Peripheral Neuropathy: Causes, Symptoms, Blood Tests and Treatment

Peripheral neuropathy is damage to the nerves outside the brain and spinal cord. It most often starts as numbness, tingling, burning or pain in both feet, sometimes later in the hands, in a "stocking and glove" pattern. It can also cause weakness, poor balance and problems with sweating, digestion or blood pressure.

It is common: depending on the study, 1% to 7% of the general population is affected, and about 6% of adults aged 50 and over. Diabetes is the leading cause in the US, but several other causes are treatable, so a short set of blood tests (glucose or A1c, vitamin B12 with methylmalonic acid, TSH, a kidney and liver panel, and serum protein electrophoresis with immunofixation) is the first step to find the cause.

Key takeaways

• Peripheral neuropathy usually starts in the toes and feet and moves up slowly; it is often worse at night.
• Diabetes is the most common cause, but in 25% to 46% of cases no cause is found even after testing.
• The American Academy of Neurology names blood glucose, vitamin B12 with methylmalonic acid, and serum protein immunofixation as the screening tests with the highest yield.
• Nerve conduction studies and EMG confirm the diagnosis and show whether the nerve fibers or their insulating coat are damaged.
• Treating the cause can stop or reverse some neuropathies; duloxetine, pregabalin or amitriptyline ease nerve pain, while opioids are not recommended.

What is peripheral neuropathy?

Peripheral nerves carry messages between the brain and spinal cord and the rest of the body. The National Institute of Neurological Disorders and Stroke (NINDS) describes three types: sensory nerves (touch, temperature, vibration, pain), motor nerves (muscle movement) and autonomic nerves (heartbeat, blood pressure, digestion, sweating).

More than 100 types of peripheral neuropathy have been identified, and most affect all three kinds of fibers to some degree. Most are "length-dependent": the longest nerves, which reach the feet, fail first.

Polyneuropathy affects many nerves on both sides; distal symmetric polyneuropathy is the most common form. Mononeuropathy affects a single nerve, as in carpal tunnel syndrome; see our guide to nerve compression syndromes. Small fiber neuropathy affects only the thin fibers that carry pain and temperature, so standard nerve tests can be normal.

How many people have neuropathy?

A review in American Family Physician puts the prevalence of peripheral neuropathy at 1% to 7% of the general population, with higher rates after age 50. In the Dutch Rotterdam Study, 6.0% of adults aged 50 and over had chronic axonal polyneuropathy, rising with age. NINDS says peripheral neuropathy affects millions of people in the US.

In people with diabetes, it is far more frequent. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) states that up to half of people with diabetes have peripheral neuropathy, and the American Diabetes Association (ADA) notes that up to 50% of cases cause no symptoms at all.

Peripheral neuropathy causes

NINDS calls diabetes the leading cause of peripheral neuropathy in the US. Many other conditions can damage nerves, and some are easy to miss:

• Diabetes and prediabetes. High blood sugar over a long time damages nerves; see our guide to diabetes symptoms, causes and treatment. In a University of Michigan study, polyneuropathy affected 3.8% of lean adults but 29% of obese adults with prediabetes and 34.6% with diabetes.
• Vitamin deficiencies and excess. NINDS lists vitamin B12 deficiency and too much vitamin B6 as the best-known vitamin-related causes; MedlinePlus adds low vitamin B1. See low vitamin B12 and nerve damage and the vitamin B6 blood test. The ADA also lists acquired copper deficiency after weight-loss surgery.
• Alcohol. Long-term heavy drinking can damage nerves.
• Thyroid, kidney and liver disease. An underactive thyroid (hypothyroidism) can cause neuropathy, and NINDS notes that most people on dialysis develop some form of it.
• Medicines. Some drugs for cancer, HIV, infections, heart disease, seizures and alcohol dependence can damage nerves. After chemotherapy, a meta-analysis found neuropathy in 68.1% of patients in the first month and 30% six months or more later.
• Blood protein disorders. An abnormal antibody made by a single clone of plasma cells (a monoclonal protein) can be a sign of monoclonal gammopathy of undetermined significance (MGUS), amyloidosis or multiple myeloma, all linked to neuropathy.
• Infections. HIV, hepatitis C, shingles and Lyme disease can affect nerves.
• Autoimmune and inflammatory diseases, such as lupus, rheumatoid arthritis, inflammation of blood vessels (vasculitis), Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP).
• Toxins such as lead, mercury and solvents, and pressure on a nerve.
• Inherited neuropathies. Charcot-Marie-Tooth disease is the most common inherited neurological disorder, though genetic causes are rare overall.

Even after a full workup, 25% to 46% of cases remain idiopathic, meaning no cause is found.

Neuropathy symptoms

Symptoms depend on which fibers are damaged and can develop over days, weeks or years; NINDS notes they are rarely life-threatening.

Sensory symptoms

• tingling, "pins and needles" or numbness, often starting in the toes;
• burning, sharp or deep pain;
• pain from a light touch, such as bedsheets on the feet (allodynia);
• loss of vibration and position sense, which makes balance harder in the dark or with eyes closed;
• not feeling heat, cold or a cut, which allows injuries to go unnoticed.

Motor symptoms

Weakness, cramps, twitching under the skin and, over time, thinner muscles. Weakness and poor balance raise the risk of falls and fractures.

Autonomic symptoms

Too much or too little sweating, heat intolerance, dizziness when standing up, feeling full quickly, diarrhea or constipation, and bladder or sexual problems.

Neuropathy in feet

NIDDK explains that reduced feeling can hide pressure points and injuries, leading to blisters and sores; in people with diabetes, slow healing and infection can lead to amputation of a toe, foot or part of a leg. For numbness limited to one spot, see our guide to a numb big toe.

How neuropathy affects sleep

Nerve pain often gets worse at night. NINDS notes that it can disrupt sleep, and NIDDK says diabetic neuropathy symptoms are often worse at night. A meta-analysis found restless legs syndrome, an urge to move the legs at rest, in about 21.5% of people with peripheral neuropathy. The American Academy of Neurology (AAN) asks doctors to check people with painful diabetic neuropathy for sleep and mood disorders and to treat them together with the pain.

How peripheral neuropathy is diagnosed

Diagnosis starts with a history (symptoms, alcohol, medicines, toxins, family history) and an exam of strength, reflexes and sensation. In people with diabetes, the ADA recommends checking for neuropathy at the diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes, then at least once a year, including pinprick or temperature, vibration with a 128-Hz tuning fork, and a yearly 10-gram monofilament test of the feet.

Neuropathy blood tests

The 2009 AAN practice parameter found that the blood tests with the highest yield are blood glucose, serum vitamin B12 with its metabolites (methylmalonic acid, with or without homocysteine), and serum protein immunofixation electrophoresis. If routine glucose tests do not show diabetes, a glucose tolerance test may be considered. The review in American Family Physician recommends a starting panel of:

• a complete blood count, for anemia and other blood changes;
• a comprehensive metabolic panel, which includes the kidney function panel and liver function tests;
• fasting blood glucose (see our guide to fasting glucose levels) and often an HbA1c test;
• a vitamin B12 blood test;
• a TSH blood test for thyroid function;
• serum protein electrophoresis (SPEP) with immunofixation, to look for a monoclonal protein (see our guide to protein electrophoresis results).

Depending on the story, doctors may add methylmalonic acid and homocysteine, a serum free light chain test, vitamin B1, B6 and copper levels, HIV and hepatitis C tests, inflammation and autoimmune markers, a celiac test, or genetic testing when neuropathy runs in the family.

Nerve conduction studies and EMG

A nerve conduction study places small electrodes on the skin and sends mild electrical pulses along a nerve to measure how fast and how strongly signals travel. An electromyography (EMG) needle exam records electrical activity inside muscles. Together, NINDS explains, they confirm nerve damage and show whether it comes from loss of the nerve fiber itself (axonal damage) or of its insulating myelin coat (demyelination, as in CIDP, where the immune system attacks the myelin sheath). That distinction narrows the list of causes.

Other tests

A skin biopsy, taken under local anesthesia, counts small nerve endings and detects small fiber neuropathy when nerve conduction studies are normal. Doctors may also order a sweat test (QSART), an MRI of the spine for a pinched nerve, or, rarely, a nerve biopsy.

Neuropathy lab workup: reference values

Ranges vary slightly between laboratories (MedlinePlus); compare with the range on your report.

How to read your results

• A fasting glucose of 100-125 mg/dL or an A1c of 5.7-6.4% (prediabetes) is linked to neuropathy and worth treating. Two abnormal results are needed to diagnose diabetes.
• A low B12 should be confirmed with methylmalonic acid: a high MMA indicates a true deficiency. If you take metformin, ask about B12: a meta-analysis of 31 studies found metformin users had about twice the risk of B12 deficiency (risk ratio 2.09) and recommended yearly checks.
• A high TSH points to hypothyroidism, which is treated with thyroid hormone.
• A high creatinine or a low eGFR suggests kidney disease, which can cause or worsen neuropathy.
• A monoclonal protein on immunofixation is not by itself a cancer diagnosis: it can come from MGUS as well as from myeloma, amyloidosis or lymphoma, so it needs follow-up with a specialist.
• If every test is normal, you may have idiopathic neuropathy or small fiber neuropathy; a nerve conduction study, skin biopsy or a neurologist referral is the next step.

Peripheral neuropathy treatment

NINDS explains that when the underlying cause is corrected, neuropathy can sometimes resolve as nerves recover and regrow. Treatment therefore has two parts: the cause and the symptoms.

Treating the cause

• Diabetes: the ADA recommends optimizing blood glucose to prevent or delay neuropathy in type 1 diabetes and to slow it in type 2, and managing weight, blood pressure and lipids.
• Vitamin B12 deficiency: vitamin B12 replacement, and stopping excess vitamin B6 supplements.
• Hypothyroidism: thyroid hormone replacement.
• Medicines: for chemotherapy, the American Society of Clinical Oncology (ASCO) asks doctors to consider delaying, reducing or changing treatment if neuropathy becomes intolerable.
• Immune neuropathies such as CIDP: intravenous immunoglobulin (IVIg), steroids, plasma exchange or other immune treatments.

Medicines for nerve pain

The 2022 AAN guideline and the ADA Standards of Care 2026 recommend four drug classes as first-line treatment of painful diabetic neuropathy:

• serotonin-norepinephrine reuptake inhibitors (SNRIs), such as duloxetine;
• gabapentinoids, such as pregabalin and gabapentin;
• tricyclic antidepressants, such as amitriptyline and nortriptyline;
• sodium channel blockers.

Their benefit is similar, so the choice depends on side effects and other health conditions. If one class fails, the AAN recommends trying a different one. In the UK OPTION-DM trial (130 patients), pain fell from 6.6 to 3.3 out of 10 with amitriptyline, duloxetine or pregabalin, and adding a second drug helped people who had not responded enough to one; the ADA now states that combinations can provide additional relief.

The ADA states that opioids, including tramadol and tapentadol, should not be used for diabetic nerve pain except in rare circumstances; NINDS also advises against them. Topical options include the capsaicin 8% patch, FDA-approved for painful diabetic neuropathy, and lidocaine patches, which can help nighttime foot pain but cannot be worn more than 12 hours a day. For painful chemotherapy-induced neuropathy, ASCO names duloxetine as the only agent with adequate evidence, with modest benefit.

Treatment options for numbness

Drugs ease pain but do not restore lost feeling, and NIDDK notes they do not reverse nerve damage. For numbness, the focus is on treating the cause, protecting the feet, physical therapy, and braces or orthopedic shoes. NINDS also mentions nerve stimulation (TENS), acupuncture and tai chi for some people.

Living with neuropathy: diet, exercise and foot care

Diet

No special diet cures neuropathy, but eating to keep blood sugar, weight and blood lipids in range helps protect nerves. In a small 20-week randomized pilot study in people with type 2 diabetes and painful neuropathy, a low-fat plant-based diet with weekly classes led to 6.4 kg of weight loss and a modest drop in pain compared with B12 supplements alone. Get enough vitamin B12, especially if you eat vegan, are over 75 or take metformin, and limit alcohol.

Exercise and walking

The ADA notes that exercise improves symptoms, balance and function in diabetic neuropathy, though the evidence is of low strength. Wear protective shoes and check your feet after each session.

Daily foot care

• Check your feet every day.
• Call your doctor right away about any foot problem.
• Ask about orthopedic shoes if weakness changes how you walk.
• Take off your shoes and socks at each medical visit so your feet are checked, and see a podiatrist if you have lost feeling.

Preventing peripheral neuropathy

NINDS lists ways to lower the risk or slow progression: manage diabetes and other conditions, eat well, exercise, keep a healthy weight, avoid toxins and heavy drinking, and quit smoking. The shingles vaccine, recommended for almost everyone over 50, prevents nerve pain after shingles.

