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Acute Neuropathic Pain

Last updated 1 Jun 2026 · Pain & analgesia

📋 Key Information Summary

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  • Early recognition of acute neuropathic pain is critical — delayed treatment increases the risk of central sensitisation, opioid misuse, and transition to chronic neuropathic pain.
  • Neuropathic pain features include burning, shooting, electric-shock, tingling, numbness, allodynia, and hyperalgesia in a neuroanatomical distribution.
  • Use the DN4 (Douleur Neuropathique 4) or PainDETECT screening tool at initial assessment; a score ≥ 4/10 on DN4 suggests neuropathic pain.
  • Gabapentinoids (pregabalin, gabapentin) are first-line pharmacotherapy for acute neuropathic pain; start low and titrate to effect to minimise CNS side-effects.
  • Pregabalin 75 mg BD, titrated to 150–300 mg BD, offers faster onset than gabapentin; both require dose reduction in renal impairment.
  • TCAs (amitriptyline 10–25 mg nocte, nortriptyline 10–25 mg nocte) are effective but carry anticholinergic and cardiac risks — avoid in the elderly and those with cardiac conduction defects.
  • Duloxetine 60 mg daily and venlafaxine 150–225 mg daily (SNRIs) are alternatives when TCAs are contraindicated; particularly useful when comorbid depression is present.
  • Combination therapy (gabapentinoid + TCA or SNRI) may be needed for refractory symptoms, but increases adverse-effect burden.
  • Ketamine (sub-anaesthetic IV infusion 0.1–0.3 mg/kg/hr) is reserved for specialist/hospital settings for refractory acute neuropathic pain, burns-related pain, or complex regional pain syndrome.
  • Opioids are not first-line for neuropathic pain; if used, prescribe at the lowest effective dose for the shortest duration with a clear exit strategy.
  • Aboriginal and Torres Strait Islander Australians experience higher rates of neuropathic pain due to diabetic neuropathy and chronic kidney disease; culturally safe access and multimodal management are essential.
  • Assess for reversible causes (nerve compression, infection, metabolic derangement) and refer for specialist evaluation when diagnosis is uncertain or pain is escalating.

Introduction & Australian Epidemiology

Neuropathic pain is defined by the International Association for the Study of Pain (IASP) as pain caused by a lesion or disease of the somatosensory nervous system. Acute neuropathic pain arises in the context of recent nerve injury — such as surgery, trauma, acute herpes zoster, radiculopathy, or acute diabetic neuropathy — and must be distinguished from nociceptive pain to ensure appropriate treatment and avoid inappropriate opioid escalation.

In Australia, neuropathic pain affects an estimated 5–8% of the general population, with higher prevalence among those with diabetes mellitus, HIV, and chronic kidney disease. Post-surgical neuropathic pain occurs in up to 10–50% of patients following procedures such as mastectomy, thoracotomy, and inguinal hernia repair. Acute herpes zoster affects approximately 300,000 Australians annually, with 10–20% developing significant neuropathic pain during the acute phase.

The Australian Institute of Health and Welfare (AIHW) reports that neuropathic pain is a leading contributor to opioid initiation in primary care, and early evidence-based management with non-opioid agents can reduce opioid dependence and prevent the transition to chronic pain. The National Pain Strategy (2010) and the updated Australian Pain Society guidelines emphasise a multidisciplinary, biopsychosocial approach with pharmacotherapy as one component of a broader management plan.

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Opioid avoidance: Neuropathic pain responds poorly to opioids alone. Early initiation of neuropathic-specific agents (gabapentinoids, TCAs, SNRIs) reduces the likelihood of opioid dose escalation and chronic dependence. Where opioids are used, set clear treatment goals, review at 48–72 hours, and plan an exit strategy.

Common Causes of Acute Neuropathic Pain in Australia

Cause Key Features Typical Setting
Acute herpes zoster Dermatomal burning/ lancinating pain ± vesicular rash GP, ED
Post-surgical neuropathy Burning, numbness, allodynia in surgical field (24–72 hrs post-op) Post-anaesthesia care, surgical ward
Acute radiculopathy Shooting pain in dermatomal distribution, ± motor weakness GP, ED, musculoskeletal clinic
Diabetic lumbosacral radiculoplexus neuropathy Severe unilateral thigh/hip pain with weight loss in T2DM Endocrinology, neurology
Nerve compression (e.g. tumour, haematoma) Acute onset neuropathic features in nerve distribution ED, oncology
Chemotherapy-induced peripheral neuropathy (acute onset) Distal tingling/ burning after vincristine, oxaliplatin, paclitaxel Oncology day unit
Complex regional pain syndrome (CRPS) Disproportionate pain, swelling, colour change, allodynia post-injury ED, pain medicine

Recognition of Acute Neuropathic Pain

Early identification of neuropathic pain is essential because the neurobiological mechanisms differ fundamentally from nociceptive pain, and first-line treatments are distinct. Failure to recognise neuropathic pain leads to inappropriate analgesic prescribing — particularly opioid escalation — and increases the risk of chronification through central sensitisation.

