Neuropathic pain
Pain from somatosensory nervous system damage or dysfunction. Burning, shooting pain, paresthesia, and allodynia are characteristic. Therapy: anticonvulsants (gabapentinoids), antidepressants (duloxetine, amitriptyline); topical lidocaine or capsaicin when systemic agents fail.
ICD-10 M79.25 drugs
Also known as: Nerve pain
Drugs used for this condition
- AAmitriptylineFirst line · Tricyclic antidepressants (TCA)First-line for neuropathic pain: NeuPSIG 2025 gives tricyclic antidepressants a strong recommendation alongside gabapentinoids and SNRIs (NNT 4.6), and NICE CG173 offers amitriptyline as one of four initial options to choose from. The exception is trigeminal neuralgia, where carbamazepine comes first. In Spain the indication is licensed (Tryptizol SmPC, section 4.1), and the EU harmonised it in a 2017 EMA decision. Start with 10–25 mg at bedtime and increase by 10–25 mg every 3–7 days up to 25–75 mg; a single dose above 75 mg is not recommended, and the analgesic effect usually appears within 2–4 weeks. Per Cochrane 2015 the individual RCTs are of low quality, only a minority of patients get substantial relief, and at least one adverse event occurs in 55% versus 36% on placebo. Contraindicated after a recent myocardial infarction, with heart block or arrhythmia, coronary insufficiency, severe liver disease and together with MAOIs. Use with caution in QT prolongation, angle-closure glaucoma, urinary retention and epilepsy. Over age 65 and in heart disease start with 10–25 mg and use doses above 75 mg with caution; the AGS Beers Criteria 2023 advise older adults to avoid amitriptyline because of its anticholinergic effects and orthostatic hypotension. In patients under 25, antidepressants raise the risk of suicidal behaviour. Tramadol raises the risk of seizures and serotonin syndrome; fluoxetine, paroxetine and bupropion raise amitriptyline levels. An adult dose of 750 mg or more can cause severe poisoning. In pregnancy only when clearly needed; 0.6–1% of the maternal dose passes into breast milk.
- AGabapentinFirst line · Gabapentinoids (antiepileptics)First-line for neuropathic pain per NeuPSIG 2015 and IASP 2022. Used in diabetic polyneuropathy, post-herpetic neuralgia, and trigeminal neuralgia. Start 300 mg at bedtime, titrate to 900–3600 mg/day in three divided doses. Effect develops over 2–4 weeks. NNT for PHN – 7; for diabetic neuropathy – 6.
- APregabalinFirst line · Gabapentinoids (antiepileptics)First-line for neuropathic pain per NeuPSIG 2015 and IASP 2022. Used in diabetic polyneuropathy, post-herpetic neuralgia, and spinal pain. Start 75 mg twice daily; titrate to 150–300 mg twice daily. Max 600 mg/day. Onset over 1–2 weeks. Pregabalin carries a potential for misuse and dependence with a withdrawal syndrome; it is a controlled substance in several countries (UK Class C since 2019), so taper the dose gradually.
- BTramadolSecond line · Other opioidsPer NeuPSIG 2015 and IASP 2022, tramadol is second-line for neuropathic pain after gabapentinoids, SNRIs (duloxetine, venlafaxine), and tricyclic antidepressants. Use is restricted to short courses due to dependence risk. In diabetic polyneuropathy, tramadol may serve as an episodic agent during flares.
- CPalmitoylethanolamideAdd-on therapy · Endogenous fatty-acid amide (aliamide); in Italy and Spain registered as a complemento alimenticio and «specialty food for medical purposes» for chronic neuropathic painPEA is an endogenous fatty-acid amide widely used in Italy and Spain for chronic neuropathic pain (sciatica, diabetic polyneuropathy, post-herpetic neuralgia, carpal tunnel, pelvic pain). The Paladini meta-analysis (Pain Physician 2016) pooled 12 RCTs and observational studies with 1484 participants: at 600–1200 mg/day for 30–60 days, PEA reduced VAS pain by a mean 1.8 points versus placebo or standard care. Effect size is small, confidence intervals wide and most studies are funded by the manufacturer Epitech. Cochrane opened a 2017 review protocol on PEA for chronic pain but withdrew it in 2018 without a full review – the Cochrane Library has no quality meta-analytic base. NICE CG173 for neuropathic pain recommends amitriptyline, duloxetine, gabapentin and pregabalin as first line; PEA is not in international guidelines. In Italy and Spain, neurologists and pain clinicians prescribe PEA off-label as adjunct therapy when first-line drugs are contraindicated. If PEA is being considered instead of pregabalin or duloxetine, discuss with a doctor – the first-line drugs have stronger evidence.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit