Peripheral neuropathy is damage to the nerves outside the brain and spinal cord. It most often affects the feet and hands symmetrically, causing tingling, burning, numbness, pain, weakness or loss of balance, and sometimes affects the nerves controlling blood pressure, digestion and bladder. Diabetes is the commonest cause; others include vitamin B12 deficiency, alcohol, chemotherapy, kidney disease, thyroid disease, autoimmune conditions, infections, inherited disorders and some medications, and in about a quarter of cases no cause is found. Treatment means correcting the cause where possible, specific medications for nerve pain, and protecting numb feet from injury.
What peripheral neuropathy is
The peripheral nervous system is everything outside the brain and spinal cord: the nerves running to the skin, muscles and organs. Peripheral neuropathy means these nerves are damaged. When many nerves are affected together, symmetrically, it is called polyneuropathy; when a single nerve is affected, mononeuropathy (carpal tunnel syndrome is the commonest); when several separate nerves are hit, mononeuritis multiplex.
Nerves contain three kinds of fibre, and neuropathy can affect any combination:
- Sensory fibres — large ones carry touch, vibration and position sense; small ones carry pain and temperature.
- Motor fibres — control muscle.
- Autonomic fibres — regulate heart rate, blood pressure, sweating, digestion, bladder and sexual function.
Most polyneuropathies are "length-dependent": the longest fibres, running to the toes, fail first, and damage spreads upward in a stocking pattern before reaching the hands.
Symptoms
Sensory
- tingling, pins and needles, buzzing
- burning, stabbing, electric or shooting pain
- heightened sensitivity — bedsheets or socks feel painful (allodynia)
- numbness, or a feeling of walking on cotton wool or thick socks
- inability to feel temperature or injury
- loss of position sense, causing unsteadiness, especially in the dark
Motor
- weakness, usually starting in the feet (difficulty lifting the toes or foot — "foot drop")
- muscle cramps and twitching
- muscle wasting in advanced cases
Autonomic
- dizziness on standing
- abnormal sweating — too little in the feet, too much elsewhere
- bloating, nausea, constipation or diarrhoea
- difficulty emptying the bladder
- erectile dysfunction
- heat intolerance
Small-fibre neuropathy causes burning pain and abnormal temperature sensation with normal strength and reflexes, and is easily missed on standard tests. See tingling in the hands and feet for how to interpret the early symptoms.
Causes
More than a hundred are recognized. The important groups:
Metabolic - Diabetes — the commonest cause in developed countries, accounting for around a third of cases - Prediabetes and metabolic syndrome — increasingly recognized as causes of small-fibre neuropathy - Chronic kidney disease - Hypothyroidism
Nutritional - Vitamin B12 deficiency — common, especially with long-term metformin, acid-suppressing drugs, vegan diets and in older adults - Thiamine (B1) deficiency, usually with alcohol - Vitamin B6 — both deficiency and, paradoxically, excess from high-dose supplements - Copper deficiency, often after bariatric surgery or from excess zinc - Vitamin E deficiency
Toxic - Alcohol — the second commonest cause overall - Chemotherapy (platinum drugs, taxanes, vinca alkaloids, bortezomib) - Other medications: some antibiotics (metronidazole, nitrofurantoin, fluoroquinolones), amiodarone, some HIV drugs, phenytoin - Heavy metals (lead, arsenic), industrial solvents
Inflammatory and autoimmune - Guillain-Barré syndrome (acute) and CIDP (chronic) - Vasculitis - Sjögren's syndrome, lupus, rheumatoid arthritis, coeliac disease - Paraproteinaemias (abnormal antibodies from plasma cells)
Infectious - HIV, hepatitis C, Lyme disease, leprosy (globally the commonest infectious cause), shingles (post-herpetic neuralgia)
Inherited - Charcot-Marie-Tooth disease and related disorders
Compressive - Carpal tunnel, ulnar nerve at the elbow, peroneal nerve at the knee
Idiopathic — in about 20–30% of cases, particularly in older people, no cause is found despite full investigation.
How doctors diagnose it
- History — timing, pattern, symmetry, alcohol, medications, diet, family history, occupation.
- Examination — sensation to light touch, pinprick, vibration and position; reflexes; strength; gait; foot inspection; lying and standing blood pressure.