Clinical Features Suggesting Neuropathic Pain

The hallmark descriptors of neuropathic pain include:

  • Spontaneous (stimulus-independent) pain: burning, shooting, electric-shock-like, tingling, or "pins and needles"
  • Evoked (stimulus-dependent) pain: allodynia (pain from a non-painful stimulus, e.g. light touch, clothing) and hyperalgesia (exaggerated pain response to a painful stimulus)
  • Sensory deficits: numbness, hypoaesthesia, or dysaesthesia in a neuroanatomical (dermatomal or peripheral nerve) distribution
  • Temporal patterns: paroxysmal lancinating attacks, or continuous burning worse at night
  • Autonomic features: changes in skin colour, temperature, sweating, or oedema (suggesting CRPS)

Screening and Assessment Tools

Validated screening tools assist in identifying neuropathic pain components, particularly in primary care where bedside neurological examination may be limited. These tools should be used in conjunction with clinical assessment, not as a standalone diagnostic test.

Tool Items Cutoff Sensitivity / Specificity Best Setting
DN4 (Douleur Neuropathique 4) 10 items (7 interview, 3 examination) ≥ 4/10 83% / 90% Primary care, ED
PainDETECT 9 items (self-report) ≥ 19 = likely neuropathic 85% / 80% Primary care (no examination needed)
LANSS (Leeds Assessment of Neuropathic Symptoms and Signs) 7 items (5 symptom, 2 examination) ≥ 12/24 82% / 87% Pain clinic, GP
NPQ (Neuropathic Pain Questionnaire) 12 items (self-report) ≥ 1 point 66% / 74% Research, secondary care

Bedside Neurological Examination

A focused examination should include:

  1. Light touch: cotton wool — test for hypoaesthesia and allodynia
  2. Pinprick: disposable neurotip — test for hypalgesia and hyperalgesia
  3. Brush test: paintbrush stroke — dynamic mechanical allodynia (hallmark of central sensitisation)
  4. Vibration: 128 Hz tuning fork on bony prominences — dorsal column function
  5. Temperature: cold metal object — small fibre assessment
  6. Reflexes: deep tendon reflexes (absent ankle reflexes in peripheral neuropathy)
  7. Motor examination: power in affected nerve distribution (to exclude compressive lesions requiring urgent intervention)
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Red flags requiring urgent imaging and specialist referral: Progressive motor weakness, cauda equina features (saddle anaesthesia, bladder/bowel dysfunction), acute onset in immunocompromised patients (consider abscess, opportunistic infection), or pain with systemic features (fever, weight loss) suggesting malignancy or infection. Refer to ED or arrange urgent MRI.

Diagnostic Workup

Investigations should be guided by the suspected underlying cause:

Essential HbA1c, fasting glucose Screen for diabetic neuropathy — available in all Australian pathology services
Essential eGFR, serum creatinine, electrolytes Exclude uraemic neuropathy; guide gabapentinoid dosing
Essential FBC, ESR, CRP Exclude infection, inflammation, haematological causes
Available B12, folate, TFTs Metabolic causes of peripheral neuropathy — MBS item 66556
Available Nerve conduction studies / EMG Confirm peripheral neuropathy, localise lesion — neurologist or rehabilitation specialist; MBS item 11005
Referral MRI spine (with contrast) When radiculopathy, cord compression, or cauda equina suspected — bulk-billed in public hospitals
Specialist Quantitative sensory testing (QST) Small fibre assessment — available at major pain medicine centres

Gabapentinoids — Pregabalin & Gabapentin

Gabapentinoids (pregabalin and gabapentin) are first-line pharmacological agents for acute neuropathic pain. They bind to the α2δ subunit of voltage-gated calcium channels, reducing excitatory neurotransmitter release in the dorsal horn. They are effective across a range of neuropathic pain aetiologies, including postherpetic neuralgia, post-surgical neuropathic pain, and diabetic peripheral neuropathy.

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Regulatory note (2024): Pregabalin and gabapentin are classified as Schedule 4 (Prescription Only) in all Australian states and territories. Following concerns regarding misuse and diversion, several jurisdictions (including Queensland, Victoria, and Western Australia) have implemented real-time prescription monitoring (RTPM) programs that include gabapentinoids. Clinicians should check their state's RTPM system (e.g. QScript, SafeScript, ScriptCheck) before prescribing, particularly for patients on concurrent opioids or benzodiazepines.

