Peripheral neuropathy: assessment and management in Australian general practice

Peripheral neuropathy is damage to the peripheral nervous system — the nerves connecting the brain and spinal cord to the rest of the body — producing sensory, motor, and autonomic symptoms. In Australian general practice, peripheral neuropathy is a daily clinical encounter: the patient with a decade of type 2 diabetes and numb soles, the person on long-term metformin with a low-normal B12, the older patient with new balance problems and unexplained sensory loss.

Diabetes mellitus is the leading cause in Australia, accounting for roughly half of all peripheral neuropathy cases. Alcohol-related nerve damage and nutritional deficiencies (B12, thiamine) are next in frequency. The clinical discipline is to exclude treatable and reversible causes before accepting a diagnosis of idiopathic neuropathy — because reversible causes are missed at significant patient cost, and some presentations (Guillain-Barré syndrome, vasculitic neuropathy, acute spinal cord compression) are emergencies.

Peripheral neuropathy is classified by anatomy (mononeuropathy, mononeuritis multiplex, or polyneuropathy), by predominant fibre type (large-fibre or small-fibre), by pathology (axonal or demyelinating on nerve conduction studies), and by course (acute, subacute, or chronic). Management follows from this classification: treat the underlying cause where possible, control neuropathic pain with guideline-concordant pharmacotherapy, and protect the feet in diabetes.

A. Core clinical — the AU general-practice framework

Causes: the DANG THE RAPIST mnemonic

The broad aetiology of peripheral neuropathy covers many categories. A practical mnemonic used in RACGP training is DANG THE RAPIST:

• Diabetes — T1DM and T2DM; correlates with duration and glycaemic control; leading cause in Australia.
• Alcohol — direct neurotoxicity plus nutritional deficiencies (B1/thiamine, B12).
• Nutritional — B12 (pernicious anaemia, gastrectomy, metformin long-term, vegan diet, atrophic gastritis); thiamine (alcohol, malabsorption); folate; copper (gastric bypass, excess zinc); vitamin E (fat malabsorption).
• Guillain-Barré / CIDP — acute or chronic inflammatory demyelinating neuropathy; immune-mediated; GBS is a medical emergency.
• Toxic / drug-induced — chemotherapy agents (vincristine, cisplatin, oxaliplatin, taxanes, bortezomib), prolonged metronidazole or nitrofurantoin, isoniazid (co-prescribe pyridoxine), amiodarone, older antiretrovirals, heavy metals, organophosphates.
• Hereditary — Charcot-Marie-Tooth disease (CMT); hereditary neuropathy with liability to pressure palsies (HNPP).
• Endocrine — hypothyroidism, acromegaly.
• Recurrent inflammatory / vasculitic — CIDP, vasculitis (PAN, EGPA, GPA), sarcoidosis, Sjögren’s, RA, SLE.
• Amyloid — primary AL, hereditary TTR, secondary AA; typically small-fibre and autonomic features.
• Paraneoplastic — anti-Hu antibody (small-cell lung); subacute sensory neuronopathy; consider when rapid onset in an older patient.
• Infectious — HIV, hepatitis C, syphilis, COVID-19 post-acute sequelae; leprosy is rare but imported in Australia.
• Structural / compression — carpal tunnel (median nerve), cubital tunnel (ulnar), peroneal nerve at the fibular head, meralgia paraesthetica.
• Trauma — surgical, accidental nerve injury.
• Renal failure — uraemic neuropathy; improves with dialysis or transplant.

History

A structured history drives both diagnosis and management:

• Onset and course — acute (days to weeks): consider GBS; subacute (4–8 weeks): CIDP, vasculitic, paraneoplastic; chronic (months to years): diabetic, alcoholic, hereditary, idiopathic.
• Symptom type — sensory (numbness, tingling, burning, allodynia); motor (weakness, foot drop, falls); autonomic (orthostatic dizziness, gastroparesis, erectile dysfunction, gustatory sweating, bladder dysfunction).
• Distribution — distal symmetric glove-and-stocking polyneuropathy vs focal (mononeuropathy: carpal tunnel, ulnar elbow, peroneal).
• Diabetes history — duration, HbA1c trend, insulin or oral agents, prior foot problems or ulceration.
• Alcohol — weekly consumption; nutritional adequacy.
• Medications — metformin (B12 depletion), chemotherapy, prolonged metronidazole or nitrofurantoin, isoniazid, amiodarone, statins.
• Nutritional status — vegan or strict vegetarian diet, malabsorption (coeliac disease, bariatric surgery, gastrectomy).
• Family history — CMT, HNPP; foot deformities in relatives.
• Systemic symptoms — weight loss, joint pains, dry eyes and mouth, rash.

