Peripheral neuropathy
Peripheral neuropathy is damage to the peripheral nerves, the network that carries signals between the brain and spinal cord and the rest of the body. It commonly causes numbness, tingling, pain and weakness, usually starting in the feet. Diabetes is the most common cause, but there are more than 100 types with many different causes1,2.
This information is for education. It is not medical advice and does not replace assessment by a qualified health professional. Anyone concerned about symptoms should consult a doctor; in an emergency, local emergency services should be contacted.
What it is
The peripheral nervous system is made up of nerves outside the brain and spinal cord1. Sensory nerves carry information such as touch, temperature and pain; motor nerves control muscles; and autonomic nerves regulate automatic functions such as heart rate, blood pressure, digestion and sweating1,2.
Peripheral neuropathy means damage to these nerves. Some forms affect a single nerve or a few nerves, but most affect many nerves at once (polyneuropathy)1. The most common pattern is distal symmetric polyneuropathy, in which symptoms begin in both feet and may later spread up the legs and to the hands, because the longest nerve fibres are affected first1,3.
Neuropathy becomes more common with age; population studies suggest that about 1% of the general population and up to 7% of older people have polyneuropathy4. It can lead to pain, falls, foot ulcers and amputations3.
Signs and symptoms
Symptoms depend on which types of nerve are affected, and may develop over days, weeks or years1. Neuropathic pain, pain caused by damage to the nerves themselves, is often worse at night1.
- Numbness and tingling, often starting in the feet or hands1,2
- Burning, stabbing or shooting pain, sometimes pain from a light touch such as bedsheets (allodynia)1,2
- Loss of balance and co-ordination, especially in the dark or with the eyes closed, because of reduced position sense1,2
- Muscle weakness, cramps, twitching or muscle wasting when motor nerves are involved1
- Reduced ability to feel pain or temperature, which raises the risk of foot injuries and ulcers1,2
- Autonomic symptoms such as too much or too little sweating, problems regulating blood pressure, and digestive problems1,2
Causes and risk factors
Neuropathy can be acquired during life or inherited, and in about 20-30% of cases no cause is found (idiopathic neuropathy)1,4. In Western countries, diabetes, alcohol overuse, chemotherapy drugs and cardiovascular disease are the factors most commonly associated with polyneuropathy, whereas infections such as leprosy are more common causes in some developing countries4.
- Diabetes: the most common cause in the United Kingdom and the United States; long-term high blood sugar damages the nerves, and the metabolic syndrome (a cluster including obesity, high blood pressure and abnormal blood fats) is a major additional risk factor1,2,6
- Alcohol overuse and vitamin problems, particularly vitamin B12 deficiency or excess vitamin B61
- Medicines, especially some chemotherapy drugs, as well as certain treatments for HIV, infections and seizures1
- Infections such as shingles (varicella zoster), HIV, Lyme disease and leprosy1,4
- Autoimmune conditions in which the immune system attacks the nerves, such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP)1
- Kidney or liver disease, hormonal disorders and some cancers1
- Physical injury or pressure on a nerve, as in carpal tunnel syndrome1
- Inherited neuropathies, such as Charcot-Marie-Tooth disease1,10
Genetics
Most peripheral neuropathy is acquired, and a genetic cause is uncommon1. Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy and includes a large group of conditions caused by variants in many different genes10,11.
The most common type, CMT1A, is caused by a duplication of the PMP22 gene, which leads to too much of a protein needed for myelin, the insulating sheath around nerve fibres; deletion of one copy of the same gene causes hereditary neuropathy with liability to pressure palsies10. Variants in MPZ cause CMT1B, and the X-linked form CMTX is the second most common type10.
Next-generation sequencing, which reads many genes or whole genomes at once, is changing how CMT is diagnosed, although deciding whether a rare variant is truly harmful can be difficult11.