Pregabalin

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Pregabalin
Lyrica® · Generic available · α2δ ligand (gabapentinoid)
Adult dose Start 75 mg PO BD; titrate to 150 mg BD after 3–7 days; max 300 mg BD (600 mg/day)
Paediatric dose Not routinely recommended < 18 years; limited evidence; specialist guidance only
Route Oral (capsules: 25, 75, 150, 300 mg)
Duration Acute: 4–8 weeks initial trial; reassess at 4 weeks for response. Taper over ≥ 1 week to discontinue.
Renal adjustment eGFR 30–60: max 150 mg BD; eGFR 15–30: 25–75 mg OD–BD; eGFR < 15: 25 mg OD; HD: 25–50 mg post-dialysis
Hepatic adjustment Not required (minimal hepatic metabolism)
Key adverse effects Somnolence, dizziness, peripheral oedema, weight gain, blurred vision, cognitive impairment
PBS status 🔶 PBS Authority Required — for neuropathic pain where other first-line agents have failed or are contraindicated

Gabapentin

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Gabapentin
Neurontin® · Generic available · α2δ ligand (gabapentinoid)
Adult dose Start 300 mg PO OD (nocte); increase to 300 mg BD, then 300 mg TDS over 1–2 weeks; titrate to 600 mg TDS (1,800 mg/day); max 3,600 mg/day in divided doses
Paediatric dose ≥ 6 years: 10 mg/kg/day in 3 divided doses; titrate to 25–35 mg/kg/day (max 50 mg/kg/day); specialist initiation recommended
Route Oral (capsules: 100, 300, 400 mg; tablets: 600, 800 mg; oral liquid available)
Duration Acute: 4–8 weeks; reassess response at 4 weeks. Taper over ≥ 1 week.
Renal adjustment eGFR 30–60: 200–700 mg BD; eGFR 15–30: 200–700 mg OD; eGFR < 15: 100–300 mg OD; HD: supplemental dose post-dialysis (125–350 mg)
Hepatic adjustment Not required (renally excreted unchanged)
Key adverse effects Somnolence, dizziness, ataxia, peripheral oedema, nausea; slower titration reduces early CNS effects
PBS status 🔶 PBS Authority Required — for treatment of neuropathic pain

Pregabalin vs Gabapentin — Comparison

Feature Pregabalin Gabapentin
Bioavailability ≥ 90% (linear pharmacokinetics) 33–66% (non-linear, saturable absorption)
Onset to effect Rapid — effect within hours to days of titration Slower — may require 1–2 weeks of titration
Dosing frequency BD TDS (more frequent dosing)
Renal adjustment Required (simpler adjustments) Required (more complex calculations)
Oral liquid formulation Not available in Australia Available (beneficial for NG tube / dysphagia)
Misuse potential Higher (faster onset, euphoria reported) Lower but still present
Approximate PBS cost (30 days) –30 (generic) –20 (generic)
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Tapering advice: Always taper gabapentinoids before discontinuation — abrupt cessation after ≥ 1 week of use can cause withdrawal symptoms (anxiety, insomnia, nausea, diaphoresis, pain exacerbation). Taper pregabalin by 75 mg every 3–7 days; taper gabapentin by 300 mg every 3–7 days.

Tricyclic Antidepressants & SNRIs

Tricyclic antidepressants (TCAs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are second-line agents for acute neuropathic pain, or first-line in patients who cannot tolerate gabapentinoids. Their analgesic effect in neuropathic pain is independent of their antidepressant action and occurs at lower doses, with an earlier onset of analgesia (1–2 weeks) compared to antidepressant effects (4–6 weeks).

Tricyclic Antidepressants (TCAs)

TCAs (amitriptyline, nortriptyline) enhance descending inhibitory pain pathways through noradrenaline and serotonin reuptake inhibition. They are effective across multiple neuropathic pain conditions but their use is limited by anticholinergic side-effects and cardiac toxicity.

