparent sign of HIV infection.

Lyme disease, diphtheria, and leprosy are bacterial diseases characterized by extensive peripheral nerve damage. Diphtheria and leprosy are now rare in the United States, but Lyme disease is on the rise. It can cause a wide range of neuropathic disorders, including a rapidly developing, painful polyneuropathy, often within a few weeks after initial infection by a tick bite.

Viral and bacterial infections can also cause indirect nerve damage by provoking conditions referred to as autoimmune disorders, in which specialized cells and antibodies of the immune system attack the body's own tissues. These attacks typically cause destruction of the nerve's myelin sheath or axon (the long fiber that extends out from the main nerve cell body).

Some neuropathies are caused by inflammation resulting from immune system activities rather than from direct damage by infectious organisms. Inflammatory neuropathies can develop quickly or slowly, and chronic forms can exhibit a pattern of alternating remission and relapse. Acute inflammatory demyelinating neuropathy, better known as Guillain-Barré syndrome, can damage motor, sensory, and autonomic nerve fibers. Most people recover from this syndrome although severe cases can be life threatening. Chronic inflammatory demyelinating polyneuropathy (CIDP), generally less dangerous, usually damages sensory and motor nerves, leaving autonomic nerves intact. Multifocal motor neuropathy is a form of inflammatory neuropathy that affects motor nerves exclusively; it may be chronic or acute.

Inherited forms of peripheral neuropathy are caused by inborn mistakes in the genetic code or by new genetic mutations. Some genetic errors 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 most common inherited neuropathies are a group of disorders collectively referred to as Charcot-Marie-Tooth disease. These neuropathies result from flaws in genes responsible for manufacturing neurons or the myelin sheath. Hallmarks of typical Charcot-Marie-Tooth disease include extreme weakening and wasting of muscles in the lower legs and feet, gait abnormalities, loss of tendon reflexes, and numbness in the lower limbs.



What treatments are available?

No medical treatments now exist that can cure inherited peripheral neuropathy. However, there are therapies for many other forms. Any underlying condition is treated first, followed by symptomatic treatment. Peripheral nerves have the ability to regenerate, as long as the nerve cell itself has not been killed. Symptoms often can be controlled, and eliminating the causes of specific forms of neuropathy often can prevent new damage.

In general, adopting healthy habits-such as maintaining optimal weight, avoiding exposure to toxins, following a physician-supervised exercise program, eating a balanced diet, correcting vitamin deficiencies, and limiting or avoiding alcohol consumption-can reduce the physical and emotional effects of peripheral neuropathy. Active and passive forms of exercise can reduce cramps, improve muscle strength, and prevent muscle wasting in paralyzed limbs. Various dietary strategies can improve gastrointestinal symptoms. Timely treatment of injury can help prevent permanent damage. Quitting smoking is particularly important because smoking constricts the blood vessels that supply nutrients to the peripheral nerves and can worsen neuropathic symptoms. Self-care skills such as meticulous foot care and careful wound treatment in people with diabetes and others who have an impaired ability to feel pain can alleviate symptoms and improve quality of life. Such changes often create conditions that encourage nerve regeneration.

Systemic diseases frequently require more complex treatments. Strict control of blood glucose levels has been shown to reduce neuropathic symptoms and help people with diabetic neuropathy avoid further nerve damage. Inflammatory and autoimmune conditions leading to neuropathy can be controlled in several ways. Immunosuppressive drugs such as prednisone, cyclosporine, or azathioprine may be beneficial. Plasmapheresis-a procedure in which blood is removed, cleansed of immune system cells and antibodies, and then returned to the body-can limit inflammation or suppress immune system activity. High doses of immunoglobulins, proteins that function as antibodies, also can suppress abnormal immune system activity.

Neuropathic pain is often difficult to control. Mild pain may sometimes be alleviated by analgesics sold over the counter. Several classes of drugs have recently proved helpful to many patients suffering from more severe forms of chronic neuropathic pain. These include mexiletine, a drug developed to correct irregular heart rhythms (sometimes associated with severe side effects); several antiepileptic drugs, including gabapentin, phenytoin, and carbamazepine; and some classes of antidepressants, including tricyclics such as amitriptyline. Injections of local anesthetics such as lidocaine or topical patches containing lidocaine may relieve more intractable pain. In the most severe cases, doctors can surgically destroy nerves; however, the results are often temporary and the procedure can lead to complications.

Mechanical aids can help reduce pain and lessen the impact of physical disability. Hand or foot braces can compensate for muscle weakness or alleviate nerve compression. Orthopedic shoes can improve gait disturbances and help prevent foot injuries in people with a loss of pain sensation. If breathing becomes severely impaired, mechanical ventilation can provide essential life support.

Surgical intervention often can provide immediate relief from mononeuropathies caused by compression or entrapment injuries. Repair of a slipped disk can reduce pressure on nerves where they emerge from the spinal cord; the removal of benign or malignant tumors can also alleviate damaging pressure on nerves. Nerve entrapment often can be corrected by the surgical release of ligaments or tendons.



What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS), a component of the Federal government's National Institutes of Health (NIH) within the U.S. Department of Health and Human Services, has primary responsibility for research on peripheral neuropathy. Current research projects funded by the NINDS involve investigations of genetic factors associated with hereditary neuropathies, studies of biological mechanisms involved in diabetes-associated neuropathies, efforts to gain greater understanding of how the immune system contributes to peripheral nerve damage, and efforts to develop new therapies for neuropathic symptoms.

Because specific genetic defects have been identified for only a fraction of the known hereditary neuropathies, the Institute sponsors studies to identify other genetic defects that may cause these conditions. Presymptomatic diagnosis may lead to therapies for preventing nerve damage before it occurs, and gene replacement therapies could be developed to prevent or reduce cumulative nerve damage.

Several NINDS-funded studies are investigating some of the possible biological mechanisms responsible for the many forms of neuropathy, including the autonomic neuropathies that affect people with diabetes. The Institute also is funding studies to measure the frequency and progression rates of diabetic neuropathies, examine the effects of these disorders on quality of life, and identify factors that may put certain individuals at greater risk for developing diabetes-associated neuropathies.

Scientists have found that the destructive effects of abnormal immune system activity cause many neuropathies for which a cause could not previously be identified. However, the exact biological mechanisms that lead to this nerve damage are not yet well understood. Many NINDS-sponsored studies are studying inflammatory neuropathies, both in research animals and in humans, to clarify these mechanisms so that therapeutic interventions can be developed. Neuropathic pain is a primary target of NINDS-sponsored studies aimed at developing more effective therapies for symptoms of peripheral neuropathy. Some scientists hope to identify substances that will block the brain chemicals that generate pain signals, while others are investigating the pathways by which pain signals reach the brain.

Studies of neurotrophic factors represent one of the most promising areas of research aimed at finding new, more effective treatments for peripheral neuropathies. These substances, produced naturally by the body, protect neurons from injury and encourage their survival. Neurotrophic factors also help maintain normal function in mature nerve cells, and some stimulate axon regeneration. Several NINDS-sponsored studies seek to learn more about the effects of these powerful chemicals on the peripheral nervous system and may eventually lead to treatments that can reverse nerve damage and cure peripheral nerve disorders.




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