Peripheral neuropathy is a condition that occurs when the nerves located outside the brain and spinal cord become damaged, causing a range of uncomfortable sensations and sometimes affecting the body’s ability to control certain functions automatically.

Understanding Peripheral Neuropathy

The nervous system in your body works like a complex highway, constantly carrying messages back and forth between your brain and the rest of your body. When this messaging system works properly, you can feel sensations, move muscles, and your body can automatically control things like digestion and heart rate without you having to think about it. Peripheral neuropathy happens when the nerves outside your brain and spinal cord, called peripheral nerves, become damaged or start malfunctioning. These peripheral nerves are responsible for sending all kinds of information, including telling you when your feet are cold, helping you move your arms and legs, and controlling automatic body functions.^[1]

The term “peripheral” comes from an ancient Greek word meaning “around,” referring to nerves that are away from the central nervous system. Meanwhile, “neuropathy” combines two Greek words: “neuron” meaning nerve, and “pathos” meaning affliction or condition. Healthcare providers sometimes use the terms “neuropathy” and polyneuropathy, which means disease of many nerves, to describe the same condition. Because peripheral nerves are the farthest from the central nervous system, they often show the earliest and most severe effects when something goes wrong.^[2]

Epidemiology

Peripheral neuropathy is surprisingly common around the world. Globally, about 2.4% of people have some form of peripheral neuropathy. However, this percentage increases significantly as people get older. Among people aged 45 and older, the rate rises to between 5% and 7%. In the general population, the prevalence ranges from 1% to 7%, with higher rates appearing in those over 50 years old.^[2][5]

In the United Kingdom, it is estimated that almost 1 in 10 people aged 55 or over are affected by peripheral neuropathy. This makes it one of the most common neurologic problems that family doctors encounter in their daily practice. The condition can affect anyone regardless of age, sex, race, ethnicity, or personal circumstances, though certain groups face higher risks depending on the specific type of neuropathy and underlying health conditions they may have.^[4][1]

Causes

Peripheral neuropathy can result from many different causes, and understanding what triggered the nerve damage is important for treatment. In the United Kingdom and United States, diabetes is the most common cause of peripheral neuropathy. Over time, high blood sugar levels associated with diabetes can damage the tiny nerves and the small blood vessels that nourish them. This type of nerve damage, known as diabetic polyneuropathy, affects about 25% to 50% of people with diabetes, depending on factors such as how long they’ve had diabetes, their age, and how well their blood sugar is controlled.^[4][12]

Beyond diabetes, peripheral neuropathy has many other possible causes. Traumatic injuries can directly damage nerves, leading to neuropathy. Infections, including viral infections like shingles, can also cause nerve damage. Exposure to toxins or heavy alcohol use is another significant cause. Some people inherit conditions that make them prone to peripheral neuropathy, such as Charcot-Marie-Tooth disease, which affects nerves in the arms, hands, legs, and feet. Other inherited conditions include Friedreich ataxia and giant axonal neuropathy.^[1]

Metabolic problems, including low levels of vitamins, particularly vitamin B12, can lead to peripheral neuropathy. Certain medications, including some used for chemotherapy, heart conditions, and blood pressure, can cause nerve damage as a side effect. Health conditions such as rheumatoid arthritis, lupus, kidney disease, Lyme disease, hepatitis, and thyroid problems can also trigger peripheral neuropathy. Additionally, conditions causing poor blood flow to the legs, such as peripheral arterial disease, can contribute to nerve damage.^[1][12]

Interestingly, in about 25% to 46% of cases, the cause of peripheral neuropathy cannot be identified. These cases are called idiopathic peripheral neuropathy, and they become more common as people age. This means that even with thorough testing, doctors sometimes cannot pinpoint exactly what caused the nerve damage.^[5][12]

Risk Factors

Several factors can increase a person’s risk of developing peripheral neuropathy. Age is one of the most significant risk factors, with the condition becoming more common as people grow older. This is partly because peripheral neuropathy is common with certain age-related diseases. Having a family history of neuropathy, such as familial diabetes or inherited nerve conditions, also raises the risk.^[2][5]