What happens in the nerves
In peripheral neuropathy the damage lies mainly outside the brain and spinal cord, in the peripheral nerves. It can affect the axon, the long fibre that carries the nerve signal, or the myelin sheath that insulates it1. When nerves are damaged, signals may fail to arrive, may be sent when they should not be, or may be distorted1.
In diabetic neuropathy, nerve function is lost progressively from the farthest points of the nerves towards the body6. The mechanisms are complex but converge on bioenergetic failure, a breakdown of energy supply and use within peripheral nerves, which are especially vulnerable because of their great length6. The exact mechanisms in type 1 and type 2 diabetes are still not fully understood5.
Pain arises when damaged pain-sensing fibres fire spontaneously or when signal processing in the spinal cord changes so that normally harmless touch is felt as painful1. In autoimmune neuropathies, antibodies and immune cells attack the nerves or their myelin1.
How it is diagnosed
Diagnosis starts with a detailed history of symptoms, medicines, alcohol use, toxin exposure and family history, together with a neurological examination of sensation, strength and reflexes1. For people with typical symptoms and no known cause, a limited set of blood tests, including glucose, vitamin B12 and blood proteins, is recommended3.
Atypical features, such as one-sided symptoms, rapid onset, weakness more than sensory loss or prominent autonomic problems, should prompt referral to a neurologist3. People at high risk, such as those with diabetes, are advised to have regular checks2.
- Blood tests for diabetes, vitamin deficiencies, kidney and liver function and abnormal immune activity1,3
- Nerve conduction studies, which measure how fast and how strongly signals travel along nerves, and electromyography (EMG), which records the electrical activity of muscles1
- Skin biopsy to count small nerve fibres, used for small-fibre neuropathy that standard nerve tests can miss1
- Autonomic tests, such as measuring sweat production1
- Genetic testing when an inherited neuropathy is suspected1,11
- MRI or nerve ultrasound in selected cases, for example to look for nerve compression1
How scientists study it
Door-to-door surveys, cohort studies and health-record studies estimate how common polyneuropathy is and which risk factors are linked to it4.
Nerve conduction studies and EMG distinguish damage to axons from damage to myelin and are used to measure nerve function in research and practice1,3.
Counting nerve fibre endings in small skin samples and measuring sweating allow researchers to study small-fibre neuropathies1.
Gene panels, whole-exome and whole-genome sequencing are used to identify the genetic causes of CMT and related disorders11.
Laboratory studies of how peripheral nerves produce and use energy aim to identify molecular mechanisms that could become treatment targets6.
Large trials compare treatments for neuropathic pain, such as the OPTION-DM trial of amitriptyline, duloxetine and pregabalin in painful diabetic neuropathy8.
Meta-analyses of hundreds of trials rank medicines for neuropathic pain by effectiveness, safety and quality of evidence7.
Current treatments
Treatment depends on the cause, and some neuropathies improve when it is corrected1,2. Not every cause can be treated, and in some people the damage is permanent2.
Good glucose control greatly reduces the development of neuropathy in type 1 diabetes, but has a more modest effect in type 2 diabetes, in which managing the metabolic syndrome is also important3,5,6.
Ordinary painkillers often do not work for nerve pain2. Tricyclic antidepressants such as amitriptyline, serotonin-noradrenaline reuptake inhibitors such as duloxetine, and pregabalin and gabapentin are recommended first-line options, while opioids are discouraged5,7. In the United Kingdom, NICE guidance covers the choice of these medicines in non-specialist settings9.
In the OPTION-DM trial, amitriptyline, duloxetine and pregabalin worked similarly well for painful diabetic neuropathy, and combining two of them helped people whose pain did not respond well to one8.
Neuropathies caused by the immune system may be treated with intravenous immunoglobulin, steroids, other immunosuppressants or plasma exchange (plasmapheresis), in which antibodies are removed from the blood1.