Physical examination

The RACGP Diabetes Clinical Audit and eTG Neurology both recommend structured neurological assessment:

• 10g Semmes-Weinstein monofilament — essential diabetic foot screening; applied to 10 plantar sites; ≥4 missed sites indicates significant loss of protective sensation and increased ulceration risk.
• 128 Hz tuning fork — vibration sense at the great toe, medial malleolus, tibial crest; large-fibre test; compare bilaterally.
• Proprioception — big-toe position sense; Romberg test for falls risk.
• Pinprick and light touch — small-fibre assessment in the glove-and-stocking distribution.
• Reflexes — ankle jerk (lost early in peripheral polyneuropathy), knee jerk.
• Motor power — foot dorsiflexion (peroneal/L4–5 level), intrinsic hand muscles, grip strength.
• Gait and balance — steppage gait (foot drop), Romberg-positive ataxia.
• Skin — foot ulcers, callus, nail changes, Charcot deformity, anhidrosis.
• Postural BP and pulse — autonomic neuropathy screen.

Investigation

Per Therapeutic Guidelines (eTG), a targeted blood workup is first-line for all patients with unexplained peripheral neuropathy:

Standard first-line bloods:

• Fasting glucose and HbA1c — screen for undiagnosed or poorly controlled diabetes
• Vitamin B12 and folate
• TSH — hypothyroidism causes a predominantly large-fibre neuropathy
• Serum creatinine, eGFR, LFT — renal and hepatic causes
• FBC — macrocytic anaemia may indicate B12 or folate deficiency
• ESR and CRP — inflammatory causes
• Serum protein electrophoresis (SPEP) and immunofixation — paraproteinaemia and myeloma, especially in patients over 50 with unexplained neuropathy

Selective additional testing:

• ANA, RF, ANCA, anti-Ro/La — if vasculitis or connective tissue disease is suspected
• HIV and hepatitis B/C serology — if risk factors are present
• Anti-neuronal antibodies — if paraneoplastic aetiology is considered

Specialist investigations:

• Nerve conduction studies (NCS) and EMG — distinguishes axonal from demyelinating neuropathy, localises lesions, and confirms the clinical diagnosis; ordered via neurologist referral and Medicare-rebatable through that pathway.
• Skin biopsy with intraepidermal nerve fibre density measurement — for small-fibre neuropathy where NCS may be normal.

B. Evidence appraisal — neuropathic pain pharmacotherapy

Neuropathic pain — burning, shooting, or lancinating pain arising from nerve damage — requires pharmacotherapy distinct from nociceptive pain management. Therapeutic Guidelines (eTG) and the landmark Finnerup et al. NeuPSIG systematic review and meta-analysis (Lancet Neurology 2015) identify four first-line oral agents.

First-line agents:

Agent	Usual dose range	PBS status	Key notes
Pregabalin	75–600 mg/day in 2 doses	Authority Required	SafeScript / real-time prescription monitoring (RTPM); start 75 mg twice daily and titrate over weeks
Gabapentin	300–3600 mg/day in 3 doses	Authority Required (after pregabalin failure)	Slower titration; similar efficacy and side-effect profile to pregabalin; SafeScript / RTPM
Duloxetine	30–120 mg/day	PBS Authority for diabetic peripheral neuropathic pain	SNRI; particularly effective in painful diabetic neuropathy; addresses comorbid depression or anxiety
Amitriptyline	10–75 mg nocte	PBS general schedule (off-label for neuropathic pain)	Tricyclic antidepressant; useful with comorbid insomnia or depression; caution in older adults — anticholinergic burden (confusion, urinary retention, falls, dry mouth, constipation, cardiac arrhythmia)

Topical agents for focal neuropathic pain (post-herpetic neuralgia, focal nerve compression):

• Capsaicin 0.075% cream — apply 3–4 times daily; initial burning side effect diminishes with continued use; available OTC.
• Lignocaine 5% patch — special access scheme in Australia; specialist context.

Opioids and neuropathic pain — the ANZCA position:

The Faculty of Pain Medicine at ANZCA is explicit: long-term opioids for chronic neuropathic pain produce limited benefit against significant harm — including opioid dependence, opioid-induced hyperalgesia, cognitive impairment, falls, and all-cause mortality. Opioids are not appropriate as first-, second-, or third-line treatment for chronic peripheral neuropathic pain. Tramadol has weak dual mechanisms (μ-opioid and serotonin–noradrenaline reuptake inhibition) and is sometimes used selectively, but carries dependence risk, serotonin syndrome in combination with SSRIs or SNRIs, and falls risk in older adults.