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Amitriptyline
Endep® · Trypizol® · TCA
Adult dose (neuropathic pain) 10–25 mg PO nocte; titrate by 10–25 mg every 1–2 weeks; target 25–75 mg nocte; max 150 mg/day
Paediatric dose Not recommended for neuropathic pain < 12 years; ≥ 12 years: 10 mg nocte, specialist initiation
Route Oral (tablets: 10, 25, 50 mg)
Duration Trial of ≥ 6–8 weeks at adequate dose before declaring non-response; taper to cease
Renal adjustment None specifically recommended; use with caution in CKD (increased sensitivity)
Hepatic adjustment Avoid in severe hepatic impairment; reduce dose in mild–moderate impairment
Key adverse effects Dry mouth, constipation, urinary retention, sedation, weight gain, orthostatic hypotension, QT prolongation, cardiac arrhythmia in overdose
PBS status ✔ PBS General Benefit
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Nortriptyline
Allegron® · TCA (secondary amine)
Adult dose (neuropathic pain) 10–25 mg PO nocte; titrate by 10–25 mg weekly; target 50–100 mg nocte; max 150 mg/day
Paediatric dose Not recommended < 12 years; specialist use only
Route Oral (capsules: 10, 25, 50, 75 mg)
Renal adjustment No specific adjustment; monitor closely in severe CKD
Hepatic adjustment Reduce dose in hepatic impairment
Key advantages over amitriptyline Less sedation, less anticholinergic burden — better tolerated in the elderly
PBS status ✔ PBS General Benefit
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Contraindications to TCAs: Known cardiac conduction defects (second/third-degree heart block, bundle branch block), recent MI (< 3 months), QTc > 450 ms, concurrent MAOIs, severe hepatic impairment, urinary retention (prostatic hypertrophy), narrow-angle glaucoma. Obtain an ECG before initiation in patients aged > 50 years or with cardiac risk factors. TCAs are highly lethal in overdose — consider this risk when prescribing for patients with suicidality.

Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs)

SNRIs (duloxetine, venlafaxine) have a more favourable safety profile than TCAs and are preferred in patients with cardiovascular comorbidities, the elderly, or those at overdose risk. They are particularly useful when neuropathic pain coexists with depression or anxiety.

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Duloxetine
Cymbalta® · Generic available · SNRI
Adult dose (neuropathic pain) Start 30 mg PO daily for 1 week, then increase to 60 mg daily; max 120 mg/day (rarely needed for analgesia)
Paediatric dose Not recommended for neuropathic pain < 18 years in Australia
Route Oral (enteric-coated capsules: 30, 60 mg — do not crush or open)
Duration Minimum 4–6 weeks trial; if effective, continue 3–6 months, then reassess. Taper over ≥ 2 weeks.
Renal adjustment Avoid if eGFR < 30 mL/min (accumulation of metabolites)
Hepatic adjustment Contraindicated in hepatic impairment (hepatotoxicity risk)
Key adverse effects Nausea (most common, ~25%), dry mouth, constipation, dizziness, insomnia, diaphoresis, sexual dysfunction, hepatotoxicity (rare)
PBS status 🔶 PBS Authority Required — for neuropathic pain; General Benefit for depression/MDD
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Venlafaxine
Effexor-XR® · Generic available · SNRI
Adult dose (neuropathic pain) Start 37.5–75 mg PO daily (extended-release); titrate by 75 mg weekly; target 150–225 mg daily
Paediatric dose Not recommended for neuropathic pain < 18 years
Route Oral (XR capsules: 37.5, 75, 150 mg; IR tablets: 37.5, 75 mg)
Renal adjustment Reduce dose by 50% if eGFR 10–30; avoid if eGFR < 10
Hepatic adjustment Reduce dose by 50% in mild–moderate impairment; avoid in severe impairment
Key adverse effects Nausea, headache, dizziness, insomnia, hypertension (dose-related), sexual dysfunction, discontinuation syndrome (more severe than other SNRIs)
PBS status ✔ PBS General Benefit (for depression; neuropathic pain use may require private prescription or authority depending on indication coding)

Combination Therapy

When monotherapy with either a gabapentinoid or TCA/SNRI is inadequate, combining agents from different classes may provide additive benefit. Evidence from the COMBO-DN trial supports combination gabapentin + nortriptyline or gabapentin + morphine for refractory neuropathic pain, though with increased adverse effects. In the acute setting:

  • Gabapentinoid + TCA: most commonly used combination; monitor for cumulative sedation and anticholinergic effects
  • Gabapentinoid + SNRI: useful when TCA contraindicated; watch for serotonin-related adverse effects
  • Avoid TCA + SNRI combination: serotonin syndrome risk
  • Add topical agents (lidocaine 5% patch/plaster, capsaicin 8% patch) for localised neuropathic pain as adjunctive therapy
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Topical lidocaine 5%: Useful for localised allodynia (e.g. postherpetic neuralgia). Up to 3 plasters applied for 12 hours on / 12 hours off. Minimal systemic absorption. PBS Authority Required for postherpetic neuralgia. Apply only to intact, non-inflamed skin.

Ketamine — Specialist Use

Ketamine is a non-competitive NMDA (N-methyl-D-aspartate) receptor antagonist that is used in sub-anaesthetic doses for the management of refractory acute neuropathic pain. Its role is primarily in hospital and specialist pain medicine settings due to its side-effect profile, monitoring requirements, and the need for IV administration. Ketamine is not appropriate for primary care prescribing for chronic neuropathic pain.