- Blood tests — the standard screen is glucose or A1C, vitamin B12 (with methylmalonic acid if borderline), thyroid function, kidney and liver function, full blood count, and serum protein electrophoresis for paraproteins. Further tests depend on the picture: B1, B6, copper, HIV, hepatitis, coeliac antibodies, autoimmune markers, genetic testing.
- Nerve conduction studies and electromyography — measure how fast and how well nerves and muscles conduct signals; distinguish damage to the nerve's insulation (demyelination) from damage to the fibre itself (axonal), which points to different causes. Normal in small-fibre neuropathy.
- Skin biopsy to count small nerve fibres, for suspected small-fibre neuropathy.
- Autonomic testing where autonomic symptoms are prominent.
- Nerve biopsy, imaging or lumbar puncture in selected cases.
Treatment
Treat the cause
This is the intervention with the largest effect, and the reason diagnosis matters. Correcting B12 or thiamine deficiency, stopping alcohol or a causative drug, treating hypothyroidism, controlling glucose, or immunotherapy for inflammatory neuropathies can halt progression and, if started early, allow recovery.
Treat the pain
Neuropathic pain does not respond to paracetamol or ibuprofen. First-line medications with good trial evidence:
- Duloxetine or venlafaxine (SNRIs)
- Pregabalin or gabapentin
- Amitriptyline or nortriptyline (tricyclics), effective but with more side effects in older adults
Second-line and topical options: capsaicin cream or 8% patches, lidocaine patches, tramadol. Opioids are avoided where possible. Combinations are used when single agents are insufficient.
Protect and rehabilitate
- Daily foot inspection, protective footwear, prompt attention to wounds, and podiatry for anyone with reduced foot sensation
- Physiotherapy and balance training, which reduce falls
- Ankle-foot orthoses for foot drop
- Occupational therapy for hand function
- Management of dizziness (compression stockings, fluids, medication) and digestive and bladder symptoms
Supplements
Alpha-lipoic acid has modest trial evidence for symptoms of diabetic neuropathy. Benfotiamine has weaker evidence. B vitamins are useful only when deficient — and high-dose B6 causes neuropathy. None repairs nerves. Any supplement should be discussed with the doctor managing the neuropathy, since some interact with medication and some (B12 in particular) can mask a diagnosis if started before testing.
When to contact a doctor
See a doctor for tingling, numbness, burning or weakness that persists more than a couple of weeks, is spreading, or affects balance. Seek urgent care for rapidly progressive weakness over hours or days, weakness that ascends from the legs, difficulty breathing or swallowing, or neuropathy with severe dizziness or fainting — Guillain-Barré syndrome and some other acute neuropathies are emergencies. For a foot that is red, hot, swollen or has a non-healing wound, same-day assessment.
Frequently asked questions
Can peripheral neuropathy be cured?
It depends on the cause. Neuropathy from B12 deficiency, thyroid disease, a medication or alcohol can improve substantially, sometimes completely, once the cause is corrected early. Nerve damage from long-standing diabetes or from inherited disorders usually cannot be undone, though progression can be slowed and symptoms treated.
What is the difference between neuropathy and neuralgia?
Neuropathy is damage to a nerve or nerves. Neuralgia is pain in the distribution of a nerve, which may or may not involve damage — trigeminal neuralgia in the face is the classic example.
Why does it get worse at night?
Several reasons: fewer distractions, the pressure of bedclothes on hypersensitive skin, cooler temperature, and the natural daily rhythm of pain perception. Night-time worsening is typical of neuropathic pain generally.
Should I see a neurologist?
Typical, slowly progressive, symmetrical foot-first neuropathy with a known cause such as diabetes can be managed in primary care. Rapid onset, asymmetry, prominent weakness, onset in the hands, or no cause found on initial tests all warrant a neurologist.
References
- National Institute of Neurological Disorders and Stroke. Peripheral Neuropathy (2024). https://www.ninds.nih.gov/health-information/disorders/peripheral-neuropathy
- NIDDK. Diabetic Neuropathy (2023). https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/nerve-damage-diabetic-neuropathies
- NIH Office of Dietary Supplements. Vitamin B12 — Fact Sheet for Health Professionals (2024). https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
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