Carbamazepine exception: Carbamazepine is first-line specifically for trigeminal neuralgia per eTG — it is not appropriate for peripheral polyneuropathy.

Multimodal management: Pharmacotherapy is most effective integrated with:

• Aerobic and resistance exercise — reduces perceived pain and improves nerve function and mood
• Physiotherapy — gait and balance retraining, splinting, TENS as adjunct
• Psychological approaches — CBT, acceptance and commitment therapy (ACT), mindfulness for chronic pain adjustment
• Sleep management — pain and sleep have a bidirectional relationship; treating insomnia can meaningfully reduce pain perception
• Specialist pain medicine for refractory cases and spinal cord stimulator candidacy

C. Foot care and falls prevention in diabetic neuropathy

Diabetic peripheral neuropathy is the leading cause of lower-limb amputation in Australia. When peripheral neuropathy is combined with peripheral arterial disease and structural foot deformity, the amputation risk is substantially elevated. Diabetes Australia identifies daily foot care and multidisciplinary team involvement as the principal preventive tools.

Daily self-care for patients with diabetic neuropathy:

• Inspect all surfaces of the feet every day — use a handheld mirror for the sole.
• Wash feet in warm (not hot) water, testing temperature first with an elbow.
• Dry thoroughly between the toes — moisture promotes fungal infection and skin maceration.
• Apply emollient to heels and soles; avoid between the toes.
• Never walk barefoot, even indoors on soft surfaces.
• Wear well-fitting, closed-toe footwear with pressure-redistributing insoles.

General practice responsibilities:

• Monofilament test at every diabetes annual cycle of care — MBS Online; document results and act on abnormal findings.
• Ankle-brachial index (ABI) — screen for concurrent peripheral arterial disease; ABI below 0.9 indicates significant arterial disease requiring vascular review.
• Podiatry referral — for callus, cracked heels, nail problems, fungal infection, ulceration, or any patient unable to self-inspect.
• High-risk foot classification — reduced protective sensation plus structural deformity plus previous ulcer or amputation equals high risk; multidisciplinary hospital foot service referral.

Charcot neuroarthropathy: Acute Charcot foot presents as a warm, erythematous, swollen foot in a patient with diabetes and peripheral neuropathy, sometimes without systemic signs of infection. It is a medical emergency requiring same-day immobilisation (total contact cast) and specialist endocrinology or orthopaedic referral. The most common error is misdiagnosis as cellulitis, allowing progressive bone and joint destruction to continue unchecked.

Glycaemic control and neuropathy: Per eTG, individualised HbA1c targets — typically around 7% — balance hypoglycaemia risk against long-term microvascular benefit. The DCCT trial (type 1 diabetes) established that tight glycaemic control substantially reduces both the incidence and progression of peripheral neuropathy. Evidence in type 2 diabetes (UKPDS, ACCORD) shows benefit for primary prevention of neuropathy, with more modest effects on established disease.

D. Australian operations

PBS-listed pharmacotherapy

Per PBS Australia:

• Pregabalin (Lyrica) — Authority Required for refractory neuropathic pain; requires documented failure of amitriptyline 50 mg/day plus at least one of carbamazepine, valproate, or gabapentin; SafeScript / real-time prescription monitoring (RTPM) — check before every prescription.
• Gabapentin — Authority Required for refractory neuropathic pain after pregabalin failure or ineligibility; SafeScript / RTPM.
• Duloxetine (Cymbalta) — PBS Authority for diabetic peripheral neuropathic pain (separate from depression/GAD Authority pathway).
• Amitriptyline — PBS general schedule; prescribed off-label for neuropathic pain — write the indication on the script.
• Hydroxocobalamin IM — PBS-listed for confirmed vitamin B12 deficiency; 1000 mcg given at 1–3 month intervals.
• Carbamazepine — PBS general schedule for trigeminal neuralgia and epilepsy.

MBS items

Per MBS Online:

• Standard consultations — items 23, 36, 44 — assessment and ongoing management.
• GP Chronic Condition Management Plan (GPCCMP) — items 965/967 — chronic neuropathy or chronic pain qualifies; up to 5 allied health visits per year (podiatry, physiotherapy, OT, psychology, dietitian).
• Better Access Mental Health Care Plan — item 2715 — for comorbid depression, anxiety, or chronic pain-related psychological distress.
• Diabetes Annual Cycle of Care — includes monofilament foot examination.
• NCS/EMG — Medicare-rebatable via specialist (neurology) referral.
• 75+ Health Assessment — item 707 — includes falls screening and neurological assessment.
• ATSI Health Assessment — item 715 — includes neuropathy risk assessment in First Nations patients with diabetes.