Indications for Ketamine in Acute Neuropathic Pain

  • Refractory acute neuropathic pain unresponsive to gabapentinoids + TCA/SNRI ± opioids
  • Acute exacerbation of CRPS (complex regional pain syndrome) — strongest evidence base
  • Severe acute postherpetic neuralgia with significant functional impairment
  • Acute neuropathic pain in opioid-tolerant patients (e.g. cancer-related neuropathic pain with opioid tolerance)
  • Post-surgical neuropathic pain refractory to standard multimodal analgesia (e.g. post-thoracotomy, post-mastectomy)
  • Burns-related procedural pain with neuropathic features (dressing changes)

Dosing Protocols

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Ketamine (IV infusion)
Ketalar® · Generic available · NMDA receptor antagonist
Sub-anaesthetic dose (adult) Loading: 0.1–0.3 mg/kg IV over 15–30 min; infusion: 0.1–0.3 mg/kg/hr for 2–4 hours. Can repeat daily for up to 3–5 days as inpatient.
Multi-day infusion (adult) Continuous IV 0.1–0.3 mg/kg/hr for 3–5 days with daily review; typically under pain medicine specialist supervision in HDU/ICU
Paediatric dose Sub-anaesthetic: 0.1–0.25 mg/kg/hr IV; paediatric pain specialist supervision required
Route IV infusion (primary); subcutaneous and intranasal routes used in specialist settings. Oral bioavailability ~20% — used for outpatient weaning.
Renal adjustment Use with caution; active metabolite (norketamine) accumulates in CKD. Reduce dose by 50% if eGFR < 30.
Hepatic adjustment Reduce dose in severe hepatic impairment (prolonged half-life)
Key adverse effects Dissociation (psychotomimetic), nausea/vomiting, hypertension, tachycardia, increased ICP, emergence reactions, hepatotoxicity (rare, multi-day infusions), urological toxicity (chronic use)
PBS status ❌ Not PBS listed for chronic pain — hospital authority / HSD funding for inpatient use
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Monitoring requirements for IV ketamine: Continuous pulse oximetry, ECG, and non-invasive blood pressure monitoring during infusion. Mental status assessment every 15–30 minutes during loading dose. Airway management equipment must be immediately available. Admit to HDU/ICU for multi-day infusions. Assess for psychotomimetic symptoms (hallucinations, derealisation) — co-administer low-dose midazolam (1–2 mg IV) or clonidine if distressing. Obtain baseline LFTs and repeat if infusions > 48 hours.

Contraindications to Ketamine

  • Uncontrolled systemic hypertension (ketamine raises BP and HR via sympathetic stimulation)
  • Raised intracranial pressure or unstable intracranial pathology
  • Severe psychiatric illness (schizophrenia, active psychosis) — relative contraindication
  • Severe hepatic impairment (Child-Pugh C)
  • Known hypersensitivity
  • Pregnancy — avoid unless benefits clearly outweigh risks (Category B3)

Alternative Agents for Refractory Acute Neuropathic Pain

Agent Dose Setting Key Notes
IV lidocaine (lignocaine) 1–1.5 mg/kg IV over 30–60 min, then 1–2 mg/kg/hr Inpatient; cardiology/HDU monitoring Evidence for CRPS, postherpetic neuralgia; requires cardiac monitoring
Mexiletine 150 mg PO TDS, titrate to max 300 mg TDS Specialist initiation; oral lidocaine analogue Not PBS listed; cardiac monitoring recommended; niche use
Clonidine 25–75 µg PO TDS; or 75–150 µg epidural Inpatient / pain specialist α2-agonist; useful adjunct; hypotension risk
Capsaicin 8% patch (Qutenza®) Single application for 30–60 min (peripheral neuropathy) or 60 min (PHN) Pain clinic / GP (trained application) PBS Authority Required for PHN; desensitises TRPV1 receptors; effect lasts up to 3 months

Special Populations

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Pregnancy

Pregabalin / Gabapentin Category B3 — limited human data; avoid unless benefit clearly outweighs risk. Neonatal withdrawal reported. Avoid in first trimester if possible.
Amitriptyline / Nortriptyline Category C — generally considered low risk in later pregnancy; avoid near term (neonatal withdrawal). Nortriptyline preferred (less anticholinergic effect).
Duloxetine Category B3 — avoid in third trimester (neonatal withdrawal syndrome, respiratory distress). Not first-line in pregnancy.
Ketamine Category B3 — avoid unless essential; may cause uterine hypertonus at higher doses. Specialist decision only.
Preferred approach Paracetamol ± low-dose amitriptyline. Topical lidocaine for localised pain (minimal systemic absorption). Multidisciplinary pain team involvement recommended.
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Paediatrics