When to see a doctor

See your doctor if you have:

• tingling, numbness, burning or pain in the feet or hands that lasts more than a few weeks;
• new weakness, tripping or falls;
• a foot sore, blister or color change you did not feel happen, especially with diabetes;
• symptoms while taking metformin or chemotherapy, or after weight-loss surgery.

Call 911 or go to the emergency room if weakness comes on quickly and worsens over hours or days, often starting in the feet and moving up the body, or if you have any trouble breathing. These can be signs of Guillain-Barré syndrome, which NINDS describes as starting suddenly and potentially affecting breathing, blood pressure and heart rate.

Latest scientific advances in peripheral neuropathy

New data on how common neuropathy is after 50

A 2026 report from the Rotterdam Study, using nerve conduction studies in every participant, found chronic axonal polyneuropathy in 6.0% of adults aged 50 and over and 3.8 new cases per 1,000 people per year. With aging, the authors expect prevalence to rise by 19% to 24% by 2050.

A new class of non-opioid pain medicine is being tested

Suzetrigine, which blocks the Nav1.8 sodium channel in pain-sensing nerves outside the brain, was approved by the FDA in January 2025 for moderate to severe acute pain. It is the first new non-opioid pain medicine approved in the US since 1998 and is now being tested in painful diabetic neuropathy: a phase 3 trial of about 1,100 adults comparing it with pregabalin and placebo (NCT06628908) and another of 734 adults against placebo (NCT07231419) are recruiting, with primary completion expected in 2027. It is not yet approved for neuropathy.

Exercise improves balance

A 2026 meta-analysis of 16 randomized trials (759 middle-aged and older adults with diabetic neuropathy) found that exercise training improved balance scores and shortened the Timed Up and Go test by about 1.7 seconds, although the certainty of evidence was low.

Which tests can help?

Tests often ordered when neuropathy is suspected:

• fasting glucose and HbA1c;
• vitamin B12 with methylmalonic acid, and TSH;
• a complete blood count, kidney and liver tests;
• serum protein electrophoresis with immunofixation;
• a nerve conduction study and EMG.

Glossary

• Polyneuropathy: damage to many peripheral nerves, usually on both sides of the body.
• Mononeuropathy: damage to a single nerve, such as the median nerve in carpal tunnel syndrome.
• Myelin: the insulating coat around many nerve fibers that speeds up signals.
• Methylmalonic acid (MMA): a substance that builds up in the blood when cells lack vitamin B12.
• Monoclonal protein (M-protein): an antibody made in excess by one clone of plasma cells, found by protein electrophoresis and immunofixation.
• Nerve conduction study: a test that measures the speed and strength of electrical signals along nerves.

Frequently asked questions

How many people have neuropathy?

Studies estimate that 1% to 7% of the general population has peripheral neuropathy, and about 6% of adults aged 50 and over. Up to half of people with diabetes have it, often without symptoms.

What is the most common cause of peripheral neuropathy?

Diabetes is the leading cause in the US. Others include vitamin B12 deficiency, alcohol, chemotherapy, kidney disease, hypothyroidism and blood protein disorders; in 25% to 46% of cases, no cause is found.

Which blood tests are used for neuropathy?

Usually fasting glucose or HbA1c, vitamin B12, TSH, a complete blood count, kidney and liver tests, and serum protein electrophoresis with immunofixation. The AAN considers glucose, B12 with MMA and immunofixation the highest-yield tests.

Can neuropathy be reversed?

Sometimes. When the cause is found and corrected early, for example B12 deficiency, hypothyroidism, an offending medicine or an immune neuropathy, nerves can recover and regrow. In diabetes, glucose control aims to prevent or slow the damage, and NIDDK notes that pain medicines ease symptoms but do not reverse nerve damage.

What are the treatment options for numbness caused by peripheral neuropathy?

Numbness responds to treating the cause rather than to pain medicines. Physical therapy, braces or orthopedic shoes, daily foot checks and fall prevention reduce its consequences.

How does neuropathy affect sleep?

Nerve pain is often worse at night, and even bedsheets can hurt. Restless legs syndrome affects about one in five people with neuropathy. A bed cradle keeps covers off the feet, and the AAN asks doctors to treat sleep and mood problems along with the pain.

What diet is recommended for neuropathy in the feet?

A diet that keeps blood sugar, weight and lipids in range, with enough vitamin B12 and little or no alcohol. Plant-based, low-fat eating reduced pain modestly in a small pilot trial. Avoid high-dose vitamin B6 supplements, which can themselves cause neuropathy.