Driving

Austroads Assessing Fitness to Drive (2022) specifies that significant lower-limb proprioceptive loss or motor weakness may impair safe vehicle operation. GPs should document fitness-to-drive assessment, the discussion held with the patient, and any conditions placed on driving in the medical record.

E. Special populations

Older adults. Peripheral neuropathy in patients aged over 70 demands particular attention to falls prevention: occupational therapy home assessment, bathroom safety rails, removal of floor rugs, vision and blood pressure review, and polypharmacy review. Diabetes Australia emphasises that older patients with diabetic neuropathy require lower footwear thresholds for specialist referral. Pregabalin and amitriptyline carry elevated risk of sedation, peripheral oedema, and falls in this age group — start at half-dose and titrate cautiously. Any older patient with new unexplained neuropathy warrants SPEP and immunofixation to exclude paraproteinaemia.

People on metformin. Metformin reduces intestinal absorption of vitamin B12 over time. Annual B12 monitoring is recommended for patients on long-term metformin — particularly important because many patients with type 2 diabetes and peripheral neuropathy are simultaneously B12-deficient from metformin use, creating a compounding and partly reversible deficit.

Pregnancy. Pregabalin and gabapentin are generally avoided in pregnancy due to limited safety data; specialist input is required for neuropathic pain management in pregnant patients. Hydroxocobalamin replacement for confirmed B12 deficiency is safe in pregnancy. Diabetic neuropathy may worsen transiently during pregnancy; multidisciplinary obstetric-endocrinology care is the standard approach.

Children and adolescents. Peripheral neuropathy in paediatric patients requires specialist paediatric neurology input. Hereditary neuropathies (CMT) often present in childhood or adolescence with pes cavus, hammer toes, distal weakness, and delayed motor milestones — family history review and genetic testing are central to assessment.

When to escalate

Present to hospital emergency:

• Acute ascending weakness with loss of deep tendon reflexes — Guillain-Barré syndrome is a life-threatening emergency; respiratory failure can develop within hours to days. Emergency presentation is required for any patient with subacute ascending motor weakness and areflexia.
• Acute Charcot foot — warm, erythematous, swollen foot in a patient with diabetes; same-day immobilisation is essential to prevent progressive bone destruction.

Neurologist referral:

• Diagnostic uncertainty after a complete GP workup
• Demyelinating pattern suspected (rapid onset, proximal involvement, significant motor deficit)
• Suspected CIDP, vasculitic neuropathy, paraneoplastic neuropathy, or hereditary neuropathy
• NCS/EMG required for classification and diagnostic confirmation
• Neuropathic pain inadequately controlled despite adequate trials of two or more first-line agents

Pain medicine referral:

• Refractory neuropathic pain despite optimised first-line pharmacotherapy and multimodal management
• Spinal cord stimulator candidacy assessment

What this article is and is not

This is general health information based on current Australian general practice guidelines — Therapeutic Guidelines (eTG), Australian Medicines Handbook (AMH), RACGP, NPS MedicineWise, Diabetes Australia, and the Finnerup et al. NeuPSIG neuropathic pain guidelines (Lancet Neurology 2015). It does not constitute personal medical advice and does not create a doctor–patient relationship. Treatment decisions are made with your own GP and treating team.

For consumer resources: HealthDirect — Peripheral neuropathy, Diabetes Australia — Foot care, NPS MedicineWise.

---

Sources cited

1. Therapeutic Guidelines (eTG) — Neurology: neuropathic pain and trigeminal neuralgia
2. RACGP — Peripheral neuropathy resources
3. Australian Medicines Handbook (AMH)
4. Faculty of Pain Medicine ANZCA — Opioid and neuropathic pain position statements
5. Finnerup NB et al. — Pharmacotherapy for neuropathic pain: NeuPSIG systematic review and meta-analysis (Lancet Neurol 2015)
6. PBS — Pregabalin, gabapentin, duloxetine, hydroxocobalamin
7. MBS Online — GPCCMP, Diabetes Annual Cycle of Care, NCS/EMG pathway
8. Diabetes Australia — Foot care guidance
9. HealthDirect — Peripheral neuropathy
10. NPS MedicineWise
11. Austroads — Assessing Fitness to Drive 2022