People with certain medical conditions face higher risks. Those with diabetes, particularly if it’s poorly controlled, are at significantly increased risk. Individuals with rheumatoid arthritis, lupus, kidney disease, or thyroid dysfunction are also more vulnerable. Poor nutrition or malnourishment can contribute to nerve damage by depriving the body of essential vitamins and nutrients needed for nerve health.^[5]

Lifestyle factors play an important role as well. Excessive alcohol use is a well-known risk factor for peripheral neuropathy. Long-term exposure to cold temperatures or toxic chemicals can damage nerves over time. People who smoke are at higher risk because smoking interferes with circulation, which can worsen nerve problems. Certain occupations or activities that involve repetitive movements or prolonged pressure on nerves, such as using crutches or wearing a cast, can also increase risk.^[12]

Specific medications are known to increase the risk of developing neuropathy. These include platinum-based chemotherapy drugs, taxanes, vinca alkaloids, thalidomide, and certain other treatments. People undergoing cancer treatment with these medications should be monitored carefully for signs of nerve damage. Additionally, people with certain types of cancer, including lung, breast, ovarian, myeloma, lymphoma, Hodgkin’s disease, and testicular cancer, face higher risks of developing peripheral neuropathy.^[5]

Symptoms

The symptoms of peripheral neuropathy vary widely depending on which nerves are affected. The peripheral nervous system includes three main types of nerves: sensory nerves that transmit sensations like touch, temperature, and pain; motor nerves that control muscle movement; and autonomic nerves that regulate automatic functions like blood pressure, heart rate, digestion, and bladder control. Most cases of neuropathy affect all three types to varying degrees, though some predominantly affect one or two types.^[1][3]

Early peripheral neuropathy often presents with sensory changes that are usually progressive. The most common early symptoms include numbness and tingling sensations in the feet or hands. These sensations are often described as feeling like “pins and needles.” People may experience a gradual onset of prickling or tingling in their feet or hands, and these sensations can spread upward into the legs and arms over time. Many people describe feeling as if they’re wearing an invisible glove or stocking, which is why doctors refer to this pattern as “stocking and glove” distribution.^[1][5]

Pain is another frequent symptom. People with peripheral neuropathy often describe their pain as sharp, jabbing, throbbing, stabbing, or burning. This pain can be extremely uncomfortable and is frequently worse at night, making it difficult to sleep. Some people develop extreme sensitivity to touch, where even light contact with clothing or bedsheets can cause significant discomfort. Others experience pain during activities that shouldn’t normally cause pain.^[1]

As peripheral neuropathy progresses, motor symptoms may develop. These include muscle weakness, particularly in the feet or hands. Some people experience difficulty walking or maintaining balance and coordination. Clumsiness becomes more common, and individuals may notice they’re dropping things more often. Loss of reflexes can occur, and in severe cases, muscle wasting may develop in the hands and feet. Cramping, especially in the hands, feet, or calf muscles, can also occur.^[1][4]

When autonomic nerves are affected, symptoms can include problems with blood pressure regulation, particularly dizziness when standing up from a bed or chair. Digestive issues may develop, including the slow movement of food through the stomach. Some people experience bladder problems or sexual dysfunction. These autonomic symptoms can significantly impact quality of life.^[1]

The pattern and location of symptoms can vary. Most neuropathies are “length-dependent,” meaning the farthest nerve endings from the brain, particularly those in the feet, are where symptoms develop first or are most severe. In severe cases, symptoms can spread upward toward more central parts of the body. However, in some types of neuropathy, symptoms might start around the torso or move around to different parts of the body.^[3]

Prevention

While not all cases of peripheral neuropathy can be prevented, several strategies can reduce your risk or slow progression if you’re already at risk. Managing underlying health conditions is one of the most important preventive measures. For people with diabetes, maintaining blood sugar levels within the target range is crucial. Good diabetes control can help prevent peripheral neuropathy from developing or slow its progression if it has already started. This involves following your treatment plan, monitoring blood sugar regularly, eating a healthy diet, and staying active.^[4]

Lifestyle modifications play a significant role in prevention. Quitting smoking is essential, as smoking interferes with blood circulation and increases the risk of developing neuropathy while making existing symptoms worse. Limiting or eliminating alcohol consumption is another important step, as excessive alcohol use is a known cause of nerve damage. For people who drink heavily, stopping alcohol use and ensuring proper nutrition, including vitamin supplementation if needed, can help prevent further damage.^[12]

