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Pain Medicine · NICE

Neuropathic pain

NICE
A
Source: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)
Verified Apr 2026
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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

DrugClassAdultPaediatricNotes
Amitriptyline[1]Tricyclic antidepressant10–25 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]Gabapentinoid75 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 / SNRI50–100 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

  1. Allow at least 4–8 weeks of treatment at adequate dose before judging effectiveness; gradual titration reduces side effects[1]
  2. Avoid alcohol — worsens neuropathic pain and interacts with most neuropathic medications[1]
  3. 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. 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)

On this page

  • Red flags
  • First-line treatment
  • Safety-net
  • Referral
  • References