Gabapentin Evidence in paediatric neuropathic pain is limited; dosing: 10 mg/kg/day titrated to 25–35 mg/kg/day TDS (max 50 mg/kg/day). Specialist initiation recommended. Available as oral liquid.
Pregabalin Limited paediatric data; not TGA-approved for use < 18 years for neuropathic pain. Specialist use only.
Amitriptyline Not recommended < 12 years for neuropathic pain. ≥ 12 years: 10 mg nocte, specialist initiation. Monitor ECG.
Ketamine Sub-anaesthetic doses used in paediatric pain centres; 0.1–0.25 mg/kg/hr IV. Requires paediatric HDU/ICU-level monitoring.
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Elderly (≥ 65 years)

Gabapentinoids Start at half the usual adult dose; slow titration (e.g. gabapentin 100 mg nocte → 100 mg BD → 100 mg TDS). Increased fall risk — assess gait and balance at each visit. Dose-adjust for renal function (eGFR frequently reduced).
TCAs Avoid amitriptyline in patients ≥ 65 years (Beers criteria). Nortriptyline (10–25 mg nocte) preferred if TCA needed. Obtain baseline ECG. Anticholinergic burden is additive with other medications — use anticholinergic burden calculators.
Duloxetine Generally well tolerated; start 30 mg daily for 2 weeks before increasing to 60 mg. Avoid if eGFR < 30. Risk of hyponatraemia (SIADH) — check sodium at 2 and 4 weeks.
Ketamine Use with extreme caution — increased risk of hallucinations, hypertension, and cognitive disturbance. Reduce dose by 50%. Specialist-only use.
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Renal Impairment

Pregabalin Must be dose-adjusted (see gabapentinoid section). Dialysable — give supplemental dose post-HD.
Gabapentin Must be dose-adjusted (see gabapentinoid section). Dialysable — supplemental dose post-HD (125–350 mg).
Duloxetine Avoid if eGFR < 30 mL/min (metabolite accumulation)
TCAs Use with caution; increased sensitivity in uraemia; nortriptyline preferred. Monitor for excessive sedation.
Uraemic neuropathy Ensure dialysis adequacy; consider optimising B12, folate, and phosphate levels. Renal team co-management essential.
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Hepatic Impairment

Duloxetine Contraindicated in hepatic impairment (hepatotoxicity risk)
Venlafaxine Reduce dose by 50% in mild–moderate impairment; avoid in severe impairment
TCAs Reduce dose; avoid amitriptyline in severe hepatic impairment. Nortriptyline may be cautiously used.
Gabapentinoids Minimal hepatic metabolism — gabapentin preferred in significant hepatic impairment (renally excreted unchanged)
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Immunocompromised

Considerations Higher prevalence of neuropathic pain (HIV-associated neuropathy, CMV polyneuropathy, post-transplant neuropathy, chemotherapy-induced). Careful drug interaction review with antiretrovirals and immunosuppressants.
Gabapentinoids Generally safe; no significant interactions with antiretrovirals or calcineurin inhibitors.
TCAs/SNRIs Check interactions with protease inhibitors (CYP2D6 inhibition); fluconazole (used in transplant) may increase TCA levels.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health
Higher disease burden
Aboriginal and Torres Strait Islander Australians experience a significantly higher prevalence of neuropathic pain driven by higher rates of type 2 diabetes mellitus (3–4× higher than non-Indigenous Australians), chronic kidney disease, and trachoma-related corneal neuropathy. Diabetic peripheral neuropathy is the most common cause of neuropathic pain in remote communities. The AIHW reports that diabetes-related hospitalisations are 3–6 times higher for Indigenous Australians.
Remote and rural access
Many Aboriginal and Torres Strait Islander people live in remote and very remote areas where access to specialist pain services, neurologists, and allied health is limited. Telehealth pain medicine consultations (MBS items 99202–99215) are critical. Primary care clinicians, including Aboriginal Health Practitioners (AHPs), play a central role in neuropathic pain recognition and initial management. Where specialist referral is needed, coordination through the local Aboriginal Community Controlled Health Service (ACCHS) and Royal Flying Doctor Service (RFDS) is essential.
Cultural safety in pain assessment
Pain expression varies across cultures; some Aboriginal and Torres Strait Islander patients may under-report pain due to stoicism, previous negative healthcare experiences, or different cultural frameworks for understanding pain. Use culturally validated tools where available, involve Aboriginal Health Workers/Practitioners in assessment, and employ yarning (a culturally grounded communication approach) as a framework for understanding the patient's pain experience and its impact on their life and community role.
Opioid risk and NT prescribing
The Northern Territory has the highest opioid dispensing rate per capita in Australia. Early identification and treatment of neuropathic pain with neuropathic-specific agents (gabapentinoids, TCAs, SNRIs) may reduce the burden of opioid-related harm in Aboriginal communities. Real-time prescription monitoring (RTPM) and the NT's SafeScript program assist in preventing high-risk prescribing combinations.
Multimodal and holistic approaches
Integrate pharmacotherapy with culturally appropriate non-pharmacological strategies: social and emotional wellbeing programs, traditional healing practices (where the patient's preference), exercise programs, and community-based chronic disease management. The National Aboriginal Community Controlled Health Organisation (NACCHO) and RHDAustralia guidelines support a holistic model of care. Programs such as the Deadly Choices initiative and Close the Gap chronic disease frameworks are relevant to long-term pain management.
Renal dose adjustment
CKD stages 3–5 are 2–3 times more prevalent in Aboriginal and Torres Strait Islander Australians. Since gabapentinoids are renally cleared, mandatory renal dose adjustment is frequently required. Check eGFR before initiating and at each dose change. Coordinate with renal services where available (e.g. Menzies School of Health Research programs in the NT).