Maintaining proper nutrition supports nerve health. Eating a balanced diet rich in vitamin B12 and other essential nutrients helps protect nerves. Foods high in thiamine, protein, and antioxidants are particularly beneficial. If you have nutritional deficiencies, taking supplements under medical guidance can help prevent nerve damage. Some people may benefit from vitamin B12 injections or tablets if they have a deficiency.^[4]

Physical activity is valuable for prevention. Regular exercise improves circulation throughout the body, including to the peripheral nerves. Exercise also helps control blood sugar levels, maintain a healthy weight, and improve overall fitness. Even moderate exercise, such as walking three times a week for 30 to 60 minutes, can provide significant benefits for nerve health.^[12]

Protecting yourself from nerve injuries is another preventive strategy. This includes avoiding repetitive movements that put pressure on nerves, maintaining good posture, taking breaks during activities that stress certain body parts, and being careful to avoid injuries. Long-term exposure to toxic chemicals should be avoided when possible, and appropriate safety equipment should be used when working with potentially harmful substances.^[5]

For people at high risk of peripheral neuropathy, such as those with diabetes or receiving certain chemotherapy treatments, regular check-ups are important. These allow healthcare providers to monitor nerve function and detect early signs of neuropathy. Early detection gives the best chance of limiting damage and preventing complications. People taking medications known to cause neuropathy should be monitored closely, and alternative medications should be considered if nerve symptoms develop.^[4][5]

Pathophysiology

To understand how peripheral neuropathy affects the body, it helps to know how neurons, the key cells that make up nerves, are structured and function. Neurons send and relay signals throughout your nervous system using both electrical and chemical signals. Each neuron consists of several parts: the cell body, which is the main part of the cell; the axon, a long arm-like extension that carries signals away from the cell body; and dendrites, small branch-like extensions on the cell body that receive signals from other neurons.^[2]

Many nerve fibers are covered by myelin, a thin protective layer made of fatty compounds. Myelin acts like insulation around an electrical wire, allowing signals to travel quickly and efficiently along the nerve. At the end of the axon are finger-like extensions called synapses, where electrical signals are converted into chemical signals that can be passed to nearby nerve cells. This complex system allows your body to transmit information rapidly from one area to another.^[2]

In peripheral neuropathy, damage can occur to different parts of the neuron. The injury might affect the cell body itself, the axon that carries signals, the myelin sheath that protects the nerve, or a combination of these structures. The pathophysiology of peripheral neuropathy results from injury to either small-diameter or large-diameter nerve fibers, and the type of fiber affected influences the symptoms experienced.^[5]

When nerves are damaged, the nervous system’s ability to communicate is disrupted in several ways. First, signals that should be sent may not be transmitted at all, leading to numbness or loss of sensation. Second, signals may be sent when they shouldn’t be, causing abnormal sensations or pain even when there’s no injury present. Third, errors can change the messages being sent, causing the body to misinterpret signals. These disruptions explain the wide variety of symptoms people experience with peripheral neuropathy.^[3]

The mechanisms of nerve damage vary depending on the cause. In diabetic neuropathy, elevated blood sugar levels are thought to damage both the nerves themselves and the tiny blood vessels that supply oxygen and nutrients to the nerves. This dual damage leads to progressive nerve dysfunction. In cases where neuropathy is caused by toxins or certain medications, these substances can directly poison nerve cells or interfere with their normal function. Physical injuries can cause mechanical damage to nerve fibers, disrupting their structure and ability to transmit signals.^[12]

Nutritional deficiencies, particularly of vitamin B12, affect nerve health because these nutrients are essential for maintaining the myelin sheath and supporting normal nerve function. Without adequate nutrition, nerves cannot repair themselves properly, leading to progressive damage. Inherited forms of neuropathy involve genetic defects that affect how neurons are built or maintained, leading to gradual deterioration of nerve function over time.^[4]

The pattern of nerve damage in most cases of peripheral neuropathy follows a “length-dependent” pattern. This means the longest nerves in the body, which reach all the way to the feet and hands, are affected first and most severely. Scientists believe this happens because these long nerves have the greatest metabolic demands and are most vulnerable to disruptions in blood supply or nutritional support. As the condition progresses, shorter nerves become involved, causing symptoms to spread upward from the feet and hands toward the body’s center.^[3]