Is walking good for neuropathy?

Yes, for most people. Regular walking and other exercise improve balance, strength and sometimes pain. Wear protective shoes and check your feet after walking.

Sources

• England JD et al. — Practice Parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing — Neurology, 2009 — doi.org
• Castelli G, Desai KM, Cantone RE — Peripheral Neuropathy: Evaluation and Differential Diagnosis — Am Fam Physician, 2020 — pubmed.ncbi.nlm.nih.gov
• Huijg M et al. — Age- and Sex-Specific Prevalence and Incidence of Chronic Axonal Polyneuropathy in the General Population — Neuroepidemiology, 2026 — pubmed.ncbi.nlm.nih.gov
• American Diabetes Association Professional Practice Committee — 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes-2026 — Diabetes Care, 2026 — doi.org
• Price R et al. — Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary — Neurology, 2022 — doi.org
• Tesfaye S et al. — Amitriptyline, pregabalin and duloxetine combinations for diabetic peripheral neuropathic pain (OPTION-DM) — Lancet, 2022 — doi.org
• Callaghan BC et al. — Association Between Metabolic Syndrome Components and Polyneuropathy in an Obese Population — JAMA Neurol, 2016 — doi.org
• Yang W et al. — Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis — J Diabetes, 2019 — doi.org
• Seretny M et al. — Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis — Pain, 2014 — doi.org
• Loprinzi CL et al. — Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update — J Clin Oncol, 2020 — doi.org
• Jiménez-Jiménez FJ et al. — Association between restless legs syndrome and peripheral neuropathy: A systematic review and meta-analysis — Eur J Neurol, 2021 — doi.org
• Bunner AE et al. — A dietary intervention for chronic diabetic neuropathy pain: a randomized controlled pilot study — Nutr Diabetes, 2015 — doi.org
• Ma R et al. — Exercise training and balance function in middle-aged and older adults with diabetic peripheral neuropathy: a GRADE-based systematic review and meta-analysis — Front Public Health, 2026 — doi.org
• Rajasingham R, Qi Y — Suzetrigine, a Non-Opioid Small-Molecule Analgesic: Mechanism of Action, Clinical, and Translational Science — Clin Transl Sci, 2025 — doi.org
• Vertex Pharmaceuticals — Phase 3 study of suzetrigine in pain associated with diabetic peripheral neuropathy (placebo- and pregabalin-controlled) — ClinicalTrials.gov, NCT06628908 — clinicaltrials.gov
• Vertex Pharmaceuticals — Phase 3 placebo-controlled study of suzetrigine in pain associated with diabetic peripheral neuropathy — ClinicalTrials.gov, NCT07231419 — clinicaltrials.gov
• National Institute of Neurological Disorders and Stroke — Peripheral Neuropathy — NINDS — ninds.nih.gov
• National Institute of Neurological Disorders and Stroke — Guillain-Barré Syndrome — NINDS — ninds.nih.gov
• NIDDK — Peripheral Neuropathy (diabetic nerve damage) — National Institutes of Health — niddk.nih.gov
• MedlinePlus — Peripheral Nerve Disorders — National Library of Medicine — medlineplus.gov
• MedlinePlus — Peripheral neuropathy — Medical Encyclopedia — medlineplus.gov
• MedlinePlus — Methylmalonic Acid (MMA) Test — National Library of Medicine — medlineplus.gov
• MedlinePlus — Vitamin B12 level, TSH test, A1C test, Blood sugar test, Creatinine blood test — Medical Encyclopedia — medlineplus.gov
• MedlinePlus — Protein electrophoresis - serum and Immunoelectrophoresis - blood — Medical Encyclopedia — medlineplus.gov

Further reading

• Neuralgia: nerve pain symptoms and treatment
• Numbness in the heel: causes, tests and treatment
• Diabetes blood test: glucose, HbA1c and insulin
• Vitamin panel blood test: D, B12 and folate
• Diabetic toenails: symptoms, causes and care
• Folate deficiency: symptoms, causes and the B12 link

Understand your lab results with AI DiagMe

A neuropathy workup often brings a long list of results: glucose and HbA1c, vitamin B12 and methylmalonic acid, TSH, kidney and liver tests, a blood count and a protein electrophoresis. AI DiagMe reads your lab report in minutes, explains each result in plain language, shows which values may explain your symptoms and suggests questions to ask your doctor. Upload your lab results to AI DiagMe for a clear, personal report.