📚 References

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  9. 9. Moore RA, Wiffen PJ, Derry S, Toelle T, Rice AS. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014;(4):CD007938.
  10. 10. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009;(3):CD007076.
  11. 11. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;(7):CD008242.
  12. 12. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;(1):CD007115.
  13. 13. Orhurhu V, Orhurhu MS, Bhatia A, Cohen SP. Ketamine infusions for chronic pain: a systematic review and meta-analysis of randomized controlled trials. Anesth Analg. 2019;129(1):241-254.
  14. 14. Connolly SB, Gallagher NA, McCormick D, et al. Combination pharmacotherapy for neuropathic pain: a Cochrane review. Pain. 2023;164(7):1443-1457.
  15. 15. Therapeutic Goods Administration (TGA). Pregabalin scheduling delegate's interim decisions and invitation for further comment. Canberra: Department of Health; 2023.
  16. 16. National Aboriginal Community Controlled Health Organisation (NACCHO). National guide to a preventive health assessment for Aboriginal and Torres Strait Islander people. 3rd ed. Melbourne: RACGP; 2018.
  17. 17. Royal Australian College of General Practitioners (RACGP). Prescribing drugs of dependence in general practice, Part B — Benzodiazepines, gabapentinoids and opioids. Melbourne: RACGP; 2022.
  18. 18. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162-173.
for PBS scripts. Utilise ACCHS pharmacies and Remote Area Aboriginal Health Worker programs for medication supply in remote areas. Avoid initiating benzodiazepines; support holistic pain management including community-based exercise programs.
Preventive health
Promote bone health: encourage vitamin D supplementation (1000 IU daily in deficient individuals), smoking cessation support, reduction of alcohol intake, and weight-bearing exercise. MBS Item 715 health checks provide a structured opportunity to assess bone health, screen for osteoporosis risk factors, and discuss musculoskeletal health in a culturally safe context.

Quick Reference: Differential Diagnosis at a Glance

Costovertebral dysfunction
Paracetamol ± NSAID; manual therapy
2–6 weeks
Provocable on palpation; no red flags
Thoracic compression fracture
Paracetamol; ± calcitonin; DXA + osteoporosis Rx
6–12 weeks healing
Elderly; osteoporosis; acute onset
ACS (posterior MI)
Aspirin 300 mg, GTN, heparin; urgent PCI
Time-critical
ECG, troponin; CV risk factors
Aortic dissection
IV labetalol; urgent CT aortogram; surgery (Type A)
Time-critical
Tearing pain; BP differential >20 mmHg
Vertebral osteomyelitis
IV antibiotics (vancomycin + ceftriaxone initially); ID consult
6 weeks IV antibiotics
Fever, elevated CRP, IV drug use
Biliary colic / cholecystitis
Paracetamol ± morphine; lap cholecystectomy
Surgical within 72 h (cholecystitis)
RUQ/infrascapular; post-prandial; RUQ US

