Neuropathic pain

Red Flags

Cauda equina syndrome (saddle anaesthesia, urinary retention, bilateral leg pain) — emergency MRI same-day; surgical decompression^[1]
Suspected secondary cause (malignancy, infection, demyelination, vasculitis, diabetic plexopathy with sudden onset) — investigate before chronic neuropathic pain pathway^[1]
Suicidality, severe self-harm, or substance use disorder developing on neuropathic pain medication — same-day mental health support^[1]
Severe activation, mood change, or worsening depression on TCA / SNRI / gabapentinoid in early weeks — review medication and monitor closely^[1]

First-line treatment

Interventions

Treat underlying cause where possible^[1]
Glycaemic control in diabetic neuropathy; vitamin B12 replacement; antiretrovirals for HIV neuropathy; VZV vaccination history for post-herpetic; surgical decompression for compressive lesions; chemotherapy adjustment for chemo-induced
Stepwise pharmacotherapy^[1]
First-line: amitriptyline, duloxetine, gabapentin, or pregabalin (any one). If first ineffective or not tolerated at adequate dose, switch to one of the others. Combine if partial response and tolerability allows
Adjunctive non-pharmacological^[1]
Cognitive behavioural therapy for chronic pain, mindfulness, exercise, physiotherapy, TENS (selected); occupational therapy; address sleep and mood; pain management programmes for refractory cases
Specialist pain medicine for refractory disease^[1]
Failure of three first-line agents at adequate dose and duration; consider cannabinoids (selected jurisdictions), interventional procedures (nerve blocks, neuromodulation, intrathecal therapy), botulinum toxin for selected pain types

First-line drug therapy

Drug	Class	Adult	Paediatric	Notes
Amitriptyline^[1]	Tricyclic antidepressant	10–25 mg PO at night start, titrate by 10–25 mg every 1–2 weeks to 75 mg/day max in pain	—	Effective for neuropathic pain and comorbid insomnia; anticholinergic effects (dry mouth, urinary retention, constipation, glaucoma); ECG before higher doses in cardiac comorbidity
Duloxetine^[1]	Serotonin-norepinephrine reuptake inhibitor (SNRI)	30 mg PO daily start, titrate to 60–120 mg daily	—	First-line especially with comorbid depression or anxiety; nausea on initiation; hepatic caution; avoid with MAOI and severe renal impairment
Gabapentin^[1]	Gabapentinoid (α2δ ligand)	300 mg PO night × 3 days, then 300 mg BD × 3 days, then 300 mg TDS; usual 900–3600 mg/day in three divided doses	—	First-line; lower cost than pregabalin; renal dose adjustment; sedation, dizziness, peripheral oedema common
Pregabalin^[1]	Gabapentinoid	75 mg PO BD start, titrate to 150–300 mg BD as tolerated	—	First-line; weight gain, sedation, peripheral oedema; renal dose adjustment; misuse potential — controlled in some jurisdictions
Topical capsaicin 8% patch^[1]	TRPV1 agonist (topical)	Single 30-min application to affected area; can repeat every 90 days	—	Localised peripheral neuropathic pain (post-herpetic, diabetic localised); transient burning at application site; pre-treat with topical anaesthetic; specialist application
Topical lidocaine 5% patch^[1]	Sodium channel blocker (topical)	Up to 3 patches applied to most painful area for up to 12 h/24 h	—	Localised neuropathic pain (post-herpetic neuralgia); minimal systemic absorption; safer in elderly with comorbidities
Tramadol (selected, short-term)^[1]	Atypical opioid / SNRI	50–100 mg PO every 4–6 h, max 400 mg/day	—	Reserve for severe refractory pain; risk of serotonin syndrome with serotonergic agents; dependence; avoid long-term and in elderly with falls risk

Amitriptyline^[1]

Tricyclic antidepressant

Adult: 10–25 mg PO at night start, titrate by 10–25 mg every 1–2 weeks to 75 mg/day max in pain
Paediatric: —

Effective for neuropathic pain and comorbid insomnia; anticholinergic effects (dry mouth, urinary retention, constipation, glaucoma); ECG before higher doses in cardiac comorbidity

Duloxetine^[1]

Serotonin-norepinephrine reuptake inhibitor (SNRI)

Adult: 30 mg PO daily start, titrate to 60–120 mg daily
Paediatric: —

First-line especially with comorbid depression or anxiety; nausea on initiation; hepatic caution; avoid with MAOI and severe renal impairment

Gabapentin^[1]

Gabapentinoid (α2δ ligand)

Adult: 300 mg PO night × 3 days, then 300 mg BD × 3 days, then 300 mg TDS; usual 900–3600 mg/day in three divided doses
Paediatric: —

First-line; lower cost than pregabalin; renal dose adjustment; sedation, dizziness, peripheral oedema common

Pregabalin^[1]

Gabapentinoid

Adult: 75 mg PO BD start, titrate to 150–300 mg BD as tolerated
Paediatric: —

First-line; weight gain, sedation, peripheral oedema; renal dose adjustment; misuse potential — controlled in some jurisdictions

Topical capsaicin 8% patch^[1]

TRPV1 agonist (topical)

Adult: Single 30-min application to affected area; can repeat every 90 days
Paediatric: —

Localised peripheral neuropathic pain (post-herpetic, diabetic localised); transient burning at application site; pre-treat with topical anaesthetic; specialist application

Topical lidocaine 5% patch^[1]

Sodium channel blocker (topical)

Adult: Up to 3 patches applied to most painful area for up to 12 h/24 h
Paediatric: —

Localised neuropathic pain (post-herpetic neuralgia); minimal systemic absorption; safer in elderly with comorbidities

Tramadol (selected, short-term)^[1]

Atypical opioid / SNRI

Adult: 50–100 mg PO every 4–6 h, max 400 mg/day
Paediatric: —

Reserve for severe refractory pain; risk of serotonin syndrome with serotonergic agents; dependence; avoid long-term and in elderly with falls risk

Safety-net

Allow at least 4–8 weeks of treatment at adequate dose before judging effectiveness; gradual titration reduces side effects^[1]
Avoid alcohol — worsens neuropathic pain and interacts with most neuropathic medications^[1]
Tell every healthcare worker about your neuropathic pain medications — interactions matter for analgesia, surgery, and other prescriptions^[1]

Referral criteria

Failure of two or three adequate first-line trials at maximum tolerated doseSpecialist pain medicine clinic^[1]
Severe disability, suicidality, or substance use complicating painMultidisciplinary pain service with psychology and psychiatry input^[1]
Suspected secondary cause requiring further workup or interventional managementNeurology / relevant subspecialty^[1]
Pregnancy or planning pregnancy on neuropathic pain medicationJoint pain medicine and obstetric clinic — many agents contraindicated^[1]

Clinical summary

Stepwise pharmacological and non-pharmacological management of neuropathic pain in adults including diabetic, post-herpetic, and post-surgical aetiologies.

References

1.NICE Clinical Guideline CG173 — Neuropathic Pain in Adults: Pharmacological Management in Non-Specialist Settings (2013, updated 2020); IASP Special Interest Group on Neuropathic Pain (2020)