Physiotherapy, braces, splints, orthopaedic footwear and walking aids help with weakness and balance, and surgery may relieve pressure on a compressed nerve1,2. There is no cure for CMT, but therapy and supportive devices help people stay mobile10.
Stopping smoking, avoiding excess alcohol, exercising, eating healthily and maintaining a healthy weight support nerve health1.
Research frontiers
Current medicines treat symptoms rather than nerve damage, and new treatments that prevent or reverse neuropathy are needed, especially in type 2 diabetes3.
Researchers are testing whether diet, exercise and treatment of the metabolic syndrome can prevent or slow diabetic neuropathy6.
New approaches aim to detect diabetic neuropathy earlier and predict who will progress6.
Whole-genome sequencing is being incorporated into diagnostic pathways for CMT to improve the rate of genetic diagnosis11.
Head-to-head trials are clarifying which first-line medicines and combinations work best for individuals8.
Living with the condition and seeking help
It is worth seeing a doctor about pain, tingling or loss of feeling in the feet, weakness or loss of balance, or a cut or ulcer on the foot that is not healing2. The sooner neuropathy is diagnosed, the better the chance of limiting the damage and preventing complications2.
Tingling followed by weakness that spreads and worsens over days to weeks can be a sign of Guillain-Barré syndrome, a rare but serious condition that needs urgent hospital treatment, and urgent medical advice should be sought if it is suspected12. Drooping of the face, trouble swallowing or speaking, or being unable to lift one or both arms need emergency care straight away12. In India, the national emergency number is 112 and the ambulance number is 10813,14.
Untreated foot problems, such as an ulcer that becomes infected, can lead to gangrene and in severe cases amputation, so injuries to numb feet should be checked promptly2. People at higher risk, such as those with diabetes, are advised to have regular check-ups of nerve function2.
References
- National Institute of Neurological Disorders and Stroke, United States. Peripheral neuropathy. Link
- NHS (United Kingdom). Peripheral neuropathy. Link
- Callaghan BC, Price RS, Feldman EL. Distal symmetric polyneuropathy: a review. JAMA. 2015;314:2172-2181. doi:10.1001/jama.2015.13611 · PubMed
- Hanewinckel R, van Oijen M, Ikram MA, van Doorn PA. The epidemiology and risk factors of chronic polyneuropathy. Eur J Epidemiol. 2016;31:5-20. doi:10.1007/s10654-015-0094-6 · PubMed
- Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5:41. doi:10.1038/s41572-019-0092-1 · PubMed
- Elafros MA, Andersen H, Bennett DL, et al. Towards prevention of diabetic peripheral neuropathy: clinical presentation, pathogenesis, and new treatments. Lancet Neurol. 2022;21:922-936. doi:10.1016/S1474-4422(22)00188-0 · PubMed
- Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:162-173. doi:10.1016/S1474-4422(14)70251-0 · PubMed
- Tesfaye S, Sloan G, Petrie J, et al. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial. Lancet. 2022;400:680-690. doi:10.1016/S0140-6736(22)01472-6 · PubMed
- National Institute for Health and Care Excellence (NICE), United Kingdom. Neuropathic pain in adults: pharmacological management in non-specialist settings. Clinical guideline CG173. 2013 (updated 2020). Link
- National Institute of Neurological Disorders and Stroke, United States. Charcot-Marie-Tooth disease. Link
- Pipis M, Rossor AM, Laura M, Reilly MM. Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges. Nat Rev Neurol. 2019;15:644-656. doi:10.1038/s41582-019-0254-5 · PubMed
- NHS (United Kingdom). Guillain-Barré syndrome. Link
- Press Information Bureau, Government of India (Ministry of Women and Child Development). Panic button becomes available to women with launch of ERSS and pan-India emergency number 112. 19 February 2019. Link
- National Health Mission, Ministry of Health and Family Welfare, Government of India. ERS/Patient Transport Service: National Ambulance Service (Dial 108/102). Accessed October 2026. Link
Prepared 15 October 2026.
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