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Neurology

Peripheral Neuropathy

Peripheral neuropathy is dysfunction of one or more peripheral nerves; the common chronic form is a length-dependent distal polyneuropathy, but focal, multifocal, autonomic, demyelinating and acute patterns require different investigation and urgency.

In a nutshell

Peripheral neuropathy is a pattern, not a single disease. Chronic length-dependent distal polyneuropathy commonly causes sensory loss or pain in the feet, but focal, multifocal, autonomic, motor-predominant, demyelinating and rapidly progressive patterns need different investigation. Identify and treat the cause, protect insensate feet, use NICE neuropathic-pain options safely and escalate red flags urgently.

Classic presentation

A person develops persistent burning or numb feet with reduced ankle reflexes and impaired vibration in a symmetrical distal pattern. Ask about diabetes, alcohol, medicines, B12 risk, systemic symptoms and progression, then examine the feet and look for cord, root, motor or autonomic signs.

Key points

  • Describe distribution, fibre type, symmetry and tempo before deciding that symptoms represent a chronic polyneuropathy.
  • For persistent distal altered sensation with depressed reflexes, consider B12, thyroid, coeliac, renal, glucose, ESR and alcohol causes; add targeted tests for the phenotype.
  • Neurophysiology supports classification and detects treatable mimics, but it does not independently diagnose neuropathy and can be normal in small-fibre disease.
  • Rapid ascending weakness, bulbar or respiratory symptoms, autonomic instability, a sensory level or upper motor neurone signs require urgent assessment.
  • Diabetic foot risk assessment includes monofilament testing, vascular assessment, inspection and risk stratification; pain may be absent in serious foot disease.
  • A red, hot, swollen or deformed foot with neuropathy may be acute Charcot arthropathy and needs urgent specialist referral and offloading.
  • NICE first-line neuropathic-pain choices are amitriptyline, duloxetine, gabapentin or pregabalin; review benefit, function, adverse effects and the need to continue.
  • Gabapentinoids require current MHRA counselling about dependence and withdrawal, and caution with respiratory disease, renal impairment, older age, opioids, alcohol or other CNS depressants.
  • Treat the cause and rehabilitate balance, mobility, autonomic symptoms and skin protection rather than treating pain alone.

First-line investigation

Pattern-focused neurological and foot examination with targeted blood tests for common and reversible causes; arrange specialist neurophysiology or urgent testing when the pattern is atypical or rapidly progressive.

Management

Localise and investigate the cause

  • Use the distribution, fibre signs, reflexes, tempo and systemic context to choose targeted blood tests and specialist investigation; escalate acute, motor, asymmetric or central red flags.1,2

Treat the cause and neuropathic pain

  • Treat reversible causes and offer amitriptyline, duloxetine, gabapentin or pregabalin for neuropathic pain, with review and switching if ineffective or not tolerated.4,5

Protect feet and preserve function

  • Perform diabetic foot-risk assessment, provide skin and footwear advice, refer a suspected Charcot foot urgently for offloading, and use rehabilitation for balance, mobility, foot drop and falls.6,2

Escalate atypical or emergency patterns

  • Rapid ascending weakness, bulbar or respiratory compromise, autonomic instability, painful asymmetric deficits, proximal weakness, demyelinating features or cord signs need urgent specialist assessment.1,2

Review safety and treatment burden

  • Review pain, sleep, function, falls, skin integrity, autonomic symptoms, treatment benefit, sedation, renal safety, dependence and withdrawal risk, and reassess the diagnosis if the trajectory changes.4,7,8,5

Exam traps

  • A stocking distribution does not prove diabetes; check reversible and systemic causes.
  • A sensory level, brisk reflexes or sphincter symptoms suggest spinal cord disease rather than uncomplicated peripheral neuropathy.
  • Rapid ascending weakness is an emergency pattern, not routine diabetic neuropathy.
  • A painless red, hot, swollen diabetic foot can still be acute Charcot arthropathy or serious infection.
  • Nerve-conduction studies can be normal in small-fibre neuropathy and are not a substitute for clinical examination.
  • Do not use long-term tramadol or other strong opioids as routine first-line treatment for chronic neuropathic pain.
  • Gabapentin and pregabalin are not risk-free: consider dependence, withdrawal, sedation, renal clearance and respiratory depression.

Illustrations

10 g monofilament testing for distal sensory neuropathyA 10 g monofilament is applied to the foot to test protective sensation, which may be reduced distally in diabetic or other length-dependent peripheral neuropathy. Show the testing sites and explain that this is part of a wider foot and vascular assessment.Swain J et al., Cureus 2023, CC-BY-3.0 · CC-BY-3.0

Key sources

  1. NICE NG127, Suspected neurological conditions: recognition and referral (Current NICE adult recommendations: persistent distally predominant altered sensation with depressed reflexes should prompt consideration of peripheral neuropathy and checks for B12 deficiency, thyroid disease, coeliac disease, renal function, blood glucose, ESR and alcohol; refer when no cause is found or features are atypical)Updated 26 Jul 2019
  2. NHS, Peripheral neuropathy: symptoms, causes, diagnosis and treatment (NHS condition information on sensory, motor, autonomic and mononeuropathy patterns, common causes, blood tests, neurophysiology, pain treatment and functional support; page last reviewed 2022 and used as supplementary patient-facing context)Updated 10 Oct 2022
  3. University Hospitals Birmingham NHS Foundation Trust, Peripheral neuropathy pathway (UK NHS neurology referral pathway last reviewed 26 January 2026: practical baseline investigations for diabetes or glucose intolerance, B12, paraprotein, liver disease and functional status; used as local pathway context, not as a universal national protocol)Updated 26 Jan 2026
  4. NICE CG173, Neuropathic pain in adults: pharmacological management in non-specialist settings (Current NICE pharmacological pathway: offer a choice of amitriptyline, duloxetine, gabapentin or pregabalin; switch when ineffective or not tolerated; consider tramadol only for acute rescue and capsaicin cream for localised pain; avoid routine long-term opioids in non-specialist settings)Updated 8 Sept 2020
  5. BNF, current prescribing information for neuropathic-pain medicines (Current UK prescribing source for dosing, renal adjustment, contraindications, interactions, controlled-drug requirements, monitoring and withdrawal; direct access was restricted and the available browser session was unavailable, so unsupported doses were omitted)
  6. NICE NG19, Diabetic foot problems: prevention and management (NICE diabetic-foot guidance last updated 2019 with risk-assessment recommendations reviewed 2023 and exceptional surveillance evidence available in 2025: annual and event-triggered foot assessment, 10 g monofilament, risk stratification, urgent Charcot referral, offloading and infection or ischaemia escalation)Updated 1 Sept 2024
  7. MHRA, Improving information supplied with gabapentinoids, benzodiazepines and z-drugs (MHRA update published 8 January 2026: gabapentin and pregabalin carry risks of addiction, dependence, tolerance and withdrawal; discuss a reduction or stopping plan before treatment and taper gradually when appropriate)Updated 8 Jan 2026
  8. MHRA, Pregabalin: reports of severe respiratory depression (MHRA Drug Safety Update published 18 February 2021: consider respiratory-depression risk and dose or regimen adjustment in respiratory or neurological disease, renal impairment, older age or concomitant CNS depressants)Updated 18 Feb 2021

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.