📚 References

  1. 1. Briggs AM, Smith AJ, Straker LM, Bragge P. Thoracic spine pain in the general population: prevalence, incidence and associated factors in children, adolescents and adults. A systematic review. BMC Musculoskelet Disord. 2009;10:77.
  2. 2. National Health and Medical Research Council (NHMRC). Evidence-based management of acute musculoskeletal pain. Canberra: NHMRC; 2003 (updated 2020).
  3. 3. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework: Summary report 2023. Canberra: AIHW; 2023.
  4. 4. Deyo RA, Rainville J, Kent DL. What can the history and physical examination tell us about low back pain? JAMA. 1992;268(6):760–765.
  5. 5. Stochkendahl MJ, Kjaer P, Hartvigsen J, et al. National Clinical Guidelines for non-surgical treatment of patients with recent onset low back pain or lumbar radiculopathy. Europ Spine J. 2018;27(1):60–75.
  6. 6. Erwin WM, Jackson PC, Homonko DA. Innervation of the human costovertebral joint: implications for clinical back pain syndromes. J Manipulative Physiol Ther. 2000;23(6):395–403.
  7. 7. Royal Australian College of General Practitioners (RACGP). Guidelines for preventive activities in general practice. 9th edn. Melbourne: RACGP; 2018 (updated 2023).
  8. 8. Hirsch JA, Singh V, Falco FJE, et al. Thoracic facet joint interventions. Pain Physician. 2016;19(4):E581–E593.
  9. 9. Erwin WM, Jackson PC. The costovertebral joint: anatomy, biomechanics, and clinical significance in thoracic back pain syndromes. J Can Chiropr Assoc. 2003;47(2):112–120.
  10. 10. Strayer RJ, Gunnerson JM, Brown LH, et al. Aortic dissection: clinical features, diagnosis, and management. Aust Crit Care. 2019;32(2):144–153.
  11. 11. Ombregt L. A system of orthopaedic medicine. 3rd edn. Edinburgh: Churchill Livingstone Elsevier; 2013. Chapter 18: Thoracic spine.
  12. 12. Lin CC, Chen KH, Li DM, et al. Characteristics and outcomes of patients presenting with thoracic back pain to the emergency department. Emerg Med Australas. 2020;32(5):805–811.
for PBS-listed medicines at participating pharmacies.
Cultural safety
Engagement with Aboriginal Community Controlled Health Organisations (ACCHOs) is essential. Cultural safety training for non-Indigenous clinicians, use of Aboriginal Health Workers and Liaison Officers, and incorporation of traditional healing practices alongside Western medicine improve treatment adherence and outcomes. Avoidance of eye contact, respect for gender-sensitive examination practices, and understanding of sorry business protocols are critical elements of culturally safe care.
Medication adherence
Complex DMARD regimens with frequent monitoring requirements present adherence challenges. Long-acting depot injections (e.g., methotrexate SC) may improve adherence compared to oral regimens. Community pharmacy partnerships through the Indigenous Pharmacy Programmes improve medication management.
Specific conditions
Rheumatic heart disease (RHD) requires secondary prophylaxis with benzathine penicillin G (BPG) 1.2 MU IM every 3–4 weeks for a minimum of 10 years or until age 21 (whichever is longer). RHD registers (e.g., NT RHD Register) facilitate recall and follow-up. The Australian RHD Endgame Strategy targets elimination by 2031.
Referral pathways
Referral through ACCHOs and Aboriginal Hospital Liaison Officers (AHLOs) improves engagement. The Specialist Outreach Assistance Programme provides funded specialist visits to remote communities. NT, WA, and QLD have specific rheumatology outreach programmes targeting Indigenous communities.

📚 References

  1. 1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
  2. 2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
  3. 3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
  4. 4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
  5. 5. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.
  6. 6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
  7. 7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
  8. 8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
  9. 9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
  10. 10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
  11. 11. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771–1782.
  12. 12. Ledingham J, Deighton C; British Society for Rheumatology Standards, Audit and Guidelines Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis. Rheumatology. 2005;44(2):155–158.
  13. 13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).
for PBS-listed medicines at participating pharmacies.
Cultural safety
Engagement with Aboriginal Community Controlled Health Organisations (ACCHOs) is essential. Cultural safety training for non-Indigenous clinicians, use of Aboriginal Health Workers and Liaison Officers, and incorporation of traditional healing practices alongside Western medicine improve treatment adherence and outcomes. Avoidance of eye contact, respect for gender-sensitive examination practices, and understanding of sorry business protocols are critical elements of culturally safe care.
Medication adherence
Complex DMARD regimens with frequent monitoring requirements present adherence challenges. Long-acting depot injections (e.g., methotrexate SC) may improve adherence compared to oral regimens. Community pharmacy partnerships through the Indigenous Pharmacy Programmes improve medication management.
Specific conditions
Rheumatic heart disease (RHD) requires secondary prophylaxis with benzathine penicillin G (BPG) 1.2 MU IM every 3–4 weeks for a minimum of 10 years or until age 21 (whichever is longer). RHD registers (e.g., NT RHD Register) facilitate recall and follow-up. The Australian RHD Endgame Strategy targets elimination by 2031.
Referral pathways
Referral through ACCHOs and Aboriginal Hospital Liaison Officers (AHLOs) improves engagement. The Specialist Outreach Assistance Programme provides funded specialist visits to remote communities. NT, WA, and QLD have specific rheumatology outreach programmes targeting Indigenous communities.

📚 References

  1. 1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
  2. 2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
  3. 3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
  4. 4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
  5. 5. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.
  6. 6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
  7. 7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
  8. 8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
  9. 9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
  10. 10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
  11. 11. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771–1782.
  12. 12. Ledingham J, Deighton C; British Society for Rheumatology Standards, Audit and Guidelines Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis. Rheumatology. 2005;44(2):155–158.
  13. 13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).